Left ventricular hypertrophy: is hyperphosphatemia among dialysis patients a risk factor?
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Cardiovascular disease occurs in ESRD patients at rates that are far higher than is seen in the general population, and cardiovascular deaths account for the majority of deaths among dialysis patients. Abnormal mineral metabolism is a novel cardiovascular risk factor among dialysis patients. Recently published results demonstrated that even with good control of BP and anemia, conventional hemodialysis is associated with significant left ventricular hypertrophy (LVH); however, daily hemodialysis was associated with a significant reduction in LV mass index (LVMI). Furthermore, it was shown that control of serum phosphorus correlates with the reduction in LVMI. These data suggest a novel mechanism for the deleterious effect of elevated serum phosphorus on cardiovascular outcomes among hemodialysis patients: LVH. Other investigators have noted an association of hyperphosphatemia and LVH; however, this study was the first to demonstrate that improvement in serum phosphorus is associated with reduction in LVM. In addition, it is shown that daily hemodialysis is an effective modality in improving serum phosphorus through significantly improved phosphorus removal. Elevated serum phosphorus leads to vascular calcification, which can lead to LVH by decreasing vascular compliance. However, our study showed an improvement in LVMI during a 12-mo period. Because vascular calcification is unlikely to remit over this time period, it is proposed that serum phosphorus has a reversible, cardiotoxic effect that leads to LVH that can be reversed successfully with good control of serum phosphorus. (+info)
How fibroblast growth factor 23 works.
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There is a discontinuum of hereditary and acquired disorders of phosphate homeostasis that are caused by either high or low circulating levels of the novel phosphaturic hormone fibroblastic growth factor 23 (FGF23). Disorders that are caused by high circulating levels of FGF23 are characterized by hypophosphatemia, decreased production of 1,25-dihydroxyvitamin D, and rickets/osteomalacia. On the other end of the spectrum are disorders that are caused by low circulating levels of FGF23, which are characterized by hyperphosphatemia, elevated production of 1,25-dihydroxyvitamin D, soft tissue calcifications, and hyperostosis. Knowledge of the genetic basis of these hereditary disorders of phosphate homeostasis and studies of their mouse homologues have uncovered a bone-kidney axis and new systems biology that govern bone mineralization, vitamin D metabolism, parathyroid gland function, and renal phosphate handling. Further understanding of this primary phosphate homeostatic pathway has the potential to have a significant impact on the diagnosis and treatment of disorders of bone and mineral metabolism. (+info)
High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients.
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BACKGROUND: Hyperphosphataemia is associated with increased mortality in patients with chronic kidney disease (CKD) stage IV or on dialysis. Furthermore, in animal studies, elevated plasma phosphate has been shown to be associated with an accelerated decline in renal function. The aim of this study was to determine the association of plasma phosphate with renal function loss and mortality in CKD stage IV-V pre-dialysis patients with GFR <20 ml/min/1.73 m(2). METHODS: Incident pre-dialysis patients were included between 1999 and 2001 in the multi-centre PREPARE study, and followed until 2003 or death. Rate of decline in renal function for each patient was calculated by linear regression using the Modification of Diet in Renal Disease (MDRD) formula to estimate GFR (eGFR). RESULTS: A total of 448 patients were included [mean (SD) age 60 (15) years, eGFR 13 (5.4) ml/min/1.73 m(2), decline in renal function 0.38 (0.95) ml/min/month]. Phosphate concentration at baseline was 4.71 (1.16) mg/dl, calcium 9.25 (0.77) mg/dl and calcium-phosphate product 43.5 (10.9) mg(2)/dl(2). For each mg/dl higher phosphate concentration, the mean (95% CI) decline in renal function increased with 0.154 (0.071-0.237) ml/min/month. After adjustment, this association remained [beta 0.178 (0.082-0.275)]. Seven percent of the patients died. Crude mortality risk was 1.25 (0.85-1.84) per mg/dl increase in phosphate, which increased to 1.62 (1.02-2.59) after adjustment. CONCLUSIONS: High plasma phosphate is an independent risk factor for a more rapid decline in renal function and a higher mortality during the pre-dialysis phase. Plasma phosphate within the normal range is likely of vital importance in pre-dialysis patients. (+info)
Economic evaluation of sevelamer in patients with end-stage renal disease.
