| 2021 | Atypical presentation of autoimmune polyglandular syndrome type 1 in the fifth decade. | BMJ Case Rep | A 45-year-old woman presented to us with a short-term history of nausea, vomiting and giddiness. On arrival at our hospital, examination revealed postural hypotension. Fluid resuscitation with intravenous normal saline was commenced. She also had chronic mucocutaneous candidiasis and nail changes suggestive of ectodermal dystrophy. Detailed history taking revealed that she had never attained menarche. Serum biochemistries showed hyponatraemia, hyperkalaemia, and hypocalcaemia (sodium, 127 mEq/L; potassium, 6 mEq/L; and albumin-corrected calcium, 6 mg/dL). Adrenocorticotropic hormone-stimulated cortisol (16.7 mcg/dL) was suboptimal favouring adrenal insufficiency. She was started on hydrocortisone and fludrocortisone supplementation. Additionally, the parathyroid hormone was inappropriately low (3.8 pg/mL) confirming hypoparathyroidism. Oral calcium and active vitamin D supplementation were added. With the above clinical and biochemical picture, namely, clustering of primary amenorrhoea, adrenal insufficiency and hypoparathyroidism, the diagnosis pointed towards autoimmune polyglandular syndrome. Genetic workup revealed a deletion in exon 8 of the autoimmune regulator gene confirming the diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy/autoimmune polyglandular syndrome type 1 . |
| 2021 | Effects of high-flux hemodialysis combined with levocarnitine on vascular calcification, microinflammation, hepcidin, and malnutrition of elderly patients on maintenance hemodialysis. | Ann Palliat Med | This study was to investigate the effect of high-flux hemodialysis (HD) combined with levocarnitine on vascular calcification, microinflammation, hepcidin, and malnutrition in elderly patients on maintenance HD (MHD).75 MHD elderly patients admitted to hospital between 1st September 2017 and 31st August 2019 were selected as the study subjects. They were randomly divided by digital table into three groups: low-flux group (n=25), high-flux group (n=25) and joint group (n=25). In the low-flux group, dialyzer had an ultrafiltration coefficient 12 mL/(h·mmHg) and effective surface area of 1.4 m2 compared with 59 mL/(h·mmHg) and 1.8 m2 in the high-flux group. After treatment, the calcification of blood vessels was examined by lateral X-ray, pelvic plain film and bilateral positive position. For patients in all groups, the concentrations of parathyroid hormone (PTH) and β 2-microglobulin (β 2-MG) in serum were measured by automatic chemiluminescence; levels of interleukin-6, C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α) were measured by ELISA before and after treatment; and the level of hepcidin was measured by ELISA. Before and 12 weeks after the treatment, the nutritional status of the patients was evaluated by modified quantitative subjective global assessment (MQSGA), hemoglobin (Hb) and red blood cell count (RBC). Complications in the three groups were recorded, including nausea, chest pain, hypotension, hypertension, pruritus, dry heat, muscle spasm, arrhythmia, and restless legs.Vascular calcification in the joint group was better than the low-flux and high-flux groups (P<0.05). After treatment, the serum PTH and β 2-mg concentrations in the joint group were lower than those in the other two groups (P<0.05), and the levels of IL-6, CRP, TNF-α and hepcidin in the joint group were significantly lower than those before treatment (P<0.05). After treatment, the MQSGA scores in the joint group were lower than those in the low-flux and high-flux groups (P<0.05), and Hb and RBC were higher (P<0.05).The combination of high-flux HD and levocarnitine in elderly patients on MHD can increase the clearance of medium and large molecular toxins, effectively correct malnutrition, alleviate microinflammation, delay the progress of vascular calcification, and is safe. |
| 2021 | Vitamin D deficiency is associated with orthostatic hypotension in older men: a cross-sectional analysis from the British Regional Heart Study. | Age Ageing | orthostatic hypotension (OH) that occurs within, or at, 1 minute of standing is associated with higher risk of falls, myocardial infarction, syncope and mortality, compared to OH that occurs after 1 minute of standing. Whether vitamin D deficiency increases the risk of OH is controversial.this was a cross-sectional analysis of 3,620 older, community-dwelling men. Multinomial, multiple logistic regression models were used to calculate the risk of OH across categories of vitamin D status (deficient [<25 nmol/l], insufficient [≥25-<50 nmol/l] and sufficient [≥50 nmol/l]) and parathyroid hormone quintile.men with vitamin D deficiency were more likely to have OH that occurred within 1 minute of standing in univariate logistic regression (OR 1.88, 95% CI 1.40-2.53) and multinomial, multiple logistic regression (OR 1.51, 95% CI 1.06-2.15), compared to men with sufficient levels of vitamin D. Vitamin D insufficiency was not associated with the risk of OH. Elevated parathyroid hormone was not associated with risk of OH.the absence of an association between vitamin D insufficiency and risk of OH and the presence of an association between vitamin D deficiency and risk of OH suggest that there may be a threshold effect; it is only below a particular level of vitamin D that risk of OH is increased. In this cohort, the threshold was <25 nmol/l. Future work should investigate whether treating vitamin D deficiency can improve postural blood pressure or if preventing vitamin D deficiency reduces the incidence of OH. |
| 2020 | Vitamin D deficiency is associated with increased risk of postural hypotension in older men: a cross-sectional analysis from The British Regional Heart Study. | Br J Gen Pract | There is growing interest in the role of vitamin D in extra-skeletal health, including postural hypotension. Postural hypotension is found in 1 in 5 community-dwelling adults aged 60 years and above. It increases risk of falls, fractures, cardiovascular disease and all-cause mortality. Better understanding of the aetiology of postural hypotension may help yield more effective treatment options than those that are currently available.The aim of this study was to investigate the association between circulating vitamin D, parathyroid hormone and postural hypotension.This was a cross-sectional analysis of 3620 community-dwelling men living in the UK (mean age 68.6 years; standard deviation 5.5 years). Vitamin D status (nmol/L) was categorised as sufficient (≥50), insufficient (≥25 - <50), or deficient (<25). Parathyroid hormone levels were categorised by quintiles. Postural hypotension was defined by consensus criteria as a decrease in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg that occurred within three minutes of standing.Compared to sufficient levels of vitamin D, vitamin D deficiency increased risk of postural hypotension that specifically occurred within one minute of standing (OR 1.51, 95% CI = 1.06 to 2.15) in multinomial, multiple logistic regression. Neither vitamin D insufficiency, nor elevated parathyroid hormone, were associated with postural hypotension.In this study, vitamin D deficiency was associated with increased risk of postural hypotension. Further research may help clarify whether treating vitamin D deficiency can reduce the degree of postural hypotension, or if preventing the progression to vitamin D deficiency can reduce the incidence of postural hypotension. |
| 2020 | Impact of Weekly Teriparatide on the Bone and Mineral Metabolism in Hemodialysis Patients With Relatively Low Serum Parathyroid Hormone: A Pilot Study. | Ther Apher Dial | Adynamic bone disease in HD patients is characterized by skeletal resistance to parathyroid hormone (PTH) or suppression of PTH release, leading to a downregulated bone turnover and bone fracture. Hence, we examined the efficacy of weekly teriparatide for HD patients with low PTH indicating adynamic bone disease without a history of parathyroidectomy. Fifteen HD patients with low PTH were recruited in this prospective observational study. Of them, 10 received teriparatide for 12 months and five nontreated patients were enrolled as control. Primary outcomes were defined as the changes in bone mineral density and bone turnover markers. Bone mineral density at the lumbar spine increased by 3.7% and 2.5% at 6 and 12 months, respectively, and bone formation markers increased, while bone resorption markers did not change in the teriparatide group. At 12 months after teriparatide administration, endogenous PTH was secreted followed by the recovery of low bone turnover. 40% of patients in the teriparatide group dropped out due to adverse events and the most common adverse event was transient hypotension. This study suggests that weekly teriparatide for HD patients with low PTH in the absence of parathyroidectomy accelerates bone formation and bone turnover, leading to increased trabecular bone mass and secretion of endogenous PTH. |
| 2019 | General anesthesia for patient with Fahr's syndrome: A case report. | Medicine (Baltimore) | Fahr's syndrome (FS) is a rare neurological and psychiatric disorder characterized by bilateral brain calcifications when a secondary cause of the calcification is found.A 53-year-old female patient diagnosed with FS for laminectomy because of ossification of posterior longitudinal ligament. She had a history of generalized tonic-clonic (GTC) seizure and medication with anticonvulsant drugs. She had gait disturbance, spasticity, bradykinesia, and diffuse calcifications in the basal ganglia, thalamus, cerebellum, and cerebral hemispheres on the brain computed tomography. On the preoperative examination, the serum and ionized calcium (Ca) were decreased to 3.7 and 2.22 mg/dL. Hypomagnesemia is combined with hypocalcemia. Furthermore, the level of parathyroid hormone was decreased to 2.18 pg/mL.Due to the radiologic findings and laboratory test results, she was diagnosed with FS with primary hypoparathyroidism.The Ca and magnesium (Mg) had been corrected before surgery but the electrolytes revealed low level at the intraoperative period. The 300 mg of calcium chloride was administered at 2 times and 1200 mg of it were infused for 1 hour during intraoperative periods. In addition, total 4 g of Mg sulfate intravenously administered. We used rocuronium as a neuromuscular block and checked neuromuscular function by train-of-four monitoring.Residual neuromuscular blockade was reversed with pyridostigmine and her muscle power completely recovered. The patient was extubated successfully and no unpredictable events occurred. On the day following transfer, serum electrolytes remained low, and although Ca was continuously supplied, serum Ca did not recover to a normal level. The patient was medicated with anticonvulsant drugs but experienced GTC seizure 2 weeks after surgery.We presume that the pathophysiology of FS was related to primary hypoparathyroidism and hypomagnesemia. FS raises concerns associated with neuromuscular problems, spasticity, and seizure, and concerns of hypotension, heart failure, cardiac arrhythmia, and cerebrovascular attack during perioperative periods, among anesthesiologists because of hypocalcemia and vessel calcification. During the perioperative period, Ca levels should be closely monitored, and titrated Ca replacement therapy is recommended. The simultaneous correction of hypomagnesemia is of considerable importance when correcting hypocalcemia. |
| 2019 | Orthostatic Hypotension in Asymptomatic Patients with Chronic Kidney Disease. | Medicina (Kaunas) | : Orthostatic hypotension (OH) is a decrease in systolic blood pressure (BP) of 20 mm Hg and in diastolic BP of 10 mm Hg when changing the position from lying to standing. Arterial hypertension (AH), comorbidities and polypharmacy contribute to its development. The aim was to assess the presence of OH and its predictors in asymptomatic chronic kidney disease (CKD) patients. : 45 CKD patients with estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m (CKD+) were examined for signs of OH and its predictors. The results were compared with the control group of 22 patients with eGFR > 60 mL/min/1.73 m (CKD-). Asymptomatic patients without ischemic heart disease and previous stroke were qualified. Total blood count, serum creatinine, eGFR, urea, phosphates, calcium, albumins, parathyroid hormone, uric acid, C reactive protein, N-terminal pro b-type natriuretic peptide, lipid profile, and urine protein to creatinine ratio were assessed. Simultaneously, patients underwent echocardiography. To detect OH, a modified Schellong test was performed. : OH was diagnosed in 17 out of 45 CKD+ patients (average age 69.12 ± 13.2) and in 8 out of 22 CKD- patients (average age 60.50 ± 14.99). The CKD+ group demonstrated significant differences on average values of systolic and diastolic BP between OH+ and OH- patients, lower when standing. In the eGFR range of 30-60 mL/min/1.73 m correlation was revealed between OH and β-blockers ( = 0.04), in the entire CKD+ group between β-blockers combined with diuretics ( = 0.007) and ACE-I ( = 0.033). Logistic regression test revealed that chronic heart failure (CHF, OR = 15.31), treatment with β-blockers (OR = 13.86) were significant factors influencing the presence of OH. : Predictors of OH in CKD may include: CHF, treatment with β-blockers, combined with ACE-I and diuretics. |
| 2019 | Predicting intradialytic hypotension using heart rate variability. | Sci Rep | This study aimed to identify whether a new method using heart rate variability (HRV) could predict intradialytic hypotension (IDH) for one month in advance for patients undergoing prevalent hemodialysis. A total 71 patients were enrolled, and baseline clinical characteristics and laboratory results were collected when HRV was measured, then, the frequency of IDH was collected during the observation period. HRV parameters included heart rate, R-R interval, the standard deviation of N-N interval, the square root of the mean squared differences of successive NN intervals, very low frequency, low frequency, high frequency, total power, and low frequency/high frequency ratio. During the one-month observation period, 28 patients experienced 85 cases of IDH (10.0% of a total 852 dialysis sessions). Among the clinical and laboratory parameters, ultrafiltration rate, prior history of diabetes, coronary artery disease, or congestive heart failure, age, intact parathyroid hormone level, and history of antihypertensive drug use were integrated into the multivariate model, referred to as a basic model, which showed significant ability to predict IDH (the area-under-curve [AUC], 0.726; p = 0.002). In HRV parameters, changes between the early and middle phases of hemodialysis (referred to Δ) were identified as significant independent variables. New models were built from the combination of Δ values with the basic model. Among them, a model with the highest AUC value (AUC, 804; p < 0.001) was compared to the basic model and demonstrated improved performance when HRV parameters were used (p = 0.049). Based on our results, it is possible that future IDH might be predicted more accurately using HRV. |
