Influence of sevelamer hydrochloride on serum concentration of whole (1-84) and N-terminally truncated (7-84) parathyroid hormone fragments in hemodialysis uremic patients

Phosphate retention stimulates parathyroid hormone (PTH) secretion in uremic patients. Sevelamer hydrochloride is an aluminium- and calcium-free phosphate binder used in the treatment of secondary hyperparathyroidism in uremic patients. The influence of the phosphate lowering effect on serum levels of whole PTH-1-84 and N-terminally truncated PTH-7-84 has not been studied. Seventeen hemodialysis (HD) patients (nine male, eight female) with chronic renal failure and serum phosphorus concentrations, despite calcium carbonate treatment, >2.0 mmol/L were enrolled in this study. Patients did not receive aluminium containing binders. Blood samples for serum concentration assessments of calcium, phosphorus, PTH-1-84 and N-terminally truncated PTH-7-84, carboxyterminal cross-linked collagen fragments (Ctx), total (AP) and bone specific alkaline phosphatase activity (BAP) were drawn twice: before and after 5-week sevelamer administration (in addition to calcium carbonate). Sevelamer treatment was followed by a significant reduction in serum phosphorus level (from 2.46 +/- 0.09 to 2.07 +/- 0.10 mmol/L; p=0.009), PTH-1-84 level (from 396 +/- 75 to 298 +/- 64 pg/mL; p=0.03) and PTH-1-84/PTH-7-84 ratio (from 1.78 +/- 0.18 to 1.55 +/- 0.19; p=0.01), while serum PTH-7-84 levels declined only slightly (from 220 +/- 35 to 183 +/- 25 pg/mL; p=0.11). Serum calcium, Ctx concentrations, AP and BAP activity did not change markedly. There was a significant positive correlation between changes of phosphorus and PTH-1-84 (tau=0.48; p=0.007) or PTH-7-84 concentration (tau=0.43; p=0.02). A 5-week sevelamer treatment suppressed both PTH-1-84 (change statistically significant) and PTH-7-84 (change statistically non-significant) serum concentration in HD uremic patients seemingly related to changes in phosphatemia.     

Intracranial surgery under hemodialysis (author's transl)

A case of pituitary adenoma operated on under hemodialysis was reported. The patient was a 43-year-old male who had been obliged to hemodialysis since April 1975 because of chronic renal failure. He was admitted in February 21, 1976 because of progressive visual symptoms. Neurological examination revealed decreased visual acuity and bitemporal hemianopsia. Radiology showed enlarged sella turcica and calcified mass in the suprasellar region. Laboratory examination disclosed severe anemia and the operation was postponed until the hematocrit improved up to 39% by blood transfusion. The operation was performed in March 17, 1976 under conventional GOF anesthesia. The tumor was covered by a calcified capsule and after nibbling off the calcified covering, the tumor was removed. Postoperative course was uneventful. Peritoneal dialysis was continued for three days immediately after operation. Urinary volume of the patient increased up to 600 ml per day after operation, probably due to the postoperative diabetes insipidus. The diabetes insipidus was rather favorable sequela in this case because the patient was released from the severe restriction of water intake.     

Haemodialysis in patients with pre- andpostoperative acute renal failure (author's transl)

Treatment and management of patients with renal insufficiency before and after surgery is often complicated. Early interdisciplinary cooperation between intensive care specialist, surgeon, gynaecologist, urologist and nephrologist is necessary. The mortality rate of patients with acute renal failure is still high (50 to 60%). The increase in patients with chronic renal failure who are in need of haemodialysis involves more surgical procedures in this group even in future.     

Differential effects of intermittent PTH(1-34) and PTH(7-34) on bone microarchitecture and aortic calcification in experimental renal failure

PTH(1-84) and PTH(7-84) are elevated in chronic kidney disease (CKD). These peptides, as their shorter analogs PTH(1-34) and PTH(7-34) both promote PTH receptor (PTH1R) internalization but only PTH(1-34) and PTH(1-84) activate the receptor. Here, we examined the effects of intermittent administration of PTH(1-34) and PTH(7-34) on mineral ion metabolism, bone architecture, and vascular calcification in rats with experimental CKD. CKD with or without parathyroidectomy (PTX) was established by 5/6 nephrectomy (NPX) in rats. Animals were divided into 4 groups: Sham PTX+ sham NPX (Sham); PTX+ sham NPX (PTX); Sham PTX+NPX (NPX); PTX+NPX (PTX/NPX). Rats were treated with single daily doses of 40 microg/kg PTH(1-34), PTH(7-34), or vehicle. Creatinine was higher in NPX and Ca lower in PTX and PTX/NPX groups than in Sham or NPX rats. Plasma phosphate was higher in PTX, NPX and PTX/NPX than in Sham rats. PTH(1-34) was more hypercalcemic than PTH(7-34) in PTX rats. Fractional bone volume in rats treated with PTH(1-34) increased significantly in all groups compared to that of vehicle treatment. In addition, trabecular number, thickness and volumetric bone density increased in rats treated with PTH(1-34). In contrast, PTH(1-34) diminished vascular calcification. Bone and renal PTH1R mRNA expression was reduced as much or more in PTX/NPX rats as in NPX alone, whereas PTH(7-34) had no effect on PTH1R expression. Renal but not bone PTH1R mRNA increased in response to PTH(1-34). These findings suggest that PTH(1-34) exerts greater hypercalcemic and anabolic effects in parathyroidectomized and/or nephrectomized rats than does PTH(7-34). There was no evidence for significant bone or vascular actions of PTH(7-34). We conclude that PTH(1-34) protects against vascular calcification and bone demineralization in experimental renal failure.     