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BACKGROUND: There is uncertainty about the most cost-effective way to treat hyperphosphataemia in patients with end-stage renal disease. Methods. We performed an economic analysis which compared the use of sevelamer with calcium carbonate in a simulated cohort of North American dialysis patients, using the perspective of the health care purchaser and a lifetime horizon. Outcomes considered were quality-adjusted life years (QALYs) gained and health care costs. To account for uncertainty, we considered four separate modelling strategies, obtaining data on the relative effectiveness of sevelamer from the recent Dialysis Clinical Outcomes Revisited study. RESULTS: In the base analysis, the use of sevelamer was associated with a cost per QALY gained of CAN$157,00, compared with calcium carbonate. Assuming no survival or hospitalization advantage for sevelamer, use of sevelamer resulted in an incremental cost of CAN$17,00 per patient. In alternate models which assumed sevelamer to be more effective than calcium-based phosphate binders, the use of sevelamer was associated with a cost per QALY gained ranging from CAN$127,00-$278,00. Assuming that sevelamer resulted in a differential reduction in mortality in patients > or = 65 years of age, use of sevelamer in this subgroup was associated with a cost per QALY of CAN$105,500. Results were similar in groups defined by age > or = 55 or by > or = 45 years. Since dialysis is expensive, interventions for dialysis patients that improve survival without reducing the need for dialysis will be associated with a cost-utility ratio at least as great as that of dialysis itself. As such, we repeated the primary analysis excluding the costs of dialysis and transplantation and found that the cost per QALY gained for sevelamer was $77,600. CONCLUSIONS: The cost per QALY gained for treating all dialysis patients with sevelamer exceeds what would usually be considered good value for the money. While the high cost per QALY was in part due to the inclusion of the costs of dialysis and transplant in the analysis, the cost per QALY gained remained relatively unattractive even when these costs were excluded. Although a lower cost per QALY gained is realized when only patients older than 65 years are treated, this strategy remains economically unattractive, particularly given the uncertainty of clinical benefit in this group. (+info)
Systematic review of the clinical efficacy and safety of sevelamer in dialysis patients.
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BACKGROUND: The relative effectiveness and safety of sevelamer for treatment of hyperphosphataemia in dialysis patients is uncertain, as compared with calcium-based phosphate binders. METHODS: We conducted a comprehensive search to identify all randomized cross-over or parallel group studies comparing sevelamer to any other therapy or placebo in adult dialysis patients. Study quality was assessed using the Chalmers Index. Data was extracted and checked using a standardized form and combined using a random effects model. RESULTS: We identified 14 primary publications of randomized trials (3193 participants) that were eligible for efficacy analysis. In analyses pooling, the 10 studies reporting on serum phosphate and calcium (2501 participants), serum phosphate was significantly lower with calcium-based phosphate binders by 0.12 mmol/l [95% confidence interval (CI) 0.05-0.19], compared with sevelamer. On-treatment calcium-phosphate product was not significantly lower in patients receiving calcium-based phosphate binders (0.12 mmol(2)/l(2), -0.05 to 0.29), compared with sevelamer. Overall mean difference in serum calcium was significantly lower with sevelamer therapy by 0.10 mmol/l (-0.12 to -0.07) and pooled on-treatment decrease in serum bicarbonate was significantly greater with sevelamer therapy by 2.8 mmol/l (2.2 to -3.5). In the five trials which reported all-cause mortality (2429 participants), the overall risk difference for all cause mortality in these five trials was similar between therapies (-2%, 95% CI -6-2). In the three trials which reported serious adverse events (2185 participants), there was a trend towards a lower risk in patients receiving calcium-based phosphate binders (13% lower, 95% CI -2-29). CONCLUSIONS: Compared with calcium-based phosphate binders, use of sevelamer in dialysis patients is associated with similar to slightly higher phosphate levels, similar calcium phosphate product, and slightly lower serum calcium levels. There was no evidence that sevelamer reduced all-cause mortality, cardiovascular mortality, the frequency of symptomatic bone disease or health-related quality of life. (+info)
Intraperitoneal calcitriol in infants on peritoneal dialysis.
