Chronotherapy of high-dose active vitamin D3 in haemodialysis patients with secondary hyperparathyroidsm: a repeated dosing study.
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AIMS: Renal osteodystrophy is the major complication in patients with end-stage renal failure. Oral or intravenous vitamin D3 (D3) is given to these patients, but severe hypercalcaemia sometimes interrupts this therapy. This study was undertaken to determine whether the effectiveness and safety of D3 also depend on its dosing time during a repeated treatment. METHODS: A higher dose (3 micro g) was given orally to 13 haemodialysis patients at 08.00 h or 20.00 h for 12 months by a randomized, cross-over design. RESULTS: Three patients were withdrawn due to severe hypercalcaemia after switching from 08.00 h to 20.00 h dosings. The elevation in serum calcium concentration was significantly (P < 0.001) greater during the 08.00 h dosing in the remaining ten patients. Mean serum Ca concentration after the trial was 10.92 (95% confidence interval (CI) 10.79, 11.06) and 9.55 mg dl-1 (95% CI 9.30, 9.71) by 08.00 h and 20.00 h dosing, respectively. On the other hand, the suppression of the elevated serum parathyroid hormone (PTH) and subsequent increment in bone density were significantly greater during the 08.00 h dosing. Mean PTH concentration after the trial was 414 (95% CI 360, 475) and 220 pg ml-1 (95% CI 202, 249) by 08.00 h and 20.00 h dosing, respectively (P = 0.02). Mean increment of bone density after the trial was 22 (95% CI 8, 32) and 57 g cm-3 (95% CI 43, 83) by 08.00 h and 20.00 h dosing, respectively (P = 0.04). CONCLUSION: These results indicate that a higher dose of oral D3 is more effective and safe after dosing at evening in patients with renal osteodystrophy. (+info)
Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy.
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BACKGROUND: Elevated calcium and phosphorus levels after therapy with injectable vitamin D for secondary hyperparathyroidism may accelerate vascular disease and hasten death in patients undergoing long-term hemodialysis. Paricalcitol, a new vitamin D analogue, appears to lessen the elevations in serum calcium and phosphorus levels, as compared with calcitriol, the standard form of injectable vitamin D. METHODS: We conducted a historical cohort study to compare the 36-month survival rate among patients undergoing long-term hemodialysis who started to receive treatment with paricalcitol (29,021 patients) or calcitriol (38,378 patients) between 1999 and 2001. Crude and adjusted survival rates were calculated and stratified analyses were performed. A subgroup of 16,483 patients who switched regimens was also evaluated. RESULTS: The mortality rate among patients receiving paricalcitol was 3417 per 19,031 person-years (0.180 per person-year), as compared with 6805 per 30,471 person-years (0.223 per person-year) among those receiving calcitriol (P<0.001). The difference in survival was significant at 12 months and increased with time (P<0.001). In the adjusted analysis, the mortality rate was 16 percent lower (95 percent confidence interval, 10 to 21 percent) among paricalcitol-treated patients than among calcitriol-treated patients. A significant survival benefit was evident in 28 of 42 strata examined, and in no stratum was calcitriol favored. At 12 months, calcium and phosphorus levels had increased by 6.7 and 11.9 percent, respectively, in the paricalcitol group, as compared with 8.2 and 13.9 percent, respectively, in the calcitriol group (P<0.001). The two-year survival rate among patients who switched from calcitriol to paricalcitol was 73 percent, as compared with 64 percent among those who switched from paricalcitol to calcitriol (P=0.04). CONCLUSIONS: Patients who receive paricalcitol while undergoing long-term hemodialysis appear to have a significant survival advantage over those who receive calcitriol. A prospective, randomized study is critical to confirm these findings. (+info)
Pathogenesis and treatment of renal osteodystrophy.
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Renal osteodystrophy is the term used to describe the many different patterns of the skeletal abnormalities that occur in patients with chronic kidney disease. The main two conditions are osteitis fibrosa, characterized by high bone turnover, increased osteoclastic and osteoblastic activity, and high levels of circulating parathyroid hormone (PTH) and adynamic bone disease characterized by low bone turnover and low levels of circulating PTH. Retention of phosphorus, decreased levels of calcitriol in blood, decreased levels of serum ionized calcium, reduced numbers of vitamin D receptors and calcium sensors in the parathyroid gland, and skeletal resistance to the calcemic action of PTH play a major role in the development of renal osteodystrophy. This review will describe the current approach for the treatment of renal osteodystrophy. (+info)
Chronic renal failure. Its effect on calcium, phosphorus and osseous metabolism unified approach.
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The renal osteodystrophies represent the metabolic consequences of (1) vitamin D resistance, (2) secondary hyperplasia of the parathyroids, and (3) the changes in serum PO(4)= and Ca++ secondary to the renal insufficiency per se. The osseous lesion in any given patient with chronic renal failure may be osteitis fibrosa, rickets (osteomalacia), calcium deficiency osteoporosis or any combination of these. The concentration of Ca++ and PO(4)= in the serum is determined by the degree of renal failure and the skeletal response to parathyroid hormone. (+info)
Serum aluminum levels as a reflection of renal osteodystrophy status and bone surface aluminum staining.