Effect of hemodialysis and renal failure on serum biochemical markers of bone turnover

The aim of the present study was to evaluate the effect of hemodialysis and renal failure on serum bone markers. Serum total alkaline phosphatase (TAP), procollagen type I aminoterminal propeptide (PINP), and -carboxyterminal telopeptide of type I collagen (-CTX), as well as intact parathyroid hormone (iPTH), creatinine, and total protein were measured in 14 patients with endstage renal disease (ESRD) before and at 1, 2, and 4h during a hemodialysis session, and at the same sampling interval in 6 renal transplant recipients. The results were compared to those obtained in 20 healthy adults. All patients showed increased baseline mean values of PINP, -CTX, and iPTH. -CTX differed significantly between hemodialysis patients and renal transplant recipients. TAP and -CTX were the only markers which correlated with iPTH (P 0.05) and creatinine values (P 0.001), respectively. Renal transplant recipients did not show significant variations in the evolution of mean values of bone markers throughout the study, whereas, during the dialysis period, all the bone markers analyzed in the study showed a significant change. The change differed depending on the marker considered: -CTX showed a significant decrease at the end of the session, TAP increased at this time and, although PINP showed an initial increase during hemodialysis, no significant changes were observed at the end of the session. We conclude that bone markers are significantly influenced by hemodialysis, especially serum TAP and -CTX. ESRD is associated with an increase in these bone markers, in some cases related to iPTH values and in others to glomerular function. These findings should be taken into account when evaluating bone markers in these patients.     

Acute posttraumatic renal failure following therapy with antibiotics and beta-aescin (author's transl)

A case of acute renal insufficiency after therapy with gentamycin and beta-Aescin is reported. The role of these two agents in the causation of the acute renal failure is discussed. Renal function was restored using the REDY-Hemodialization System.     

Efficacy of whole PTH assay and 1-84/non-(1-84) PTH ratio in patients on hemodialysis or undergoing parathyroidectomy

For measurement of parathyroid hormone (PTH), the intact PTH (I-PTH) assay is generally used. However, I-PTH assay apparently detects PTH 7-84 fragments, in addition to PTH 1-84. The whole PTH (W-PTH) assay exhibits no cross-reactivity with PTH 7-84. Ratio of PTH 1-84 to non-(1-84) PTH has been proposed as a non-invasive indicator of bone turnover in patients with end-stage renal disease (ESRD). We evaluated the efficacy of W-PTH assay and 1-84/non-(1-84) PTH ratio in hemodialysis patients and patients who had undergone parathyroidectomy. PTH levels were measured using W-PTH and I-PTH assays in 138 hemodialysis patients, 27 healthy controls and 10 patients who were scheduled to undergo parathyroidectomy for secondary hyperparathyroidism. Alkaline phosphatase, bone alkaline phosphatase and intact osteocalcin were also measured for comparison with 1-84/non-(1-84) PTH ratio. W-PTH was strongly correlated with I-PTH in both groups, and with all three bone metabolic markers in hemodialysis patients. In hemodialysis patients, both PTH and bone metabolic markers were significantly lower in the subgroup with a PTH ratio < 1.0 than in the subgroup with a PTH ratio > or = 1.0. However, PTH ratio exhibited no significant correlation with bone metabolism markers. PTH ratio was higher after parathyroidectomy than before. W-PTH and I-PTH assays offer identical indicators of bone metabolism in ESRD patients. However, 1-84/non-(1-84) PTH ratio may be of limited diagnostic use regarding bone turnover if a cut-off value of 1.0 is used. PTH 1-84 may be secreted relatively more than non-(1-84) PTH after parathyroidectomy, due to decreases in serum calcium. As the W-PTH assay allows easy calculation of non-(1-84) PTH by subtracting the I-PTH value, this assay contributes to identification of the function of non-(1-84) PTH fragments in various conditions.