BACKGROUND AND OBJECTIVES: Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification (CAC) that may contribute to high mortality of dialysis patients. CAC has been found in patients in early stages of nondialysis-dependent CKD. In this population, no study has evaluated the potential role of phosphorus binders on mortality. This study aimed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients randomized to different phosphate binders; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a randomized, multicenter, nonblinded pilot study. Consecutive outpatients (n=212; stage 3-4 CKD) were randomized to either sevelamer (n=107) or calcium carbonate (n=105). Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3-4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD. The CAC score was assessed by computed tomography at study entry and after 6, 12, 18, and 24 months. All-cause mortality, dialysis inception, and the composite end point were recorded for up to 36 months.
RESULTS: In patients randomized to sevelamer, all-cause mortality and the composite end point were lower; a nonsignificant trend was noted for dialysis inception.
CONCLUSIONS: Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception. Larger studies are needed to confirm these results.
Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.
BACKGROUND: Some trials have indicated that coronary artery calcification progresses more slowly in sevelamer-treated dialysis patients than in those using calcium-based binders. Effects of phosphate binders on circulating advanced glycation end products (AGEs) are unknown.
STUDY DESIGN: Randomized trial with parallel-group design.
SETTING & PARTICIPANTS: 183 adult (aged >20 years) patients on maintenance hemodialysis therapy at 12 dialysis facilities with a mean vintage of 118 ± 89 (median, 108) months. Dialysate calcium concentration was 2.5 mEq/L, and dietary calcium was not controlled.
INTERVENTION: Patients were randomly assigned to 12 months of treatment with sevelamer (n = 91) or calcium carbonate (n = 92).
OUTCOMES & MEASUREMENTS: Primary outcome measures were change from baseline in coronary artery calcification score (CACS) determined at study entry and completion using multislice computed tomography and the proportion of patients with a ≥ 15% increase in CACS. Blood parameters were determined at study entry and 2-week intervals, and levels of plasma pentosidine, a representative AGE, were determined at study entry, 6 months, and study completion.
RESULTS: 79 (86.8%) and 84 (91.3%) patients in the sevelamer and calcium-carbonate arms completed the treatment, respectively. Both binders were associated with an increase in mean CACS: 81.8 (95% CI, 42.9-120.6) and 194.0 (139.7-248.4), respectively (P < 0.001 for both). After adjustment for baseline values, the increase in the sevelamer group was 112.3 (45.8-178) less (P < 0.001). Percentages of patients with a ≥ 15% increase in CACS were 35% of the sevelamer group and 59% of the calcium-carbonate group (P = 0.002). Plasma pentosidine levels increased with calcium carbonate but not [corrected] sevelamer treatment (P < 0.001). Sevelamer use was associated with decreased risk of a ≥ 15% increase in CACS regardless of baseline blood parameters, pentosidine level, and CACS.
LIMITATIONS: Treatment duration was relatively short, some sevelamer-treated patients (7 of 79) received calcium carbonate, and washout could not be performed.
CONCLUSIONS: The data suggest that sevelamer treatment slowed the increase in CACS and suppressed AGE accumulation.
A favorable survival effect of phosphate binders (PBs) on incident hemodialysis (HD) patients was recently reported, but no definitive advantages of calcium-based or noncalcium-based PBs have been demonstrated. The aim of this study was to assess the impact of the prescription of PBs using calcium carbonate (CaCO3) or sevelamer HCl (SV) on survival. Baseline PB prescription was recorded using a cross-sectional analysis of prevalent HD patients from the regional Association Régionale des Néphrologues OStéodystrophie French cohort. A prospective 42-month survival analysis study was performed. In July 2005, 1347 HD patients were included. CaCO3, SV, and mixed PBs were prescribed in 55%, 42%, and 24% of cases, respectively, and 26% were not prescribed PBs. Using a Cox proportional model adjusted for several parameters, CaCO3 use was found to be associated with less mortality (HR, 0.64 [0.4–0.78]), but not in the case of SV use (HR, 1.13 [0.92–1.3]). SV prescription was associated with higher mortality than CaCO3 (HR, 1.46 [1.1–1.9]). CaCO3, but not sevelamer prescription, is associated with a favorable effect on survival in a French HD population. This novel result can be partly accounted for by the differences in mineral metabolism disorder management that exist between randomized controlled trials and “real life” conditions.