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BACKGROUND: Calcitriol has long been used as the main therapy in renal osteodystrophy, but the efficacy of the oral route is not always as high as expected. OBJECTIVE: To asses the safety and efficacy of intraperitoneal calcitriol in infants undergoing peritoneal dialysis (PD). PATIENTS AND METHODS: PD patients on oral calcitriol therapy, with serum parathyroid hormone (PTH) >1000 pg/mL during the previous 3 months of treatment, were switched to intraperitoneal calcitriol therapy, 1 microg twice per week. Dose was increased to 1 microg three times per week if PTH remained >1000 pg/mL, and was later readjusted. Target PTH was 200-300 pg/mL according DOQI guidelines. STATISTICS: All results are expressed as mean +/- SE. The Wilcoxon signed rank test was used to evaluate differences in measurements for each pair of values. The confidence interval for differences between population medians was 96.9%. A p value less than 0.05 was considered significant. RESULTS: Six male children, mean age 17 +/- 3.86 months, completed a 12-month follow-up. Mean pretreatment PTH was 1654 +/- 209 pg/mL. Mean PTH at months 0, 3, 6, 9, and 12 was 1448 +/- 439*, 1277 +/- 723, 910 +/- 704, 582 +/- 282*, and 465 +/- 224* pg/mL, respectively (*p < 0.05). Twelve hypercalcemic and 10 hyperphosphatemic episodes were successfully treated. CONCLUSION: Infants on PD who fail to respond to oral calcitriol therapy can be safely treated with intraperitoneal administration of active vitamin D. (+info)
Sevelamer hydrochloride in peritoneal dialysis patients: results of a multicenter cross-sectional study.
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BACKGROUND: Sevelamer hydrochloride is a phosphate binder widely employed in hemodialysis patients. Until now, information about its efficacy and safety in peritoneal dialysis patients has been scarce. PATIENTS AND METHODS: In September 2005 a cross-sectional study of demographic, biochemical, and therapeutic data of patients from 10 peritoneal dialysis units in Catalonia and the Balearic Islands, Spain, was conducted. RESULTS: We analyzed data from 228 patients. At the time of the study, 128 patients (56%) were receiving sevelamer. Patients receiving sevelamer were younger (p < 0.01), showed a longer period of time on dialysis (p < 0.01), and had a lower Charlson Comorbidity Index (p < 0.01). Serum calcium and intact parathyroid hormone levels were not different between the two groups, while phosphate levels <5.5 mg/dL were observed more frequently in patients not receiving sevelamer (79% vs 61%, p < 0.01). Serum total cholesterol (167 +/- 41 vs 189 +/- 42 mg/dL, p < 0.01) and low density lipoprotein (LDL) cholesterol (90 +/- 34 vs 109 +/- 34 mg/dL, p < 0.01), but not high density lipoprotein cholesterol or triglycerides, were lower in sevelamer-treated patients. Moreover, sevelamer-treated patients displayed a higher serum albumin (38 +/- 5 vs 36 +/- 4 g/L, p < 0.01) and a lower C-reactive protein (4.9 +/- 12.8 vs 8.8 +/- 15.7 mg/L, p < 0.01). Blood bicarbonate levels <22 mmol/L were observed more frequently in patients receiving sevelamer (22% vs 5%, p < 0.01). Logistic regression analysis adjusting by confounding variables confirmed that sevelamer therapy was associated with serum total cholesterol <200 mg/dL [relative risk (RR): 2.77, 95% confidence interval (CI): 1.44 - 5.26, p = 0.002] and blood bicarbonate <22 mmol/L (RR: 8.5, 95% CI: 2.6 - 27.0, p < 0.001), but not with serum phosphate >5.5 mg/dL, calcium-phosphate product >55 mg(2)/dL(2), serum albumin <35 g/L, or C-reactive protein >5 mg/L. CONCLUSIONS: This uncontrolled cross-sectional study in peritoneal dialysis patients showed that sevelamer hydrochloride treatment allows an adequate serum phosphate level in about 60% of patients and significantly reduces total and LDL-cholesterol levels. Since this treatment is associated with metabolic acidosis in 22% of patients, we recommend close monitoring of bicarbonate levels in this group of patients until the clinical significance of this result is clarified. (+info)
Parathyroidectomy as a therapeutic tool for targeting the recommended NKF-K/DOQI ranges for serum calcium, phosphate and parathyroid hormone in dialysis patients.
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