| Prospective randomised multicentre study to demonstrate the benefits of haemodialysis without acetate (with citrate): ABC-treat Study. Acute effect of citrate. | Nefrologia (Engl Ed) | Dialysis fluid (DF), an essential element in hemodialysis (HD), is manufactured in situ by mixing three components: treated water, bicarbonate concentrate and acid concentrate. To avoid the precipitation of calcium and magnesium carbonate that is produced in DF by the addition of bicarbonate, it is necessary to add an acid. There are 2 acid concentrates that contain acetate (ADF) or citrate (CDF) as a stabilizer.To compare the acute effect of HD with CDF vs. ADF on the metabolism of calcium, phosphorus and magnesium, acid base balance, coagulation, inflammation and hemodynamic stability.Prospective, multicenter, randomized and crossed study, of 32 weeks duration, in patients in three-week HD, AK-200-Ultra-S or Artis monitor, 16 weeks with ADF SoftPac, prepared with 3mmol/L of acetate, and 16 weeks with CDF SelectBag Citrate, with 1mmol/L of citrate. Patients older than 18 years were included in HD for a minimum of 3 months by arteriovenous fistula. Epidemiological, dialysis, pre and postdialysis biochemistry, episodes of arterial hypotension, and coagulation scores were collected monthly during the 8 months of the study. Pre and post-dialysis analysis were extracted: venous blood gas, calcium (Ca), ionic calcium (Cai), phosphorus (P), magnesium (Mg) and parathyroid hormone (PTH) among others. ClinicalTrials.gov NCT03319680.We included 56 patients, 47 (84%) men and 9 (16%) women, mean age: 65.3 (16.4) years, technique HD/HDF: 20 (35.7%)/36 (64.3%). We found differences (p<0.05) when using the DF with citrate (C) versus acetate (A) in the postdialysis values of bicarbonate [C: 26.9 (1.9) vs. A: 28.5 (3) mmol/L], Cai [C: 1.1 (0.05) vs. A: 1.2 (0.08) mmol/L], Mg [C: 1.8 (0.1) vs A: 1, 9 (0.2) mg/dL] and PTH [C: 255 (172) vs. 148 (149) pg/mL]. We did not find any differences in any of the parameters measured before dialysis. Of the 4,416 sessions performed, 2,208 in each group, 311 sessions (14.1%) with ADF and 238 (10.8%) with CDF (p<0.01), were complicated by arterial hypotension. The decrease in maximum blood volume measured by Hemoscan biosensor was also lower [-3.4 (7.7) vs -5.1 (8.2)] although without statistical significance.Dialysis with citrate acutely produces less postdialysis alkalemia and significantly modifies Ca, Mg and PTH. CDF has a positive impact on hemodynamic tolerance. |
| 2018 | Effect of Sodium-Glucose Co-transporter 2 Inhibitors on Bone Metabolism and Fracture Risk. | Front Pharmacol | The effect of anti-diabetic medications on bone metabolism has received increasing attention, considering that type 2 diabetes mellitus is a common metabolic disorder with adverse effects on bone metabolism. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel anti-diabetic medications that prevent glucose resorption at the proximal convoluted tubules in the kidney, increasing urinary glucose excretion, and decreasing the blood glucose level. The superiority of SGLT2 inhibitors shows in reducing the glucose level independent of insulin secretion, lowering the risk of hypoglycemia, and improving cardiovascular outcomes. SGLT2 inhibitors have been associated with genital mycotic infections, increased risk of acute kidney injury, dehydration, orthostatic hypotension, and ketoacidosis. Moreover, the effect of SGLT2 inhibitors on bone metabolism and fracture risk has been widely taken into consideration. Our review summarizes the results of current studies investigating the effects of SGLT2 inhibitors on bone metabolism (possibly including increased bone turnover, disrupted bone microarchitecture, and reduced bone mineral density). Several mechanisms are probably involved, such as bone mineral losses due to the disturbed calcium and phosphate homeostasis, as confirmed by an increase in fibroblast growth factor 23 and parathyroid hormone levels and a decrease in 1,25-dihydroxyvitamin D levels. SGLT2 inhibitors might indirectly increase bone turnover by weight loss. Lowering the blood glucose level might ameliorate bone metabolism impairment in diabetes. The effect of SGLT2 inhibitors on bone fractures remains unclear. Evidence indicating the direct effect of SGLT2 inhibitors on fracture risk is lacking and increased falls probably contribute to fractures. |
| 2018 | Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial. | Am J Nephrol | The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder.CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements.Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group.L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006). |
| 2018 | Prescribing Hemodialysis or Hemodiafiltration: When One Size Does Not Fit All the Proposal of a Personalized Approach Based on Comorbidity and Nutritional Status. | J Clin Med | There is no simple way to prescribe hemodialysis. Changes in the dialysis population, improvements in dialysis techniques, and different attitudes towards the initiation of dialysis have influenced treatment goals and, consequently, dialysis prescription. However, in clinical practice prescription of dialysis still often follows a "one size fits all" rule, and there is no agreed distinction between treatment goals for the younger, lower-risk population, and for older, high comorbidity patients. In the younger dialysis population, efficiency is our main goal, as assessed by the demonstrated close relationship between depuration (tested by kinetic adequacy) and survival. In the ageing dialysis population, tolerance is probably a better objective: "good dialysis" should allow the patient to attain a stable metabolic balance with minimal dialysis-related morbidity. We would like therefore to open the discussion on a personalized approach to dialysis prescription, focused on efficiency in younger patients and on tolerance in older ones, based on life expectancy, comorbidity, residual kidney function, and nutritional status, with particular attention placed on elderly, high-comorbidity populations, such as the ones presently treated in most European centers. Prescription of dialysis includes reaching decisions on the following elements: dialysis modality (hemodialysis (HD) or hemodiafiltration (HDF)); type of membrane (permeability, surface); and the frequency and duration of sessions. Blood and dialysate flow, anticoagulation, and reinfusion (in HDF) are also briefly discussed. The approach described in this concept paper was developed considering the following items: nutritional markers and integrated scores (albumin, pre-albumin, cholesterol; body size, Body Mass Index (BMI), Malnutrition Inflammation Score (MIS), and Subjective Global Assessment (SGA)); life expectancy (age, comorbidity (Charlson Index), and dialysis vintage); kinetic goals (Kt/V, normalized protein catabolic rate (n-PCR), calcium phosphate, parathyroid hormone (PTH), beta-2 microglobulin); technical aspects including vascular access (fistula versus catheter, degree of functionality); residual kidney function and weight gain; and dialysis tolerance (intradialytic hypotension, post-dialysis fatigue, and subjective evaluation of the effect of dialysis on quality of life). In the era of personalized medicine, we hope the approach described in this concept paper, which requires validation but has the merit of providing innovation, may be a first step towards raising attention on this issue and will be of help in guiding dialysis choices that exploit the extraordinary potential of the present dialysis "menu". |
| 2018 | Theoretical overview of clinical and pharmacological aspects of the use of etelcalcetide in diabetic patients undergoing hemodialysis. | Drug Des Devel Ther | Etelcalcetide is the first intravenous calcimimetic agent authorized for the treatment of secondary hyperparathyroidism (sHPT) in patients undergoing hemodialysis in Europe, the US, and Japan. The relationship between sHPT and diabetes resides on complex, bidirectional effects and largely unknown homeostatic mechanisms. Although 30% or more patients with end-stage renal disease are diabetics and about the same percentage of those patients suffer from sHPT associated with hemodialysis, no data on the specificities of the use of etelcalcetide in such patients are available yet. Regarding pharmacokinetic interactions, etelcalcetide may compete with oral hypoglycemics recommended for use in patients undergoing hemodialysis and insulins detemir and degludec, causing unexpected hypocalcemia or hypoglycemia. More importantly, hypocalcemia, a common side effect of etelcalcetide, may cause decompensation of preexisting cardiac insufficiency in diabetic patients or worsen dialysis-related hypotension and lead to hypotension-related cardiac events, such as myocardial ischemia. In diabetic patients, hypocalcemia may lead to dangerous ventricular arrhythmias, as both insulin-related hypoglycemia and hemodialysis prolong QT interval. Patients with diabetes, therefore, should be strictly monitored for hypocalcemia and associated effects. Due to an altered parathormone activity in this patient group, plasma calcium should be the preferred indicator of etelcalcetide effects. Until more clinical experience with etelcalcetide is available, the clinicians should be cautious when using this calcimimetic in patients with diabetes. |
| 2017 | Vitamin D and the Mechanisms, Circumstances and Consequences of Falls in Older Adults: A Case-Control Study. | J Nutr Health Aging | To determine i) whether cases of elderly fallers had lower serum 25-hydroxyvitamin D (25OHD) concentration than controls without history of falls; and ii) whether serum 25OHD concentration was associated with specific mechanisms, circumstances and consequences of falls.Case-control study with a 1:2 ratio.Geriatric ward of the University Hospital of Angers, France, between February 2012 and March 2014.216 inpatients (72 cases and 144 age- and gender-matched controls).Falls were defined as involuntary events causing the person to the ground or other lower level. The main mechanisms, circumstances and consequences of falls were identified using standardized questionnaires. Vitamin D deficiency was defined as serum 25OHD concentration ≤25nmol/L. Age, gender, body mass index, polypharmacy, use antihypertensive drugs, use psychoactive drugs, disability, cognitive performance, serum concentrations of parathyroid hormone, creatinine and albumin, and season of evaluation were used as potential confounders.216 participants (72 cases and 144 controls) were included in the study. There was no between-group difference in the prevalence of vitamin D deficiency (P=0.176). After adjusting for confounding factors, vitamin D deficiency was positively associated with falls (OR=4.03, P=0.014). Finally, the fallers with vitamin D deficiency exhibited more often orthostatic hypotension (68.8% against 33.3%, P=0.039) and a history of recurrent falls (85% against 50%, P=0.002) than those without vitamin D deficiency.This case-control study reported that vitamin D deficiency was associated with falls in older inpatients. There was a greater prevalence of orthostatic hypotension and of the reccurrence of falls among fallers with vitamin D deficiency, suggesting that vitamin D may influence the conditions predisposing to falls rather than the fall by itself. |
| 2017 | Pneumatic Compression, But Not Exercise, Can Avoid Intradialytic Hypotension: A Randomized Trial. | Am J Nephrol | Conventional hemodialysis (HD) is associated with dialysis-induced hypotension (DIH) and ineffective phosphate removal. As the main source of extracellular fluid removed during HD are the legs, we sought to reduce DIH and increase phosphate removal by using cycling and pneumatic compression, which would potentially provide higher venous return, preserving central blood flow and also offering more phosphate to the dialyzer.We evaluated 21 patients in a randomized crossover fashion in which each patient underwent 3 different HD: control; cycling exercise during the first 60 min; and pneumatic compression during the first 60 min. Data obtained included bioelectrical impedance, hourly blood pressure measurement, biochemical parameters, and direct quantification of phosphate through the dialysate. DIH was defined as a drop in mean arterial pressure (MAP) ≥20 mm Hg.There was no difference in the ultrafiltration rate (p = 0.628), delta weight (p = 0.415), delta of total, intra and extracellular body water among the control, cycling, and pneumatic compression (p = 0.209, p = 0.348, and p = 0.467 respectively). Delta MAP was less changed by pneumatic compression when compared to control, cycling, and pneumatic compression respectively (-4.7 [-17.2, 8.2], -4.7 [-20.5, -0.2], and -2.3 [-8.1, 9.0] mm Hg; p = 0.021). DIH occurred in 43, 38, and 24% of patients in control, cycling, and pneumatic compression respectively (p = 0.014). Phosphate removal did not increase in any intervention (p = 0.486). Higher phosphate removal was dependent on ultrafiltration, pre dialysis serum phosphate, and higher parathyroid hormone.Pneumatic compression during the first hour of dialysis was associated with less DIH, albeit there was no effect on fluid parameters. Neither exercise nor pneumatic compression increased phosphate removal. |
| 2017 | Atherosclerotic Surrogate Markers in Adults With Down Syndrome: A Case-Control Study. | J Clin Hypertens (Greenwich) | The authors aimed to compare surrogate markers of atherosclerosis (pulse wave velocity, intima-media thickness) between adults with and without Down syndrome (DS) and to assess the impact of parathyroid hormone levels and classic cardiovascular risk factors on arterial stiffness. After comparing 51 adults with DS and 51 healthy adults (siblings of DS individuals), the authors found that adults with DS seem to have lower arterial stiffness, as a result of chronic hypotension. Subclinical atherosclerosis parameters do not correlate with traditional cardiovascular risk factors in adults with DS, thus raising the hypothesis that classic predictive models for cardiovascular disease are not valid in this population. Hyperparathyroidism could play an important role in arterial damage in these individuals. The lower than expected prevalence of obesity and dyslipidemia could be explained by better eating habits, with this study being the first to address the anthropometric and clinical profile of a Mediterranean cohort of adults with DS. |