BACKGROUND: Vascular calcification (VC) contributes to cardiovascular disease in haemodialysis (HD) patients. Few controlled studies have addressed interventions to reduce VC but non-calcium-based phosphate binders may be beneficial. No published randomized study to date has assessed the effect of lanthanum carbonate (LC) on VC progression.
METHODS: We conducted a pilot randomized controlled trial to determine the effect of LC on VC. Forty-five HD patients were randomized to either LC or calcium carbonate (CC). Primary outcome was change in aortic VC after 18 months. Secondary outcomes included superficial femoral artery (SFA) VC, bone mineral density (BMD) of lumbar spine and serum markers of mineral metabolism. At baseline, 6 and 18 month computed tomography was performed to measure VC and BMD. A random effect linear regression model was performed to assess differences.
RESULTS: Thirty patients completed the study (17 LC, 13 CC); baseline median age 58 years, 38% diabetic, 64% male. Ninety-three per cent had aortic VC at commencement and 87% showed progression. At 18 months, there was significantly less aortic VC progression with LC than CC (adjusted difference -98.1 (-149.4, -46.8) Hounsfield units (HU), P < 0.001). There was also a non-significant reduction with LC in left SFA VC (-25.8 (-67.7, 16.1) HU, P = 0.2) and right SFA VC (-35.9 (-77.8, 5.9) HU, P = 0.09). There was no difference in lumbar spine BMD and serum phosphate, calcium and parathyroid hormone levels between groups. Limitations to the study include small sample size and loss to follow up.
CONCLUSIONS: Lanthanum carbonate was associated with reduced progression of aortic calcification compared with CC in HD patients over 18 months.
BACKGROUND: Despite substantial progress in medical care, the mortality rate remains unacceptably high in dialysis patients. Evidence suggests that bone mineral dismetabolism (CKD-MBD) might contribute to this burden of death. However, to date only a few papers have investigated the clinical relevance of serum mineral derangements and the impact of different therapeutic strategies on mortality in a homogeneous cohort of south European dialysis patients.
METHODS: The RISCAVID study was a prospective, observational study in which all patients receiving hemodialysis (HD) in the north-western region of Toscany in June 2004 were enrolled (N=757) and followed up for 24 months.
RESULTS: At study entry, only 71 (9%) patients of the entire study cohort exhibited an optimal control of serum phosphorous (Pi), calcium (Ca), calciumX-phosphorous product (CAXPi) and intact parathyroidhormone (iPTH) according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical guidelines. Despite a similar prevalence, the severity of CKD-MBD appeared different to the results reported in the USA. Interestingly, none of the serum biomarkers or number of serum biomarkers within KDOQI targets was independently associated with all-cause and cardiovascular (CV) mortality. Among treatments, Sevelamer was the only drug independently associated with lower all-cause and cardiovascular mortality (p<0.001).
CONCLUSION: The RISCAVID study highlights the difficulty of controlling bone mineral metabolism in HD patients and lends support to the hypothesis that a carefully chosen phosphate binder might impact survival in HD patients.
AIMS: In individuals with chronic kidney disease (CKD), including those undergoing maintenance hemodialysis (MHD), coronary artery calcification (CAC) is common. We hypothesized that, in MHD patients, intake of the calcium-free phosphate binder sevelamer is associated with lower CAC compared to calcium-based phosphate binders (CBPB).