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Twenty eight (14%) out of 196 patients in a regional dialysis population were found to have serum aluminum levels greater than or equal to 5 mumol/L or 135 micrograms/L; 21 consented to undergo a bone biopsy to identify the spectrum of renal osteodystrophy associated with this degree of hyperaluminemia. Both the Aluminon reagent and the acid solochrome azurine (ASA) stain were used to identify aluminum deposits. A control group of 13 patients with biochemical and histological evidence of severe secondary hyperparathyroidism was used to contrast the measured parameters of bone histology in the hyperaluminemic group. Al(OH)3 was used as the principal phosphate binder in all patients. In the hyperaluminemic group, 67% had either dialysis osteomalacia or aplastic bone lesions, and all except one aplastic lesion were positive for bone surface aluminum deposits by the Aluminon stain. The Aluminon stain was also positive in one of three cases of osteitis fibrosa and three of four mild lesions, whereas it was negative in all biopsies from the control group. However, the ASA stain was positive in all biopsies from the hyperaluminemic group and in 11 of 13 control biopsies from the patients with "pure" osteitis fibrosa. For all biopsy data from both groups, there were significant (P less than 0.01) negative correlations between the ASA-stained surface aluminum deposits and resorption indices (total eroded surface, r = -0.68; surface osteoclast counts, r = -0.53) and indices of bone formation (surface osteoblast counts, r = -0.61; mineral apposition rate, r = -0.63; bone formation rate, r = -0.69). These correlations were not significant for Aluminon-stained surface deposits with the exception of the bone formation indices, which had lower correlation coefficients (r = -0.44). These data suggest that hyperaluminemia greater than or equal to 5 mumol/L has a predictive value to identify impaired mineralization in dialysis patients that is high enough to affect clinical decision making. However, the more sensitive ASA stain identifies surface aluminum across the whole spectrum of renal osteodystrophy and is consistent with a toxic role for aluminum at any level of exposure. (+info)
Selected indicators of bone metabolism in patients after kidney transplant.
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Bone metabolism defects and skeleton diseases, so called renal osteopathy (RO), represent very serious clinical problems in the care of patients with kidney dysfunction. Renal osteopathy is a complicated skeletal disorder with a very complicated pathogenesis and we can encounter its individual forms in kidney transplant patients. (+info)
Biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialyzed children.
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In this study we investigated the value of biochemical markers of bone turnover in the diagnosis of renal osteodystrophy in dialysis patients. The study was carried out in 22 chronic renal failure patients (mean age: 16.1 +/- 4.5) being treated with chronic dialysis. There were three groups according to intact parathormone (iPTH) levels: Group I (n: 6): iPTH levels were less than 200 pg/ml; Group II (n: 9): iPTH levels were between 201 and 500 pg/ml; and Group III (n: 7). iPTH levels were higher than 501 pg/ml. We investigated iPTH, bone alkaline phosphatase, total serum alkaline phosphatase, osteocalcin, serum type 1 procollagen peptide (PICP) and insulin-like growth factor-1 (IGF-1) levels in all patients. In group III mean bone alkaline phosphatase level (126.0 +/- 10.95) was significantly higher than in both group I and group II (52.16 +/- 22.8, 57.35 +/- 16.21) (p < 0.001). Mean osteocalcin level (35.13 +/- 2.93) in group I was significantly lower than in group III (40.52 +/- 2.83) (p < 0.05). Serum alkaline phosphatase, PICP and IGF-1 levels were not different between the groups (p > 0.05). There was a significant positive correlation between bone alkaline phosphatase and iPTH (r = 0.80, p < 0.0001). Serum osteocalcin correlated with both bone alkaline phosphatase and iPTH (correlation) coefficients were r = 0.44 and r = 0.51 respectively, p < 0.05). It is concluded that bone alkaline phosphatase and osteoocalcin combined with iPTH level seem to be useful noninvasive markers of bone metabolism in dialysis patients. (+info)
The importance of bone health in end-stage renal disease: out of the frying pan, into the fire?
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In the early stages of renal failure, hyperparathyroidism develops as a compensatory mechanism to control serum levels of calcium, phosphorus and calcitriol. As kidney disease progresses, this ability to maintain mineral homeostasis is lost, leading to the development of renal osteodystrophy (ROD). Over the past decade, the pattern of ROD seen in patients with chronic kidney disease (CKD) has changed. Previously, the majority of patients had mixed uraemic osteodystrophy or aluminium-related osteomalacia. The decreased use of aluminium-based phosphate binders, coupled with improvements in the management of hyperphosphataemia, led to a reduction in the prevalence of these types of ROD. Since the mid-1990s, there has been an increase in the prevalence of adynamic bone disease as a result of increased suppression of parathyroid hormone through the use of calcium-based phosphate binders and calcitriol therapy. Adynamic bone disease is also associated with several clinical factors, such as older age, use of continuous ambulatory peritoneal dialysis and the presence of diabetes mellitus, as well as the use of calcitriol therapy. Studies of calcium metabolism in patients with CKD have shown that adynamic bone disease is a distinct clinical condition that leads to hypercalcaemia via mechanisms different from that seen in high-turnover bone disease. As high calcium x phosphorus product has been associated with soft tissue and vascular calcifications, and increased mortality, optimizing bone health may be an important way of reducing cardiovascular risk in patients with CKD. To do this, novel, effective, non-calcium, non-aluminium phosphate binders will be necessary. (+info)