| 2016 | Endothelial Restoration of Receptor Activity-Modifying Protein 2 Is Sufficient to Rescue Lethality, but Survivors Develop Dilated Cardiomyopathy. | Hypertension | RAMPs (receptor activity-modifying proteins) serve as oligomeric modulators for numerous G-protein-coupled receptors, yet elucidating the physiological relevance of these interactions remains complex. Ramp2 null mice are embryonic lethal, with cardiovascular developmental defects similar to those observed in mice null for canonical adrenomedullin/calcitonin receptor-like receptor signaling. We aimed to genetically rescue the Ramp2(-/-) lethality in order to further delineate the spatiotemporal requirements for RAMP2 function during development and thereby enable the elucidation of an expanded repertoire of RAMP2 functions with family B G-protein-coupled receptors in adult homeostasis. Endothelial-specific expression of Ramp2 under the VE-cadherin promoter resulted in the partial rescue of Ramp2(-/-) mice, demonstrating that endothelial expression of Ramp2 is necessary and sufficient for survival. The surviving Ramp2(-/-) Tg animals lived to adulthood and developed spontaneous hypotension and dilated cardiomyopathy, which was not observed in adult mice lacking calcitonin receptor-like receptor. Yet, the hearts of Ramp2(-/-) Tg animals displayed dysregulation of family B G-protein-coupled receptors, including parathyroid hormone and glucagon receptors, as well as their downstream signaling pathways. These data suggest a functional requirement for RAMP2 in the modulation of additional G-protein-coupled receptor pathways in vivo, which is critical for sustained cardiovascular homeostasis. The cardiovascular importance of RAMP2 extends beyond the endothelium and canonical adrenomedullin/calcitonin receptor-like receptor signaling, in which future studies could elucidate novel and pharmacologically tractable pathways for treating cardiovascular diseases. |
| 2015 | Facility Dialysate Calcium Practices and Clinical Outcomes Among Patients Receiving Hemodialysis: A Retrospective Observational Study. | Am J Kidney Dis | Some US dialysis facilities have reduced default dialysate calcium concentrations from 2.5 mEq/L to lower levels. There has been no rigorous systematic examination of the effects of such a reduction on clinical and biochemical outcomes.Retrospective cohort study.Medicare-eligible patients who received in-center hemodialysis at a large dialysis organization in January 2008 to December 2010.Facility conversion from predominant use (≥75% patients) of 2.50-mEq/L dialysate calcium to predominant use of lower dialysate calcium concentrations versus maintenance of predominant use of 2.50-mEq/L dialysate calcium.All-cause and cause-specific mortality and hospitalization, laboratory markers of metabolic bone disease, and drug utilization.Hierarchical mixed linear and Poisson models were fit to compare pre- to postconversion differences in outcomes between converter and matched control facilities. Results, expressed as relative rate ratios (RRRs) and delta-delta (change in mean values), were estimated for early (months 0-2) and late (months 3-12) postconversion to allow for possible latent effects.Facility conversion was associated with greater rates of hospitalization for heart failure exacerbation (late RRR, 1.27 [95% CI, 1.06-1.51]), hypocalcemia (early RRR, 1.19 [95% CI, 1.05-1.35]; late RRR, 1.39 [95% CI, 1.20-1.60]), and intradialytic hypotension (early RRR, 1.07 [95% CI, 1.02-1.11]; late RRR, 1.05 [95% CI, 1.01-1.10]), but no differences were observed for all-cause mortality or hospitalization rates. Facility conversion was also associated with comparative temporal decreases in serum calcium level, increases in serum phosphate and parathyroid hormone levels, and increases in use of phosphate binders, vitamin D, and calcimimetics.Possible residual confounding, generalizability beyond Medicare patients uncertain.There are potential safety concerns associated with the default use of dialysate calcium concentrations < 2.50 mEq/L, as well as biochemical evidence of poorer disease control despite associated greater medication use. Individualization of dialysate calcium concentration rather than predominant use of dialysate calcium concentrations < 2.50 mEq/L should be considered. |
| 2015 | Life-Threatening Hypercalcemia due to Graves' Disease and Concomitant Adrenal Failure: A Case Report and Review of the Literature. | Case Rep Endocrinol | A 47-year-old woman presented with the complaints of nausea, vomiting, and weight loss. She had a history of bilateral surrenalectomy due to Cushing's syndrome. On examination she had tachycardia and orthostatic hypotension. Laboratory examinations revealed hypercalcemia and suppressed parathyroid hormone levels. She also had thyrotoxicosis due to Graves' disease. The investigations to rule out a malignancy were negative. With steroid, zoledronic acid, and antithyroid drug treatment her symptoms were resolved and calcium level was normalized. This case highlights the importance of recognizing thyrotoxicosis and concomitant adrenal failure as a possible cause of severe hypercalcemia. |
| 2015 | Effects of lowering dialysate calcium concentration on mineral metabolism and hemodynamic parameters in hemodialysis patients. | Iran J Kidney Dis | It has been suggested that a dialysate calcium concentration of 1.5 mmol/L is a compromise between bone protection and cardiovascular risk. This study aimed to investigate the effect of reducing dialysate calcium concentration to 1.5 mmol/L on mineral metabolism and hemodynamic parameters.Dialysate calcium concentration was changed from 1.75 mmol/L to 1.5 mmol/L for 9 months and observed the effects on mineral metabolism and dialysis outcome parameters in 52 hemodialysis patients.The results at 9 months demonstrated that postdialytic serum calcium level decreased significantly from 109 ± 7 mg/L to 102 ± 6 mg/L, intact parathyroid hormone (PTH) increased from 372 ± 52 pg/mL to 606 ± 80 pg/mL, and the oral alfacalcidol increased from 1.4 ± 0.3 µg/w to 3.3 ± 0.4 µg/w. In patients with low PTH levels, continuous increase of PTH was observed. There were no significant variation in the oral calcium carbonate dose and serum levels of alkaline phosphatase, predialytic calcium, and pre- and postdialytic phosphorus. The ultrafiltration rate and postdialysis systolic blood pressure were significantly lower after reducing the dialysate calcium concentration to 1.5 mmol/L. Intradialytic hypotension and cramps were more frequent with this dialysate calcium concentration.These findings demonstrated that a decrease in dialysate calcium concentration from 1.75 mmol/L to 1.5 mmol/L improved mineral metabolism by prevention of postdialytic hypercalcemia and releasing oversuppression of PTH, but it was associated with more use of oral alfacalcidol and more hemodynamic impairment. |
| 2015 | Transient severe hypotension with once-weekly subcutaneous injection of teriparatide in osteoporotic patient: a case report and insight for the drug interaction between hypotensive agents and teriparatide. | J Med Invest | Teriparatide, a recombinant form of parathyroid hormone, were well recognized as a useful option for the treatment of the osteoporosis. Although some side effects of teriparatide include headache, nausea, dizziness, and limb pain were reported. Here we present a 80-year-old woman of transient asymptomatic hypotension with once-weekly subcutaneous injection of teriparatide for the treatment of osteoporosis with hypertension disease as acute-phase reactions. Systolic blood pressure decreased in both 30 min and 60 min after injection compared with before injection. Heart rate increased with passage of time. Statistically significant were observed among before, 30 min, 60 min after injection of teriparatide. Slight nausea was seen as subjective symptoms with the first and second injection after 30 min. This case indicates careful attention, at least 1 hr, was recommended with weekly subcutaneous injections of teriparatide in the treatment for osoteoproteic patient with hypertension decreases. This is a first report, to the best of our knowledge, to demonstrate the transient asymptomatic hypotension after once-weekly injection of teriparatide with hypertension disease. Transient hypotension occurred after injection of teriparatide during the treatment period and was asymptomatic except for the first 2 injections. |
| 2014 | Vitamin D deficiency is associated with orthostatic hypotension in oldest-old women. | J Intern Med | Orthostatic hypotension, a condition that mostly affects 'oldest-old' (i.e. ≥80 years) adults, is primarily explained by age-related dysfunction of blood pressure control. Vitamin D may contribute to blood pressure control. The aim of this study was to determine whether vitamin D deficiency is associated with orthostatic hypotension in oldest-old adults.Cross-sectional analysis at baseline of the EPIDOS study.Five French areas.A total of 329 community-dwelling oldest-old women (mean age 83.3 ± 0.2 years).Orthostatic hypotension was defined as a systolic blood pressure drop of ≥20 mmHg and/or a diastolic blood pressure drop of ≥10 mmHg within 3 min of standing. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25OHD) concentration ≤10 ng mL(-1) . Covariates included in the models were age, body mass index, diabetes mellitus, supine mean arterial pressure, number of drugs taken per day, use of antihypertensive or psychoactive drugs, cognition, quadriceps strength, current smoking, alcohol consumption, serum concentrations of parathyroid hormone, calcium and creatinine and season of testing.Diastolic orthostatic hypotension was observed more often among women with vitamin D deficiency (19.2%) compared to those without (10.0%; P = 0.03). There was an inverse linear association between 25OHD concentration and change in diastolic blood pressure after 3 min of standing (adjusted β = -0.07, P = 0.046). Similarly, 25OHD deficiency was associated with orthostatic hypotension [adjusted odds ratio (OR) 3.36, P = 0.004], specifically with diastolic orthostatic hypotension (adjusted OR 3.81, P = 0.003).25OHD deficiency was associated with orthostatic hypotension in oldest-old women, due to a greater drop in diastolic blood pressure on standing. This finding may lead to better understanding of the pathophysiology of falls in oldest-old adults with vitamin D deficiency. |
| Correlation of serum magnesium with cardiovascular risk factors in maintenance hemodialysis patients--a cross-sectional study. | Magnes Res | Changes in serum magnesium (Mg) may affect some clinical features of patients on maintenance hemodialysis (HD). The aims of our study were to evaluate the correlation between serum Mg concentration and clinical characteristics in Chinese HD patients, and to determine whether it has any relevance for cardiovascular outcomes.98 chronic HD patients were recruited, and clinical features related to cardiovascular disease (CVD) were measured: the correlation between Mg and these characteristics was analyzed.In patients who were hypomagnesemic, serum Mg, creatinine (Scr), albumin (Alb), pre-albumin (pre-Alb) levels, protein catabolic rate per normalized body weight (nPCR), dietary protein intake (DPI), triceps skin fold (TSF) thickness, mid-arm circumference (MAC), mean mid-arm circumference (MAMC), subjective global assessment (SGA) scores and Kt/V were lower than in hypermagnesemic patients. On the other hand, the incidence of intradialytic hypotension (IDH), levels of serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), C reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c) levels, carotid artery plaque (CAP), and carotid intima-media thickness (CIMT) (all p<0.05, respectively) were higher in patients with low serum magnesium. Correlation analysis showed Mg to be not only positively associated with the nutritional status index, but also negatively correlated with other characteristics, such as IDH incidence, Kt/V, Ca, P, iPTH, CRP, HDL-c, CAP, CIMT (p<0.05, respectively). There was no significant correlation between Mg and low-density lipoprotein cholesterol (LDL-c), lipoprotein-a (LP-a), cholesterol (TC), serum triglycerides (TG), or subjective global assessment (SGA) scores (p>0.05, respectively). Multiple linear regression analysis showed that Mg was negatively associated with CIMT, a direct predictor of CVD (β coefficient=-0.260, p=0.009).It is suggested that lower serum Mg reflects poorer nutritional status and that it is also associated with other risk factors for cardiovascular disease in hemodialysis patients, such as greater incidence of IDH, poorer HD adequacy, deteriorating calcium-phosphate metabolism, inflammation and CIMT. |
| 2013 | Efficacy and safety of lanthanum carbonate on chronic kidney disease-mineral and bone disorder in dialysis patients: a systematic review. | BMC Nephrol | Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication in CKD patients, particularly in those with end-stage renal disease that requires dialysis. Lanthanum carbonate (LC) is a potent, non-aluminum, non-calcium phosphate binder. This systematic review evaluates the efficacy and safety of LC in CKD-MBD treatment for maintenance-dialysis patients.A systematic review and meta-analysis on randomized controlled trials (RCTs) and quasi-RCTs was performed to assess the efficacy and safety of LC in maintenance hemodialysis or peritoneal dialysis patients. Analysis was performed using the statistical software Review Manager 5.1.Sixteen RCTs involving 3789 patients were identified and retained for this review. No statistical difference was found in all-cause mortality. The limited number of trials was insufficient to show the superiority of LC over other treatments in lowering vascular calcification or cardiovascular events and in improving bone morphology, bone metabolism, or bone turn-over parameters. LC decreased the serum phosphorus level and calcium × phosphate product (Ca × P) as compared to placebo. LC, calcium carbonate (CC), and sevelamer hydrochloride (SH) were comparable in terms of controlling the serum phosphorus, Ca × P product, and intact parathyroid hormone (iPTH) levels. However, LC resulted in a lower serum calcium level and a higher bone-specific alkaline phosphatase level compared with CC. LC had higher total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared with SH. LC-treated patients appeared to have a higher rate of vomiting and lower risk of hypercalcemia, diarrhea, intradialytic hypotension, cramps or myalgia, and abdominal pain. Meta-analysis showed no significant difference in the incidence of other side effects. Accumulation of LC in blood and bone was below toxic levels.LC has high efficacy in lowering serum phosphorus and iPTH levels without increasing the serum calcium. Current evidence does not show a higher rate of adverse effects for LC compared with other treatments, except for a higher incidence of vomiting. Moreover, LC accumulation in blood and bone was below toxic levels. Well-designed studies should be conducted to evaluate the long-term effects of LC. |