MATERIAL AND METHODS: This is a cross-sectional study of MHD patients, who underwent computerized tomography to assess coronary artery calcium scores (CACS). Patients were stratified into two mutually exclusive groups based on taking only a CBPB vs. sevelamer. Logistic regression was used to calculate adjusted odds ratio (OR) of CACS > or = 400, CACS 100 < or =; CACS < 400, 10 < or =; CACS < 100 vs. CACS < 10.
RESULTS: 117 MHD patients were either on a CBPB alone (n = 60) or sevelamer alone (n = 57). Despite increased prevalence of DM in the sevelamer group (58%) as compared to the CBPB group (35%), CACS was significantly lower with sevelamer use (283 + or - 83 vs. 494 + or - 94, p = 0.02). The OR of significant CACS > or =; 400 vs. CAC < 10 was 4.35 (95% confidence interval: 1.5 - 9.9, p = 0.008) for CBPB compared with sevelamer, after controlling for case-mix, cholesterol-lowering medication, DM, and inflammatory markers.
CONCLUSION: In our cohort, significant CAC was significantly more prevalent among MHD patients taking CBPB as compared to sevelamer monotherapy.
BACKGROUND/AIM: Vascular calcification is thought to be associated with a high cardiovascular mortality rate in patients with end-stage renal disease. Control of hyperphosphataemia is important for the treatment of the vascular calcification. The aim of the present study was to evaluate the effects of sevelamer hydrochloride on the progression of aortic calcification in haemodialysis (HD) patients. METHODS: 42 HD patients were studied in this study and divided into two groups (sevelamer vs. calcium). Sevelamer was added and titrated up to achieve serum P control for 6 months. The estimations of aortic calcification index (ACI) by abdominal computed tomography scans were performed twice in each patient. We compared the changes in serum calcium, phosphorus, intact parathyroid hormone, and lipids in two groups. RESULTS: Serum phosphorus levels decreased significantly from 6.7 +/- 0.7 to 6.2 +/- 0.5 mg/dl with no changes in serum intact parathyroid hormone levels in the sevelamer group (p < 0.01), and increased from 6.5 +/- 1.0 to 6.7 +/- 1.1 mg/dl in the calcium group (p < 0.05). Serum calcium levels did not change in the sevelamer group and calcium group. The serum levels of total cholesterol decreased significantly from 158.5 +/- 20.7 to 146.2 +/- 24.1 mg/dl (p = 0.024) and the low-density lipoprotein cholesterol level from 65.3 +/- 14.4 to 54.7 +/- 11.6 mg/dl (p = 0.014) in the sevelamer group. Serum C-reactive protein decreased significantly from 0.14 +/- 0.13 to 0.08 +/- 0.11 mg/dl in the sevelamer group (p = 0.038) and significantly increased (0.18 +/- 0.09 vs. 0.22 +/- 0.12 mg/dl) in the calcium group (p = 0.042). The mean changes in ACI (DeltaACI) were 3.6 +/- 1.5% in the sevelamer group and 8.2 +/- 3.1% in the calcium group. CONCLUSIONS: Sevelamer allows a better serum phosphorus control compared with calcium-based phosphate binder and suppresses the progression of aortic calcification in HD patients.
Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification (CAC) that may contribute to high mortality of dialysis patients. CAC has been found in patients in early stages of nondialysis-dependent CKD. In this population, no study has evaluated the potential role of phosphorus binders on mortality. This study aimed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients randomized to different phosphate binders; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
This is a randomized, multicenter, nonblinded pilot study. Consecutive outpatients (n=212; stage 3-4 CKD) were randomized to either sevelamer (n=107) or calcium carbonate (n=105). Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3-4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD. The CAC score was assessed by computed tomography at study entry and after 6, 12, 18, and 24 months. All-cause mortality, dialysis inception, and the composite end point were recorded for up to 36 months.
RESULTS:
In patients randomized to sevelamer, all-cause mortality and the composite end point were lower; a nonsignificant trend was noted for dialysis inception.
CONCLUSIONS:
Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception. Larger studies are needed to confirm these results.