| 2013 | Low calcium dialysate combined with CaCO in hyperphosphatemia in hemodialysis patients. | Exp Ther Med | This aim of this study was to observe the effects of the application of low calcium dialysate (LCD) combined with oral administration of CaCO in the treatment of hyperphosphatemia, as well as blood Ca, calcium-phosphate product (CPP), parathyroid hormone (PTH) and blood pressure in patients undergoing hemodialysis. Thirty-one maintenance hemodialysis (MHD) patients with hyperphosphatemia, but normal blood Ca, underwent dialysis with an initial dialy-sate Ca concentration (DCa) of 1.50 mmol/l for six months and then with 1.25 mmol/l for six months. The patients who underwent dialysis with a DCa of 1.25 mmol/l were treated orally with 0.3 g CaCO tablets three times a day. In the third and sixth months [observation end point (OEP)] of the dialysis, the concentrations of Ca, phosphorus and intact PTH (iPTH) were measured; blood pressure and side-effects prior to and following dialysis were also observed. The Ca, CPP and iPTH levels increased (P<0.05) in the sixth month of treatment with a DCa of 1.50 mmol/l. However, the Ca concentration declined to a certain degree, CPPs decreased significantly (P<0.05) and the iPTH concentration increased following treatment with a DCa of 1.25 mmol/l for six months. The incidence rate of adverse effects of LCD was 12.9% (4/31); the effects were mainly muscle spasms, hypotension and elevated PTH. The periodic application of LCD combined with the oral administration of CaCO effectively reduced serum phosphorus and CPPs among MHD patients with hyperphosphatemia, indicating that the treatment may be used clinically. |
| 2013 | Dialysate calcium concentration and mineral metabolism in long and long-frequent hemodialysis: a systematic review and meta-analysis for a Canadian Society of Nephrology clinical practice guideline. | Am J Kidney Dis | Patients treated with conventional hemodialysis (HD) develop disorders of mineral metabolism that are associated with increased morbidity and mortality. More frequent and longer HD has been associated with improvement in hyperphosphatemia that may improve outcomes.Systematic review and meta-analysis to inform the clinical practice guideline on intensive dialysis for the Canadian Society of Nephrology.Adult patients receiving outpatient long (≥5.5 hours/session; 3-4 times per week) or long-frequent (≥5.5 hours/session, ≥5 sessions per week) HD.We included clinical trials, cohort studies, case series, case reports, and systematic reviews.Dialysate calcium concentration ≥1.5 mmol/L and/or phosphate additive.Fragility fracture, peripheral arterial and coronary artery disease, calcific uremic arteriolopathy, mortality, intradialytic hypotension, parathyroidectomy, extraosseous calcification, markers of mineral metabolism, diet liberalization, phosphate-binder use, and muscle mass.21 studies were identified: 2 randomized controlled trials, 2 reanalyses of data from the randomized controlled trials, and 17 observational studies. Dialysate calcium concentration ≥1.5 mmol/L for patients treated with long and long-frequent HD prevents an increase in parathyroid hormone levels and a decline in bone mineral density without causing harm. Both long and long-frequent HD were associated with a reduction in serum phosphate level of 0.42-0.45 mmol/L and a reduction in phosphate-binder use. There was no direct evidence to support the use of a dialysate phosphate additive.Almost all the available information is related to changes in laboratory values and surrogate outcomes.Dialysate calcium concentration ≥1.5 mmol/L for most patients treated with long and long-frequent dialysis prevents an increase in parathyroid hormone levels and decline in bone mineral density without increased risk of calcification. It seems prudent to add phosphate to the dialysate for patients with a low predialysis phosphate level or very low postdialysis phosphate level until more evidence becomes available. |
| 2012 | The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women. | Bone | Parathyroid hormone (PTH), currently the only marketed anabolic treatment for osteoporosis, is available as the full-length hormone, human PTH1-84, or as the human PTH1-34 fragment (teriparatide). Both must be administered as a daily subcutaneous (sc) injection. A new oral formulation of human PTH1-34 (PTH134) is being developed as a more convenient option for patients. In this single-center, partially-blinded, incomplete cross-over study, the safety, tolerability, and exposure of oral PTH134 (teriparatide combined with 2 different quantities of the absorption enhancer 5-CNAC) were assessed in 32 healthy postmenopausal women. 16 subjects were randomized to receive 4 single doses out of 6 different treatments: placebo, teriparatide 20 μg sc, or 1, 2.5, 5 or 10 mg of oral PTH134 formulated with 200 mg 5-CNAC. Subsequently, another 16 subjects were randomized to receive 4 out of 6 different treatments: placebo, teriparatide 20 μg sc, or 2.5 or 5 mg of oral PTH134 formulated with either 100 or 200 mg 5-CNAC. Doses were given ≥6 days apart. All doses of PTH134 were rapidly absorbed, and showed robust blood concentrations in a dose-dependent manner. Interestingly, PTH1-34 disappeared from blood faster after oral than after sc administration. Specifically, 2.5 and 5 mg PTH134 (containing 200 mg 5-CNAC) demonstrated Cmax and AUC0-last values closest to those of sc teriparatide 20 μg (Forsteo®). Mean+/-SD hPTH134 Cmax values were, respectively, 74+/-59, 138+/-101, 717+/-496, and 1624+/-1579 pg/mL for 1, 2.5, 5, and 10 mg doses of this peptide administered with 200 mg 5-CNAC; while mean+/-SD AUC (0-last) values were, respectively, 30+/-40, 62+/-69, 320+/-269, and 627+/-633 h*pg/mL. The corresponding estimates for teriparatide 20 μg sc were 149+/-35 for Cmax and 236+/-58 for AUC (0-last) Ionized calcium remained within normal limits in all treatment groups except for 3 isolated events. Nine subjects withdrew due to treatment-related AEs. Of those, seven were taking PTH134 2.5 or 5 mg: three withdrew for symptomatic hypotension (two of whom were in the 200 mg 5-CNAC group), three because of delayed vomiting (two from the 200 mg 5-CNAC group), one was proactively withdrawn by the investigator for symptomatic hypercalcemia (receiving 2.5 mg/100 mg 5-CNAC) at slightly supra-normal total calcium but normal ionized serum calcium levels. One subject receiving teriparatide and one receiving placebo withdrew for symptomatic hypotension. No serious AEs were reported. In conclusion, the study demonstrated potential therapeutically relevant PTH1-34 systemic exposure levels after oral administration of PTH1-34 formulated with the absorption enhancer 5-CNAC. Doses of 2.5 and 5 mg of oral PTH134 achieved exposure levels closest to those of teriparatide 20 μg sc, with a comparable incidence of AEs in healthy postmenopausal women. |
| 2012 | Predictors of quality of life of hemodialysis patients in India. | Indian J Nephrol | Little is known about the quality of life and survival in the patients on maintenance hemodialysis (HD) in India. Poor nutrition and dialysis noncompliance is common. This study investigates the factors that affect the quality of life (QoL) in HD patients in India. This cross-sectional study included 78 patients on HD for ≥ two months. Demographic, nutritional, functional subjective global assessment and Kidney Disease Quality of Life (KDQOL-36) assessments were done. Predictors of QoL were assessed by regression analysis. The mean calorie and protein intake were 1245 ± 116.9 kcal and 0.86 ± 0.19 g/kg/day respectively. Male gender (OR = 9.68), serum parathyroid hormone PTH <150 pg/ml (OR = 0.03), age ≤65 years (OR = 1.25), no catheter use (OR = 1.9) and hospitalizations (OR = 0.11), were independent predictors of total score ≥50. Independent predictors of physical component summary (PCS) >25 were male gender (OR = 5.06) and urine output at start of dialysis (OR = 1.05). Independent predictors of mental component summary (MCS) ≥25 were male gender (OR = 11.02), serum PTH > 150 pg/ml (OR = 0.15), daily protein intake of >0.8 g/kg and caloric intake >20 K.cal/kg (OR = 10.8). Patients with urine output >1 liter per day had more hypotensive episodes during dialysis (r = 0.56, P = 0.045), more headaches (r = 0.63, P = 0.006) but that did not affect the PCS significantly. Low PTH (<150 pg/ml) (OR = 1.29), multiple access failures (OR = 3.36) and total score ≤50 (OR = 0.09) were independently associated with increased hospitalization. Males, patients with serum PTH >150 pg/ml and those not on catheter had better total score. Though patients with higher urine output had better PCS, those with output >1 liter had higher incidence of hypotension and dialysis-related headache. Protein-energy malnutrition affected the MCS significantly. Dialysis noncompliance seen in one-fourth of the population did not affect the scores significantly. |
| [Lung carcinoma with paraneoplastic hyponatremia and hypercalcemia]. | Med Pregl | Among the numerous paraneoplastic syndromes of the lung carcinoma, metabolic manifestations are of the particular clinical relevance. They are the consequence the prominent neurosecretory activity of certain peptides and hormones, mostly within amine precursor uptake and decarboxylation (APUD) secretion. Small cell lung carcinoma is the most common cause of paraneoplastic syndromes. Ectopically produced proteins by the tumor are structurally similar but biologically less active than the "true" hormones, which may be clinically manifested by absent, less frequent or milder symptoms of the hormonal imbalance.Malignant hyponatremia may be caused by arginine-vasopressin imbalance within the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), or by hypersecretion of the atrial natriuretic peptide (ANP). Beside the postural hypotension, clinical picture is characterized by neurological symptoms caused by plasma hypo-osmolality, resulting in detection of the occult pulmonary neoplasm as well as post-therapeutic exacerbation of the small cell carcinoma.Malignant hypercalcemia is the most common paraneoplastic endocrine syndrome. In about 80% of the lung carcinomas without hone metastases it is caused by an increase of the parathyroid hormone-releasing protein (PTH-rP) in interaction with certain cytokines, products of the autochthonous neuroendocrine tumor secretion, predominantly in the squamous cell carcinoma. The cells expressing PTH-rP show coexpression of some neuroendocrine products.Different degrees of hypercalcemia cause heterogenous manifestations--from fatigue, anorexia, hone pains through polyuria, polydipsia, gastrointestinal complaints all the way to confusion, lethargy, coma and death. In addition to prevention of the intravascular volume overload, the treatment occasionally necessitates substitution of calcitonin possibly with plicamycin and gallium nitrate. |
| 2007 | Uraemic itching: do polymethylmethacrylate dialysis membranes play a role? | Nephrol Dial Transplant | Patients undergoing chronic renal replacement therapy by haemodialysis (HD) suffer from chronic itching, the prevalence of which is very high. Many of the available treatment options are ineffective, but, as it has been shown that Polymethylmethacrylate based dialysis membranes (PMMA) membranes remove a wide range of 'middle molecules' and improve such long-term complications of HD as carpal tunnel syndrome and malnutrition, they may also have an effect on uraemic itching.This prospective study enrolled eight patients undergoing standard HD with low-flux synthetic membranes and suffering from chronic itching. The strength and duration of itching was evaluated by the patients themselves at each study time-point using a visual analogue scale (VAS). After a baseline evaluation, the patients were switched to a PMMA membrane for 6 months during which their pre-dialysis haemoglobin, haematocrit, total protein, albumin, urea, creatinine, phosphate, intact parathyroid hormone (i-PTH), serum bile acid, beta2-microglobulin, C-reactive protein (CRP) levels, and eKt/V were measured, and any general complaints were recorded.The self-assessed VAS itching strength scores decreased by 15% after 1 month, 30% after 2 months, and 55% after 6 months, and itching duration decreased by, respectively, 10, 22 and 44% at the same time; 2 months after the end of the study, both scores had slightly increased. There were no statistically significant differences in the pre-dialysis blood chemistry values or eKt/V at the four study time-points, but beta2-microglobulin levels significantly decreased (P < 0.03); the decrease in CRP levels was not significant (P < 0.06). Furthermore, four patients showed a trend towards a lower incidence of intradialytic hypotension.These findings support the hypothesis that a PMMA dialyser may improve renal itching in ESRD patients. This effect is not mediated by increased dialysis efficiency or an improvement in other biochemical parameters, but we can speculate that ionic substances may be directly or indirectly adsorbed into the polymer composition of BG-U series (PMMA membrane dialyser). We are currently undergoing further studies using a proteomic approach. |
| 2007 | Improvement of bone and mineral parameters related to adynamic bone disease by diminishing dialysate calcium. | Bone | The existence of adynamic bone disease (ABD) as most prevalent form of renal osteodystrophy in recent years and its reduced ability to handle an exogenous calcium load has implied a higher risk for vascular and soft-tissue calcifications. The effect of low dialysate calcium (LCD) on parathyroid hormone (PTH) secretion in ABD patients has not yet sufficiently been clarified. This randomized, prospective study aimed to compare the effects of LCD and high calcium dialysate (HCD) on the evolution of bone and mineral parameters related to ABD in dialysis patients.52 out of 60 patients with predialysis intact PTH<100 pg/ml completed this study and were equally distributed over LCD (1.25 mmol/l) or HCD (1.75 mmol/l) treatment. The duration of the study was 6 months and the only peroral phosphate binder administered was calcium carbonate. Total and ionised calcium were measured monthly in serum before and after dialysis while serum parameters relevant to bone were measured at the enrollment and at 3-month intervals.There were no differences in predialysis mean phosphate or calcium x phosphorus product (Ca x P). The most common side effects of both treatments were comparable. Hypotension occurred in 16% and 17% and cramps in 6% and 8% of the dialysis sessions, in the HCD and LCD group, respectively. The groups did not differ in the mean tCa before dialysis, but this parameter was significantly higher in the HCD group vs. LCD at the end of dialysis (2.59+/-0.18 vs. 2.44+/-0.19 mmol/l; p<0.01). The patients of the HCD group also had a significantly higher mean iCa both before (1.08+/-0.05 vs. 1.04+/-0.06 mmol/l; p=0.02) and at the end of dialysis (1.18+/-0.04 vs. 1.48+/-0.04 mmol/l; p<0.01). There were no differences within the LCD group between baseline and end of dialysis treatment values of tCa and iCa. However, the mean tCa and iCa were markedly increased at the end of dialysis in the HDC group [2.40+/-0.21 vs. 2.59+/-0.18 mmol/l (p<0.01); 1.08+/-0.05 vs. 1.18+/-0.04 mmol/l (p<0.01)]. Mean serum levels of iPTH and total alkaline phosphatase in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels [(38.6+/-22.9 vs. 63.3+/-46.0 vs. 78.6+/-44.7 pg/ml); (59.5+/-18.7 vs. 75.9+/-26.7 vs. 84.0+/-35.4 U/l)], respectively, and bone alkaline phosphatase increased also only after 6 months of treatment (23.4+/-7.3 U/l vs. 35.6+/-22.3). The bone markers in the HCD group did not change. At the end of the study all bone parameters in the LCD group were significantly higher than in the HCD group.There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l, probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion. Hence, LCD might be considered a valuable therapeutic option for ABD patients. |
| 2006 | Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients. | Cochrane Database Syst Rev | Calcimimetic agents have recently been evaluated in the treatment of secondary hyperparathyroidism (SHPT) as add-on therapy to calcitriol and vitamin D analogues and dietary phosphate binders.To evaluate the benefits and harms of calcimimetics for the prevention of secondary hyperparathyroid bone disease (including osteitis fibrosa cystica and adynamic bone disease) in dialysis patients with chronic kidney disease (CKD).MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and conference proceedings were searched for randomised controlled trials (RCTs) evaluating any calcimimetic against placebo or another agent in pre-dialysis or dialysis patients with CKD.We included all RCTs of any calcimimetic agent, cinacalcet HCl (AMG-073, Sensipar), NPS R-467 or NPS R-568 administered to patients with CKD for the treatment of SHPT.Data were extracted on all relevant patient-centred and surrogate outcomes. Analysis was by a random effects model and results expressed as relative risk (RR) or weighted mean difference (MD) with 95% confidence intervals.Eight studies (1429 patients) were identified, which compared a calcimimetic agent plus standard therapy to placebo plus standard therapy. The end of treatment values of parathyroid hormone (pg/mL) (MD -290.79, 95% CI -360.23 to -221.34), serum calcium (mg/dL) (MD -0.85, 95% CI -1.14 to -0.56), serum phosphorus (mg/dL) (MD -0.29, 95% CI -0.50 to -0.08) and the calcium by phosphorus product (mg(2)/dL(2))(MD -7.90, 95% CI -10.25 to -5.54) were significantly lower with calcimimetics compared to placebo. No significant effects on patient-based endpoints were demonstrated except for the risk of hypotension which was significantly reduced with calcimimetics compared to placebo (RR 0.53, 95%CI 0.36 to 0.79).Calcimimetic treatment of SHPT leads to significant improvements in biochemical parameters that observational studies have shown to be associated with increased mortality, cardiovascular risk and osteitis fibrosa, but patient-based benefits have not yet been demonstrated in trials. For patients with SHPT, the benefits of calcimimetics over standard therapy remain uncertain until further RCTs become available. |
| 2006 | Intradialytic changes of serum magnesium and their relation to hypotensive episodes in hemodialysis patients on different dialysates. | Hemodial Int | Magnesium is a crucial mineral, involved in many important physiological processes. Magnesium plays a role of maintaining myocardial electrical stability in hemodialysis patients. Intradialytic hypotension is a common complication of dialysis and it is more common with acetate dialysate. The significance of the intradialytic changes of magnesium and their relation to parathyroid hormone (PTH) level and calcium changes during dialysis, and their relation to hypotensive episodes during dialysis are interesting. The aim of this work is to investigate the intradialytic changes of serum magnesium in chronic hemodialysis patients with different hemodialysis modalities and the relation to other electrolytes and to PTH, and also the relation to intradialytic hypotension. The present study was conducted on 20 chronic renal failure patients. All patients were on regular hemodialysis thrice weekly 4 hr each using acetate dialysate (group I). To study the effect of an acetate-based dialysate vs. a bicarbonate-based dialysate on acute changes of magnesium, calcium, phosphorus, and PTH during a hemodialysis session, the same patients were shifted to bicarbonate dialysis (group II). All patients were subjected to full history and clinical examination, predialysis laboratory assessment of blood urea nitrogen (BUN), serum creatinine, albumin, and hemoglobin, serial assessment of magnesium, calcium, phosphorus, and parathyroid hormone at the start of the hemodialysis session, 2 hr later, and at the end of the session, blood pH, and electrocardiogram (ECG) presession and postsession. All patients were urged to fix their dry weight, diet, and current medications. None of the patients had diabetes, neoplasia, liver disease, or cachexia, nor had they been recently on magnesium-containing drugs or previously parathyroidectomized. Hemodialysis sessions were performed by volumetric dialysis machines using the same electrolyte composition. Magnesium level significantly increased in the bicarbonate group at the end of dialysis (0 hr: 2.73+/-0.87, 2 hr: 3.21+/-1.1, and at 4 hr: 5.73+/-1.45 mg/dL, p value <0.01), while it significantly decreased in the acetate group (0 hr: 3.00+/-0.58, 2 hr: 2.26+/-0.39, 4 hr: 1.97+/-0.33 mg/dL, p value <0.01). Calcium level significantly increased in the bicarbonate group (p=0.024) but not in the acetate group. Phosphorus level significantly decreased in both acetate and bicarbonate groups. PTH level did not significantly change in either group, p value > or =0.05. Blood pH significantly increased, changing from acidic to alkaline pH, with both modalities of hemodialysis. ECG showed no significant changes during sessions with either type of dialysate. Hypotension was significantly higher in group I compared with group II (p=0.01), and this hypotension was positively correlated with a decrease in serum magnesium level in group I. Intradialytic changes in serum magnesium have no correlation with intradialytic changes in serum calcium or with PTH level. However, it was significantly correlated with hypotension during the dialysis session, especially with acetate dialysate. Further investigations are needed to determine whether or not this is true in patients using bicarbonate dialysis. |
| 2006 | Review of dialysate calcium concentration in hemodialysis. | Hemodial Int | The dialysate calcium (Ca) concentration for hemodialysis (HD) patients can be adjusted to manage more optimally the body's Ca and phosphate balance, and thus improve bone metabolism as well as reduce accelerated arteriosclerosis and cardiovascular mortality. The appropriate dialysate Ca concentration allowing this balance should be prescribed to each individual patient depending on a multitude of variable factors relating to Ca load. A lower dialysate Ca concentration of 1.25 to 1.3 mmol/L will permit the use of vitamin D supplements and Ca-based phosphate binders in clinical practice, with much less risk of Ca loading and resultant hypercalcemia and calcification. Low Ca baths are useful in the setting of adynamic bone disease where an increase in bone turnover is required. However, low Ca levels in the dialysate may also predispose to cardiac arrhythmias and hemodynamically unstable dialysis sessions with intradialytic hypotension. Higher Ca dialysate is useful to sustain normal serum Ca levels where patients are not taking Ca-based binders or if Ca supplements are not able to normalize serum levels. Suppression of hyperparathyroidism is also effective with dialysate Ca of 1.75 mmol/L, but hypercalcemia, metastatic calcification, and oversuppression of parathyroid hormone are risks. Dialysate Ca of 1.5 mmol/L may be a compromise between bone protection and reduction in cardiovascular risk for conventional HD and is a common concentration used throughout the world. The increase in longer, more frequent dialysis such as short-daily and nocturnal HD, however, provides another challenge with regard to optimal dialysate Ca levels and higher levels of 1.75 mmol/L are probably indicated in this setting. Difficulties in determining the ideal dialysate Ca occur because of the complex pathophysiology of bone and mineral metabolism in HD patients and there needs to be a balance between dialysis prescription and other treatment modalities. To optimize management of the abnormal Ca balance, other aspects of this disorder need to be more fully clarified and, with evolving medications for phosphate control and treatment of secondary hyperparathyroidism, as well as the emergence of a multitude of different HD regimes, further studies are required to make definitive recommendations. At present, we need to maintain flexibility with HD treatments and so dialysate Ca needs to be individualized to meet the specific requirements of patients by optimizing management of renal bone disease and simultaneously reducing metastatic calcification and cardiovascular disease. |
| 2005 | [Transient hyponatremia the first symptome of multiple endocrine neoplasia type 1 (MEN 1)--case report]. | Pol Arch Med Wewn | Transient character of laboratory abnormalities is usually explained as a false result of estimation. Spontaneous disappearance of laboratory abnormalities could be recognized as non-important and contradicting serious disease. Presented case of multiple endocrine neoplasia type 1 (MEN 1) denies these assumptions. Sixty-nine-years old woma was admitted to the internal department because of weakness, fever, dehydration and hypotension--symptom accompanying an upper respiratory infection. Moderate hyponatremia (122.6 mmol/l) was found in a routine laborator examination. All clinical symptoms as well as hyponatremia disappeared during hospitalization. Transient hyponatremi was not ignored. Further laboratory and hormonal investigations were performed. Fasting, morning serum cortisol concentration and 24-hours urinary excretion of free corticosterids were decreased and Synacten stimulation test reveale incomplete cortisol stimulation. Pituitary tumour was found in the CT scan. Moreover blood ionized calcium an parathyroid hormone were elevated. These results revealed secondary adrenal insufficiency, non-functioning pituitary tumor and hyperparathyroidism. Removal of pituitary adenoma was done. Asymptomatic hypercalcemia persists. Presented MEN 1 was atypical because: 1. Usually hyperparathyroidism is the first and most frequent symptom while in our patient the first symptom was transient hyponatremia secondary to the pituitary tumor, 2. was diagnosed in the old age while the majority of MEN 1 patients are younger, 3. asymptomatic course of hypercalcemia indicates that in some of elder patients removal of the parathyroid glands might not be necessary. |
| 2004 | Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns. | Am J Physiol Regul Integr Comp Physiol | Renal parathyroid hormone (PTH) action is often studied at high doses (100 microg PTH/kg) that lower mean arterial pressure significantly, albeit transiently, complicating interpretation of studies. Little is known about the effect of acute hypotension on proximal tubule Na(+) transporters. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 +/- 3 to 78 +/- 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (<2 min) decreased arterial blood pressure to 51 +/- 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low-density membranes enriched in apical markers. PTH at much lower doses (<1.4 microg.kg(-1).h(-1)) did not change blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na(+) reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking of transporters to the surface is not the likely mechanism; in comparison, hypotension secondary to high-dose PTH blocks the primary diuretic effect of PTH but does not inhibit the PTH-stimulated redistribution of NHE3 and NaPi2 to the base of the microvilli. |
| 2003 | Isolated adrenocorticotropic hormone deficiency presenting with hypercalcemia in a patient on long-term hemodialysis. | Am J Kidney Dis | The authors report on a 44-year-old female hemodialysis (HD) patient who presented with hypercalcemia secondary to isolated adrenocorticotropic hormone (ACTH) deficiency. She had been suffering from nausea and abdominal pain caused by recurrent esophageal ulcer. Blood calcium (Ca) adjusted for serum albumin concentration was increased to 14.9 mg/dL (3.72 mmol/L) concurrently with fever and hypotension. Serum intact parathyroid hormone (PTH)-related peptide was not elevated, but serum intact PTH and 1,25-(OH)2 vitamin D3 were decreased to 31 pg/mL (ng/L) and 8.1 pg/mL (2.6 pmol/L), respectively. Endocrinologic examination found that plasma ACTH was reduced below 5.0 pg/mL (0.22 pmol/L). A single ACTH stimulation normally increased blood cortisol, whereas a single corticotropin-releasing hormone injection failed to increase plasma ACTH and cortisol. Pituitary magnetic resonance imaging disclosed no enlargement of pituitary gland. Circulating bone formation and absorption markers were not elevated. Blood Ca was normalized shortly after pamidronate disodium administration without glucocorticoid supplementation. This case suggested that secondary adrenal insufficiency caused by isolated ACTH deficiency could be an occult cause of severe hypercalcemia in HD subjects. |
| 1999 | [Relationship between hypotension during hemodialysis and autonomic dysfunction in diabetic hemodialysis patients]. | Hunan Yi Ke Da Xue Xue Bao | To observe the change of autonomic nerve function in diabetes mellitus(DM) patients who receive hemodialysis and to explore the relationship between this change and hypotension during hemodialysis.Twenty-five DM patients and 40 chronic glomerulonephritis(CGN) patients who received hemodialysis were checked. We tested their coefficient of variation R-R(CVR-R) in ECG, difference of systolic blood pressure between lying and standing positions, and serum parathyroid hormone(PTH); monitored the decrease of blood pressure during hemodialysis.The rate(80.0%) of autonomic dysfunction(AD) in DM group is significantly higher than that(57.5%, P < 0.05) in CGN group. The rate(37.2%) of hypotension in those who had AD was significantly higher than that(18.2%, P < 0.05) in those who had normal autonomic nerve function during hemodialysis. No significant difference was found in PTH between each group.DM patients who receive hemodialysis are often complicated with AD, which is one of the reasons that causes hypotension during hemodialysis. |
| 2001 | Phase I trial of a twice-daily regimen of amifostine with ifosfamide, carboplatin, and etoposide chemotherapy in children with refractory carcinoma. | Cancer | Amifostine protects normal tissues against chemotherapy and radiation-induced toxicity without loss of antitumor effects. Evidence suggests that multiple daily doses of amifostine may improve its cytoprotective effects. The purpose of this study was to assess the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of twice-daily doses of amifostine with ifosfamide, carboplatin, and etoposide (ICE) chemotherapy for children with refractory malignancies and to determine the pharmacokinetic properties of amifostine, WR-1065, and the disulfide metabolites of amifostine.Patients with refractory malignancies were treated with amifostine 15 minutes before and 2 hours after chemotherapy with ifosfamide (3 g/m(2) per dose on Days 1 and 2) and carboplatin (635 mg/m(2) on Day 3). Etoposide was administered on Days 1 and 2 (150 mg/m(2)). The starting dose of amifostine was 740 mg/m(2). Pharmacokinetic studies were performed after the first dose of amifostine.Twelve patients received 23 courses of ICE and amifostine. Dose-limiting toxicities for amifostine at 740 mg/m(2) were somnolence and anxiety. The other Grade 3 and 4 toxicities included asymptomatic, reversible hypocalcemia, vomiting, and reversible hypotension. At a dose of 600 mg/m(2), amifostine was well tolerated. Hypocalcemia, due to rapid, transient suppression of parathyroid hormone production, required close monitoring and aggressive intravenous calcium supplementation. Pharmacokinetic studies revealed high interpatient variability with rapid plasma clearance of amifostine and WR-1065. The median elimination half-life of amifostine (9.3 minutes) and WR-1065 (15 minutes) was much shorter than the disulfide metabolites (74.4 minutes).The recommended pediatric dose of amifostine for a twice-daily regimen is 600 mg/m(2) per dose (1200 mg/m(2)/day) with DLTs of anxiety and somnolence, lower than the previously recommended single dose of 1650 mg/m(2). |
| 2000 | Clinical relevance of cytokine production in hemodialysis. | Kidney Int Suppl | Blood-dialyzer interaction in hemodialysis has the potential to activate mononuclear cells leading to the production of inflammatory cytokines. The extent of activation is dependent on the dialyzer material used and is considered an index of biocompatibility. Cytokines, such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6, may induce an inflammatory state and are believed to play a significant role in dialysis-related morbidity. The interleukin hypothesis suggests that the release of proinflammatory cytokines acts as an underlying pathophysiologic event in hemodialysis-related acute manifestations, such as fever and hypotension. Nevertheless, a cytokine overproduction may alter sleep pattern in chronic hemodialyzed patients, thus explaining the presence of sleep disorders in these patients. A potential role of cytokines in chronic-related morbidity has also been suggested. High levels of some inflammatory cytokines are often associated with anemia caused by hyporesponsiveness to erythropoietin. Cytokine production may also play a relevant role in bone remodeling by regulating osteoblast/osteoclast cell functions and parathyroid hormone (PTH). Finally, cytokine release may have a long-term deleterious effect on mortality of uremic patients by altering immune response and increasing susceptibility to infections. Bioincompatibility of dialytic membranes may also contribute to malnutrition in dialysis patients by increasing the monocyte release of catabolic cytokines such as TNF-alpha and IL-6. Bioincompatible dialytic treatment may induce an inappropriate monocyte activation and cytokine production, which, in turn, may mediate some of the immune and metabolic dysfunction associated with hemodialysis. The use of biocompatible dialytic membranes appears to reduce the monocyte activation and to improve the survival of hemodialysis patients. |
| 1998 | The effect on blood pressure of an acute fall in ionized calcium during hemodialysis. A randomized study in two patients. | Clin Nephrol | Elevating serum ionized calcium levels is known to stabilize blood pressure during and after a hemodialysis session. The data on lowering calcium levels is limited.This study examined the responses to an acute drop in ionized calcium during a four hour hemodialysis session in two subjects who differed in the presence (patient 1) or absence (patient 2) of anti-hypertensive medication and average weight loss of 4 kg (patient 1) or 2 kgs (patient 2) with each dialysis. Parathyroid hormone (PTH) levels were normal (patient 1) or very high (patient 2). A calcium free dialysate was used and the calcium infusion rate distal to the dialyzer was varied to produce either no change in ionized calcium for 10 dialyses, or a fall of at least 0.2 mmol/l for 10 dialyses. The sequence was randomized and was blinded to the observers and patients.The fall in ionized calcium was similar in each individual, 0.37 +/- 0.11 and 0.34 +/- 0.05 mmol/l. PTH rose from 8.6 +/- 1.6 to 24.2 +/- 6.6 pmol/l for patient 1 and 144.6 +/- 59.9 to 234.8 +/- 32.3 pmol/l for patient 2: patient 1 showed a fall in blood pressure after dialysis associated with the fall in calcium. This was most pronounced in the upright position whereas there was no change for Patient 2. For Patient 1 standing mean blood pressure post-dialysis was 104 +/- 6 mmHg when the calcium was stable and 94 +/- 10 mmHg with hypocalcemia p <0.01. Mean blood pressure during dialysis was also lower with hypocalcemia 100 +/- 7 versus 92 +/- 9 p <0.05. There were no significant changes in blood pressure for patient 2. Neither of the patients had any symptoms attributable to hypotension or hypocalcemia.It was concluded that modest falls in ionized calcium were associated with a drop in standing blood pressure only when combined with other factors predisposing to vascular instability. Even so these decreases were small enough to be asymptomatic. |
| 1997 | Hemofiltration or hemodiafiltration with on-line production of substitution fluid: clinical observation of safety and effectiveness. | Chin Med J (Engl) | To observe the safety and cardiovascular stability of on-line hemofiltration (HF) or hemodiafiltration (HDF) and evaluate the clinical effectiveness of one HF or HDF session in addition to two hemodialysis (HD) sessions weekly.Forty patients were randomly divided into four groups: group predilutional (PRD) HF (filtration rate: 259-333 ml/min) group predilutional HDF (filtration rate: 167 ml/min) group postdilutional (POD) HDF (filtration rate: 83 ml/min) and group bicarbonate HD. The reduction rate of parathyroid hormone (PTH), beta 2-microglobulin (beta 2MG), alpha 1-microglobulin (alpha 1MG) and KT/V in the initial treatment of every month was observed, and the incidence of hypotension and pyretic reaction during each treatment was evaluated.After 4-month observation, the KT/V for Group POD HDF is better than that for the other three groups, and for Group PRD HDF is better than that for Group HF and HD. Serum level of PTH and beta 2MG was not decreased after every treatment in Group HD, and so was serum level of alpha 1MG in all groups. Significant removal of PTH and beta 2MG was observed in Group HF, PRD HDF and POD HDF. The monthly serum level of beta 2MG and KT/V were stable in all groups, but the monthly serum level of PTH tended to be decreased in Group HF, PRD, HDF, and POD HDF. The incidence of pyretic reaction in HF or HDF was the same as in HD. Although the ultrafiltration volume was significantly higher during HF or PRD HDF than during HD, the incidence of hypotension in HF or PRD HDF was similar to that in HD.On-line HF or HDF proved to be a safe and reliable method. POD HDF mode seems to have the best KT/V, HF or PRD HDF offers a better choice for preventing intradialytic hypotension. One HF or HDF session in addition to two HD sessions weekly is similarly effective to decrease the serum level of PTH and the proof of the clinical effectiveness of such a therapy awaits a long-term observation. |
| Increased nitric oxide production in hypotensive hemodialysis patients. | ASAIO J | A subset of patients on long-term hemodialysis have sustained hypotension, defined as a predialysis systolic pressure of < 100 mmHg. To determine the role of nitric oxide (NO), an important vasodilator, in this condition, the authors measured the plasma levels of nitrite (NO2-) and nitrate (NO3-), the known NO metabolites taken as an index of NO production, in 10 hypotensive patients on long-term hemodialysis. None of them had diabetes, cirrhosis of the liver, congestive heart failure, or infection. Fifteen age and gender-matched normotensive patients on hemodialysis were selected as control subjects. Measurements of plasma levels of nitrite and nitrate based on the Greiss reaction were made. There was no significant difference in hematocrit, serum intact parathyroid hormone, total calcium, inorganic phosphorus, albumin, heart rate, cardiac index, or interdialysis weight gain between these two groups. Plasma nitrite and nitrate levels did not correlate with either predialysis serum creatinine or blood urea nitrogen. The mean arterial pressure (MAP) was significantly lower and plasma nitrite and nitrate levels were significantly higher in chronic hypotensive patients than in normotensive patients (MAP: 68.30 +/- 3.24 mmHg vs 95.20 +/- 2.44 mmHg, p < 0.001; plasma nitrite and nitrate: 72.49 +/- 14.41 mumol/L vs 36.42 +/- 5.45 mumol/L, p < 0.05). In addition, MAP from hypotensive and normotensive patients on hemodialysis was inversely correlated with plasma levels of nitrite and nitrate (r = -0.54, p < 0.01). It was concluded that enhanced NO production in this subset of patients on hemodialysis may contribute to their chronic hypotension. |
| 1996 | A prospective comparison of bicarbonate dialysis, hemodiafiltration, and acetate-free biofiltration in the elderly. | Am J Kidney Dis | Hemodiafiltration (HDF) and more recently acetate-free biofiltration (AFB) have shown good blood purification and cardiovascular stability in young and middle-aged hemodialysis patients. It is not clear if this is also valid for elderly patients. Twelve patients aged more than 70 years (mean age +/- SD, 76 +/- 4 years) on regular dialysis for at least 5 months were treated with bicarbonate dialysis (BD), HDF, or AFB in a randomized sequence and prospectively followed for 6 months (72 dialysis sessions/patient) for each procedure. The dialysis solution (containing bicarbonate), blood flow rate, and dialysate flow rate were the same with all the methods. During HDF and AFB solutions containing bicarbonate at a concentration of 27 to 30 mEq/L and 145 mEq/L, respectively, were infused postdilution at a rate of 66 +/- 7 mL/min and 2.81 +/- 0.12 L/hr, respectively. During the period of observation we evaluated the number of intradialytic hypotensions, the episodes of nausea, vomiting, headache (dialysis intolerance), body weight, the interdialysis weight gain, the duration of the dialysis session, the number of hospitalizations/patient, and the length of hospitalization/patient. At the end of each observation period we determined: Kt/V, protein catabolic rate, acid base balance, serum creatinine, serum calcium, serum phosphorus, alkaline phosphatases, and serum intact parathyroid hormone. After the switch from BD to either HDF or AFB, the results have shown a significant reduction of dialysis hypotension episodes (18 percent on BD, 14 percent on HDF, and 13 percent on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.0001; and HDF v AFB, P = NS) and of dialysis intolerance (3.3 percent on BD, 1.3 percent on HDF, and 1.1 percent on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.019; and HDF v AFB, P = NS). Kt/V improved significantly after the switch from BD to either HDF or AFB (1.17 +/- 0.06 on BD, 1.32 +/- 0.12 on HDF, and 1.32 +/- 0.13 on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.003; HDF v AFB, P = NS). Protein catabolic rate also improved in HDF and AFB compared with BD (0.90 +/- 0.12 on BD, 1.03 +/- 0.15 on HDF, and 1.04 +/- 0.14 on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.009; and HDF v AFB, P = NS). AFB showed a better correction of acidosis compared either with BD or HDF (serum bicarbonate, 20.3 +/- 1.1 mEq/L on BD, 20.8 +/- 2.2 mEqL on HDF, and 22.2 +/- 2.4 mEq/L on AFB; BD v HDF, P = NS; BD v AFB, P = 0.01; and HDF v AFB, P = 0.030). The other parameters observed did not differ. In conclusion HDF and AFB show a better dialysis efficiency and a better hemodynamic tolerance compared with BD. This fact is associated with an improvement in protein intake as assessed by kinetic criteria. Acetate-free biofiltration has the further advantage of a better control of the acid-base balance compared with BD and HDF. HDF and AFB are useful dialytic options to traditional BD hemodialysis even in patients older than 70 years. |
| 1996 | Role of secondary hyperparathyroidism in the development of post-transplant acute tubular necrosis. | Nephron | Post-transplant cure tubular necrosis (ATN) represents the most frequent cause of delayed graft function in the immediate post-transplant period. Several causes have been associated with the development of post-transplant ATN such as donor and recipient ages, cold-warm ischemia times, HLA mismatches, and postoperative hypotension. In the present study, we retrospectively evaluated the role of secondary hyperparathyroidism and high parathyroid hormone (PTHi) blood levels in the development of post-transplant ATN. One hundred patients submitted to cadaveric renal transplant between January 1992 and March 1993 in our unit were included. Twenty-seven patients (27%) developed post-transplant ATN and seventy-three (73%) did not. Post-transplant ATN was significantly associated with gender (p < 0.01), recipient age (p < 0.01), number of transplantations (p < 0.01), time on hemodialysis (p < 0.001), cold ischemic time (p < 0.05) and PTHi levels (p < 0.001). The bivariate and multivariate statistical analyses demonstrated that the development of post-transplant ATN was significantly more frequent in females; retransplanted patients, patients with a time on dialysis of more than 5 years, recipients over 60 years old, patients with a PTHi blood level higher than 240 pg/ml (4 times normal level) and a cold ischemia time of more than 18 h. Based on these results, we conclude that high PTHi blood levels in the renal transplant recipients represent a relevant factor in the development of post-transplant ATN. The administration of intravenous pulsed of 1,25(OH)2D3 and/or a calcium channel blocker in the perioperative period could be useful to decrease the incidence and severity of post-transplant ATN in these patients. |
| 1995 | Endogenous nitric oxide is not involved in acute parathyroid hormone-induced hypotension in rat: effect of hypertension and hypoparathyroid status. | Horm Metab Res | The present study investigated the acute hypotensive effect of parathyroid hormone (PTH) in anesthetized adult spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats. Furthermore, in order to determine the possible contribution of nitric oxide (NO), a mediator of endothelium-dependent vasorelaxation, hypotensive responses to PTH were obtained in the presence of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis. The hypotensive effect of PTH (expressed as % of baseline blood pressure) was similar for the two strains. In the presence of L-NAME (18.5 mumol/kg), both strains demonstrated a similar hypotensive response to PTH, indicating that the hypotensive response to PTH is NO-independent. |
| 1993 | [Calcium blood changes in septic conditions. A review]. | Ugeskr Laeger | Hypocalcemia has been reported in critically ill patients over the last 10-15 years, however, measurements of Ca2+ in blood have not yet became routine in the treatment of severely ill patients. In order to stress the importance of calcium in such patients, a review of calcium changes in septic conditions is presented. In vitro studies show that the intracellular calcium metabolism is disturbed in these patients, and that the changes in extracellular calcium are probably secondary to the intracellular changes. Parathyroid hormone secretion is inappropriate in septic patients. The reason for this is unknown. Administration of calcium parenterally does not seem to affect the prognosis, however calcium seems to be beneficial in patients with hypotension. Since the level of Ca2+ in blood may have prognostic significance in septic patients, measurements of Ca2+ in blood should be used routinely in these patients, in order to point out "risk" patients as early as possible. |
| 1993 | Acute pancreatitis: a multisystem disease. | Gastroenterologist | Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP. |
| 1993 | Response of vasoactive substances to reduction of blood volume during hemodialysis in hypotensive patients. | Clin Nephrol | Hypotension is a frequent complication in patients subjected to regular hemodialysis. Insufficient regulation of blood pressure following dialysis with ultrafiltration has been attributed to a lack in hormone activation. To determine whether altered production of vasoactive hormones is involved in the breakdown of blood pressure regulation during hemodialysis (HD), blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), intact immunoreactive parathyroid hormone (iPTH) and arginine vasopressin (AVP) were examined. The relative BV was measured by continuous hemoglobinometry during the HD period of about 240 min. The total decrease in BV at the end of treatment was 23.5 +/- 4.8% of the pretreatment value. Systolic blood pressure (SBP) was 99.6 +/- 23.0 mmHg before dialysis compared with 74.6 +/- 18.8 mmHg at the end of dialysis and heart rate (HR) increased from 76.3 +/- 5.5/min before to 92.0 +/- 10.0/min at the end of dialysis. Despite the wide range of interindividual variance, the hormonal changes indicate that hypotensive patients under HD develop reduced sensitivity of the angiotensin-renin, adrenergic and AVP systems to volumetric stimuli. A paradoxical activation in iPTH and PRA independent Aldo secretions is apparent. |
| 1990 | Clinical experience with desferrioxamine in dialysis patients with aluminium toxicity. | Q J Med | A desferrioxamine (DFO) infusion test, using a DFO dose of 36.9 +/- 11.2 mg/kg (mean +/- SD), was performed in 50 consecutive dialysis patients undergoing diagnostic bone biopsy. In 30 patients whose bones stained positively for aluminium the serum aluminium level increased by an average of 373 +/- 250.4 ng/ml. The increase in 20 aluminium-negative patients was 231 +/- 179.2 ng/ml (p less than 0.05). Aluminium-positive patients had lower levels of immunoreactive parathyroid hormone (336 +/- 442 muleq/ml) than aluminium-negative patients (1278 +/- 1400 muleq/ml; p less than 0.05). A change in serum aluminium level of greater than 200 ng/ml after the administration of DFO was 73 percent sensitive and 50 percent specific, and had a positive predictive value of 69 percent for detecting positive bone aluminium staining. The combination of a baseline immunoreactive parathyroid hormone level less than 200 muleq/ml and a change in serum aluminium of greater than 200 ng/ml after DFO was 90 percent specific and had a positive predictive value of 85 percent. In the second phase of our study, 28 dialysis patients with aluminium toxicity received long-term therapy (11.0 +/- 4.3 months) with DFO at an average starting dose of 41.7 +/- 17.1 mg/kg, administered once weekly. The four deaths which occurred during this treatment involved the only patients who had advanced dialysis dementia. Seven patients with less severe neurological symptoms responded favourably. Fractures decreased from 1.7 fractures/patient/year to 0.1 fracture/patient/year. Muscular strength and overall functional class were improved or stable in 25 patients; myalgias and arthralgias were also stable or improved in 19 patients. After 5-7 months of treatment, serum aluminium levels decreased from 401 +/- 262 ng/ml to 245 +/- 217 ng/ml (p less than 0.01); erythrocyte mean corpuscular volume increased from 86.3 +/- 10.91 fl to 94.1 +/- 9.23 fl (p less than 0.02); and serum calcium decreased from 10.4 +/- 0.94 mg/dl to 9.9 +/- 0.70 mg/dl (p less than 0.02). Serum immunoreactive parathyroid hormone levels remained stable in 25 patients, but severe hyperparathyroidism developed rapidly in three patients. Eight patients with transfusional iron overload had no change in serum ferritin levels. Iron depletion developed in six patients, with a decrease in serum ferritin from 251 +/- 229.8 micrograms/l to 45 +/- 29.3 micrograms/l, and they required parenteral iron supplementation. Significant side-effects occurring during long-term DFO administration were hypotension (11 patients), gastrointestinal upset (seven patients), porphyria cutaneous tarda-like lesions (three patients), and transient visual disturbance (one patient). There was a decrease in stainable bone aluminium in all nine patients with paired bone biopsy specimens (pre- and post-DFO).(ABSTRACT TRUNCATED AT 400 WORDS) |
| 1989 | Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor. | Endocrinology | Patients with humoral hypercalcemia of malignancy display markedly increased serum calcium levels, reduced blood pressure, and tachycardia. The causative agent, humoral hypercalcemia of malignancy factor [also called PTH-related protein (PTHrp)] has been shown to interact with PTH receptors in bone and kidney. We compared human PTHrp-(1-34) with rat PTH-(1-34) for the effects of each peptide on cardiovascular function in unrestrained conscious rats. Both PTHrp and PTH decreased blood pressure in a dose-dependent manner over the concentration range of 0.3-30 micrograms/kg. PTHrp was approximately 3-fold more potent than PTH, producing up to a 50 mm Hg decrease in pressure within 2 min at 10 micrograms/kg. Both peptides increased heart rate more than 70 beats/min at this dose. However, PTH appeared to exert greater efficacy and potency than PTHrp in increasing heart rate in vivo. In the isolated and perfused rat heart, PTHrp and PTH produced positive chronotropic and positive inotropic effects as well as increased coronary flow. PTHrp was more potent and more effective than PTH. The time courses of these effects in the perfused heart preparations indicated that both peptides produced maximal effects within 1 min, with all responses returning to baseline within 10 min. In isolated helical strips of rat aorta, PTHrp and PTH relaxed norepinephrine-contracted tissues in a concentration-dependent fashion. A functional endothelium was not required for the relaxing effects of either peptide. These studies indicate that PTHrp and PTH decrease blood pressure by relaxing vascular tissue in an endothelium-independent manner. Also, these peptides directly increased heart rate, contractility, and coronary flow. Since PTHrp has recently been found in normal human cells, these studies suggest the possibility of PTHrp as a regulator or modulator of cardiovascular function. |
| 1989 | [Comparison of hypotensive effects of acutely administered human parathyroid hormone (1-34) in normal young and elderly subjects]. | Nihon Ronen Igakkai Zasshi | The effects of acute administration of human parathyroid hormone (1-34) [PTH(1-34)] on the blood pressure of 15 young (mean age +/- SD, 20.9 +/- 1.7 years; 7 males and 8 females) and 11 elderly (78.1 +/- 5.9 years; 4 males and 7 females) normal subjects were compared. The elderly subjects have a slightly, but significantly higher mean basal systolic blood pressure (132.4 +/- 17.7 mmHg) than the young subjects (118.7 +/- 11.4 mmHg), but the basal diastolic and mean blood pressures of the two groups were similar. Intravenous bolus infusion of PTH(1-34) at a dose of 100 U induced transient, but marked hypotension in all subjects. The mean maximal decrease in systolic blood pressure (-delta SBP was significantly more (p less than 0.01) in the elderly subjects (42.5 +/- 13.9 mmHg) than in the young subjects (8.0 +/- 8.9 mmHg), but the maximal decrease in diastolic blood pressure (-delta DBP) was similar in the elderly (25.6 +/- 13.9 mmHg) and young (27.3 +/- 10.9 mmHg) subjects. The maximal decrease in the mean blood pressure (-delta MBP) was also significantly higher (p less than 0.01) in the elderly subjects (31.9 +/- 8.7 mmHg) than in young ones (20.6 +/- 7.6 mmHg). The corrected serum level of calcium (scCa) was significantly (p less than 0.01) lower in the elderly subjects (9.6 +/- 0.2 mg/dl) than in the young ones (10.0 +/- 0.3 mg/dl), and the serum level of C-terminal parathyroid hormone (C-PTH) was significantly higher in the elderly subjects (270 +/- 80 pg/ml) than in the young ones (150 +/- 80 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS) |
| 1989 | [Calcium-regulating hormones in primary arterial hypotension in children]. | Pediatriia | Radioimmunoassay was used to measure the content of parathyroid hormone and calcitonin in blood serum of 65 children aged 7 to 14 years suffering from arterial hypotension. The content of total calcium and phosphorus in serum was studied by spectrophotometry. In the majority of children with arterial hypotension, the content of calcium was significantly reduced, provided the disease ran a labile course. Disorders in the regulation of blood serum calcium may appear one of the factors giving rise to arterial hypotension in children. |
| 1988 | Hypotensive action of parathyroid hormone in hypoparathyroid and hyperparathyroid rats. | Hypertension | Experimental and clinical data suggest an association between chronic hyperparathyroidism and hypertension, but acute infusion of parathyroid hormone causes vasodilation and hypotension. These observations imply that chronic and acute parathyroid states affect blood pressure through different mechanism(s), either by modification of vascular receptors or by an ionophoretic effect of parathyroid hormone. The effect of parathyroid status induced by dietary calcium manipulations or by surgical ablation of the parathyroid gland on the hypotensive response of parathyroid hormone infusion was studied in rats. At 4 weeks of age 24 male rats were divided into four equal groups. Three groups were sham-operated, and one group was thyroparathyroidectomized. Only the thyroparathyroidectomized group was treated with thyroxine, 10 micrograms/kg/day. The control and thyroparathyroidectomized groups were raised on a 1.4% calcium diet; the other two groups were raised on 0.005% and 2.8% calcium diets. After 8 weeks on the diets, parathyroid hormone was infused through a venous cannula at 5 and 10 micrograms/kg doses and blood pressure was measured through arterial cannulas. The results indicate that hyperparathyroidism and hypocalcemia induced by the low calcium diet attenuated the hypotensive response to parathyroid hormone compared with responses in rats raised on a 1.4% calcium diet. In hypoparathyroid rats (2.8% Ca diet) with hypercalcemia, the hypotensive response was also reduced. However, in hypoparathyroid (thyroparathyroidectomized) rats with hypocalcemia, the hypotensive response was enhanced. The data suggest that chronic parathyroid status, as well as hypercalcemia, alters the hypotensive response to parathyroid hormone infusion, presumably by altering the vascular parathyroid hormone receptors or by some other mechanism. |
| 1988 | Parathyroid hormone impairs extrarenal potassium tolerance in the rat. | Am J Physiol | The effect of parathyroid hormone (PTH) on the extrarenal disposition of an acute potassium load was examined in acutely nephrectomized rats infused with KCl (0.75 meq.kg-1.h-1 for 90 min) alone or in combination with 8-10 U.kg-1.min-1 PTH, with serial monitoring of plasma potassium every 10 min. The rise in plasma potassium concentration (delta PK) in the PTH group was higher than control. PTH was then administered along with KCl to two groups of nephrectomized and acutely thyroparathyroidectomized (TPTX) rats in doses of 1 and 0.25 U.kg-1.min-1 for 90 min. delta PK with PTH in both groups was higher than TPTX control (P less than 0.01). The two higher doses of PTH resulted in a decrease in mean arterial pressure from their respective controls. A similar reduction in arterial pressure in three groups of nephrectomized rats by administration of hydralazine or nitroprusside or by acute blood loss did not change delta PK subsequent to potassium infusion from that in control rats. Furthermore, the lowest dose of PTH did not lower arterial pressure from its respective control. Therefore, hypotension is not a cause for the PTH-induced potassium intolerance. Serum levels of insulin, aldosterone, catecholamines, calcium, plasma HCO3 concentration, and pH were not different in PTH-infused vs. respective control rats. These data suggest that PTH impairs extrarenal potassium disposal in the rat. The effect of PTH may relate to enhanced calcium entry into cells. |
| 1988 | Autonomic nervous system in haemodialysis. | Nephrol Dial Transplant | Fifty-two patients with terminal chronic renal failure on haemodialysis were assessed for the existence of autonomic neuropathy using the Valsava index. The values in the patients were lower than in the controls. Only a few symptoms could be related to the autonomic neuropathy. No correlation was found between Valsalva index and orthostatic or intradialysis hypotension, motor-nerve conduction velocity or plasma intact parathyroid hormone. Having demonstrated the existence of autonomic neuropathy, eight healthy subjects and ten patients on haemodialysis were studied to locate the segment of the autonomic reflex are affected. Heart rate and intraarterial pressure were monitored during the following tests: phenylephrine; hyperventilation; cold pressor; atropine; tyramine and adrenaline. An alteration was observed in baroreceptors, together with adrenergic hyperexcitability (reflected in the hypersensitivity of the sympathetic efferent pathway) and a greater response to the stimulus for the release of extra-adrenal adrenaline. The lower response to atropine is indicative of vagal alteration. |
| 1987 | The multifactorial basis for hypocalcemia during sepsis. Studies of the parathyroid hormone-vitamin D axis. | Ann Intern Med | To learn about the pathogenesis of sepsis-associated hypocalcemia, we measured serum ionized calcium concentrations in 60 critically ill patients with bacterial sepsis; 12 (20%) had hypocalcemia. The mortality rate in the hypocalcemic patients with sepsis (50%) was higher than that in the normocalcemic patients with sepsis (29%). Only patients with gram-negative sepsis became hypocalcemic, and hypocalcemia contributed to hypotension in 7 of the 12 hypocalcemic patients. Serum calcium concentrations returned to normal in each of those patients with sepsis who survived. Hypocalcemia during sepsis occurred in previously normocalcemic patients and was multifactorial in origin, resulting from acquired parathyroid gland insufficiency, renal 1 alpha-hydroxylase insufficiency, vitamin D deficiency, and acquired calcitriol resistance. We conclude that the hypocalcemia of sepsis is associated with a high mortality rate and usually occurs in previously normocalcemic patients who acquire a defect in the parathyroid-vitamin D axis. |
| 1987 | Dose/response study of aminohydroxypropylidene bisphosphonate in tumor-associated hypercalcemia. | Am J Med | Bisphosphonates (or diphosphonates) constitute a major advance in the treatment of tumor-associated hypercalcemia and also have the potential to prevent or reverse osteolysis in normocalcemic patients. Available information on adequate therapeutic doses and potential toxicity is, however, very fragmentary. This report describes a phase I study of one of the most promising bisphosphonates currently available, aminohydroxypropylidene bisphosphonate (AHPrBP or APD), in tumor-associated hypercalcemia. Only patients remaining hypercalcemic after 48 hours of rehydration were evaluated, and antineoplastic therapy was delayed at least until a normal serum calcium level was reached. AHPrBP was given as two-hour daily infusions for three days, and three different patients were treated at each of the six following dosage levels: 0.01, 0.05, 0.25, 0.75, 1.5, and 3.0 mg/kg per day. The two lowest dosages levels were insufficient to normalize serum and urinary calcium levels, but the efficacy of the four other dosages was very similar. Plasma immunoreactive parathyroid hormone levels increased as a function of calcium levels, whereas urinary hydroxyproline levels did not prove to be a very useful measure of AHPrBP's effects on bone resorption. The drug was generally very well tolerated: only six patients had transient fever and/or decreases in lymphocyte count that were not clearly related to AHPrBP dosage. The only real problem was observed at the highest dosage of 3.0 mg/kg per day in an obese woman in whom high fever and hypotension developed. Efficacy and tolerance in dehydrated patients were verified by treating seven other patients, not previously rehydrated, at 1.0 mg/kg per day for three days. In summary, the therapeutic range of AHPrBP, given for three days as a two-hour infusion daily, lies between 0.25 and 1.5 mg/kg per day. Fasting urinary calcium levels are probably the most reliable and easily measured parameter to monitor AHPrBP's inhibition of bone resorption in normocalcemic patients. |
| 1984 | Structural prerequisites for the hypotensive action of parathyroid hormone. | Am J Physiol | We assessed the vascular, phosphaturic, and calcemic responses to several synthetic parathyroid hormone (PTH) analogues. Bovine (b) PTH (1-34), human (h) PTH (1-34), hPTH (53-84), [ Nle8 , Nle18 , Tyr34 ]bPTH (1-34), and [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) were administered in doses between 1 and 500 micrograms/kg as bolus intravenous injections to male Wistar-Kyoto rats aged 18-26 wk. Antagonism of the action of PTH was assessed in rats pretreated with 10 or 100 micrograms/kg [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) followed by 10 micrograms/kg of bPTH (1-34), or with 10 micrograms/kg hPTH (53-84) followed by 10 micrograms/kg hPTH (1-34). Bovine PTH (1-34), hPTH (1-34), and [ Nle8 , Nle18 , Tyr34 ]bPTH (1-34) produced virtually identical log dose-dependent hypotension, with 100 micrograms/kg of each analogue producing a 56% reduction in mean arterial pressure. Neither hPTH (53-84) nor [ Nle8 , Nle18 , Tyr34 ]bPTH (3-34) demonstrated any effect on mean arterial pressure at doses up to 500 micrograms/kg. Pretreatment with the inactive analogues failed to antagonize the vasodilating response to either bPTH (1-34) or hPTH (1-34). The vasoactive analogues significantly increased urinary phosphorus excretion while the inactive analogues did not modify it. hPTH (1-34) produced a modest decrease in serum Ca2+ at 1 min after injection. The results document that the vasodilating effect of PTH is a specific action of the peptide. Deletion of the first two amino acid residues abolishes both the phosphaturic and hypotensive effects of the peptide. Acute changes in serum Ca2+ do not appear to be a prerequisite for the vasodilatory response. Inactive analogues of PTH do not antagonize the vascular actions of the peptide. |
| 1983 | [Antihypertensive action of elcatonin]. | Nihon Yakurigaku Zasshi | Subcutaneous injections of elcatonin, a synthetic analogue of eel calcitonin, lowered the blood pressure in DOCA/saline-hypertensive and spontaneously hypertensive rats (SHR), but not in normotensive Wistar rats. The hypotensive effect was more prominent in the DOCA hypertensive rats. Daily injections of elcatonin (10-30 U/kg/day for 21 days) resulted in maximum hypotension on the 4th day in DOCA hypertensive rats and on the 14th day in SHR, and the reduced level of blood pressure was maintained. After the cessation of elcatonin injections, the pressure started to elevate gradually towards the control level. In normotensive rats, elcatonin did not significantly alter the blood pressure for 6 weeks. Daily injections of elcatonin significantly prevented the development of DOCA-induced hypertension and spontaneously-occurring hypertension. Elcatonin-induced hypotension did not differ in the control and parathyroidectomized DOCA hypertensive rats. Elcatonin did not alter the pressor response to noradrenaline, vasopressin and angiotensin II nor the depressor response to isoproterenol, acetylcholine and histamine in DOCA hypertensive rats. It is concluded that the antihypertensive effect of elcatonin is not associated with the release of parathyroid hormone nor with the blockade of alpha, beta, angiotensin II and vasopressin receptors. |
| 1983 | A case of advanced breast cancer associated with hypocalcemia. | Jpn J Clin Oncol | Although hypercalcemia is a well-known complication of malignant diseases, hypocalcemia seems to be a rather rare one. A 34-yr-old woman with advanced breast cancer who presented hypocalcemia is described. She had generalized multiple osteolytic bone metastases which were progressive in spite of chemo-endocrine and radiation therapy. She was admitted because of severe bone pain and dyspnea caused by bilateral pleural effusion. Laboratory examination on admission showed that the serum calcium was 9.6 mg/dl, serum total protein 5.9 g/dl, serum inorganic phosphorus 4.6 mg/dl, and serum alkaline phosphatase 29.6 King-Armstrong units. The serum calcium gradually fell to 7.0 mg/dl on the 45th hospital day when the serum total protein was 6.8 g/dl and she complained of paresthesia in the extremities. On the 58th day, severe tachycardia and hypotension developed and she died of congestive heart failure on the 67th hospital day. At that time the serum calcium was 5.4 mg/dl. During her hospital course, the plasma parathyroid hormone levels were examined repeatedly and were 0.4, 0.6, 0.6 and 0.7 ng/ml (normal; less than 0.5 ng/ml). Autopsy revealed that cancer invaded the space between the thyroid and the trachea and no parathyroid glands could be found even in the mediastinum. Microscopically the parathyroid glands were replaced completely by the cancer cells. These observations indicate that metastasis of breast cancer to the parathyroid glands caused relative hypoparathyroidism, resulting in hypocalcemia. In addition, congestive heart failure which was refractory to digitalis and diuretics might have been caused by impaired contractility of the myocardium associated with hypocalcemia. |
| 1982 | Application of newly synthesized 1-34 human parathyroid hormone for diagnostic tests. | Pharmatherapeutica | 1-34 human parathyroid hormone (1-34 hPTH) was synthesized by a liquid-phase method and prepared for clinical use (specific activity, 3281 U/mg). With this preparation, the toxicity was studied in 22 normal volunteers and the metabolic effects in 15 individuals. Intradermal administration of 4 ng of 1-34 hPTH caused neither abnormal local skin reactions nor toxicity in terms of subjective and objective parameters. When administered intravenously at doses of from 2 to 20 microgram as a bolus, the preparation caused no acute or subacute toxicity judging from the results of various clinical and laboratory studies, except for transient mild hypotension and headache in a minority of subjects. For diagnostic use, 20 microgram of 1-34 hPTH administered intravenously was found to produce effects almost equivalent to those of 200 USPU U of Parathormone (PTE, Eli Lilly). Thus, the criteria for differentiation of hypoparathyroidism from pseudo-hypoparathyroidism devised with 2000 USP U of PTE as a test substance was found to be applicable when 20 microgram of 1-34 hPTH was utilized. |
| 1980 | Effects of synthetic parathyroid hormone on vascular beds of dogs. | Pharmacology | Blood flow rates and vascular resistance in dogs were determined in 14 tissues with 15 +/- 2 microns radioactive microspheres (141Ce, 51Cr, 85Sr). Intravenous injections of synthetic bovine parathyroid hormone containing the NH2-terminal 1--34 amino acids [bPTH-(1--34)] at the dose of 10 USP units/kg body weight produced hypotension and increases in blood flow rate and decreases in resistance in kidney cortex, kidney medulla, heart, liver, stomach and pancreas at 1/2 and 2 min after injection. 4 U bPTH-(1--34)/kg body weight produced less vasodilation. Saline injection had no effect on the tissues studied. |
| 1980 | Hypotensive action of parathyroid hormone preparations on rats and dogs. | Proc Natl Acad Sci U S A | Bovine parathyroid extract and two commercial preparations containing the first 34 amino acids of synthetic bovine parathyroid hormone [bPTH-(1-34)]produced dose-related hypotension in anesthetized rats. Dogs were 10 times more sensitive to the two bPTH-(1-34) preparations than were rats. Propranolol, phentolamine, atropine, and promethazine did not affect the hypotensive action of bPTH-(1-34) in rats and dogs. bPTH-(1-34) decreased perfusion pressure in rat hindlimbs perfused in situ with Ringer's solution and was a vasodilator in dog kidneys perfused in vitro with Ringer's solution. Helical strips of rabbit aorta were also relaxed by bPTH-(1-34). We conclude that the direct vasodilatory action of bPTH preparations represents an intrinsic property of parathyroid hormone and that the hypotensive effect of this hormone is produced by part or all of the first NH2-terminal 34 amino acids. |
| 1978 | Renin release by parathyroid hormone in the dog. | Endocrinology | Synthetic N-terminal 34 amino acid peptide of bovine parathyroid hormone (PTH) produced a consistent rise in plasma renin activity in saline-loaded dogs when given iv either as a single bolus dose of 400 U or infused steadily in lower dosage over a number of hours. Infusion of as little as 1 U/min produced a significant rise in plasma renin activity, but a greater effect was obtained with 2 U/min. Infusion of 4 U/min had no more effect than 2 U/min. In contrast to transient hypotension after rapid injection of a single large dose, blood pressure did not change significantly during the steady infusion of lower doses of PTH. These findings are compatible with the thesis that an increased distal tubular load of sodium stimulates renin release and suggest that the increased distal sodium absorption after the proximal effects of PTH may be regulated by the renin-angiotensin-aldosterone system. |
| 1976 | Derman necrosis due to thrombosis in severe secondary hyperparathyroidism. | Arch Intern Med | Two patients had gangrenous dermal necrosis associated with chronic renal disease and secondary hyperparathyroidism. Thromobosed and heavily calcified small arteries were underlying the infarcted areas. One patient had severe hypotension secondary to hemorrhage, which immediately preceded the appearance of dermal lesions. Both patients had notably elevated serum parathyroid hormone and serum alkaline phosphatase levels, as well as severe hyperphosphatemia. Therapy with phosphate binders and calcium and vitamin D supplementation corrected the hyperphosphatemia and reduced serum alkaline phosphatase levels. One patient died; the other patient's dermal lesions healed completely. Localized thrombosis, rather than obliterative intimal proliferation, represents a unique cause of dermal necrosis in this condition. |