Vitamin D compounds for people with chronic kidney disease requiring dialysis.

BACKGROUND: Clinical guidelines recommend vitamin D compounds to suppress serum parathyroid hormone (PTH) in chronic kidney disease (CKD), however treatment may be associated with increased serum phosphorus and calcium, which are associated with increased mortality in observational studies. Observational data also indicate vitamin D therapy may be independently associated with reduced mortality in CKD. OBJECTIVES: We assessed the effects of vitamin D compounds on clinical, biochemical, and bone outcomes in people with CKD and receiving dialysis. SEARCH STRATEGY: We searched The Cochrane Renal Group's specialised register, Cochrane's Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) in subjects with CKD and requiring dialysis that assessed treatment with vitamin D compounds. DATA COLLECTION AND ANALYSIS: Data was extracted by two authors. Results are summarised as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: Sixty studies (2773 patients) were included. No formulation, route, or schedule of administration was associated with altered risks of death, bone pain, or parathyroidectomy. Marked heterogeneity in reporting of outcomes resulted in few data available for formal meta-analysis. Compared with placebo, vitamin D compounds lowered serum PTH at the expense of increasing serum phosphorus. Trends toward increased hypercalcaemia and serum calcium did not reach statistical significance but may be clinically relevant. Newer vitamin D compounds (paricalcitol, maxacalcitol, doxercalciferol) lowered PTH compared with placebo, with increased risks of hypercalcaemia, although inadequate data were available for serum phosphorus. Intravenous vitamin D may lower PTH compared with oral treatment, and be associated with lower serum phosphorus and calcium levels, although limitations in the available studies precludes a conclusive statement of treatment efficacy. Few studies were available for intermittent versus daily and intraperitoneal versus oral administration or directly comparative studies of newer versus established vitamin D compounds. AUTHORS' CONCLUSIONS: We confirm that vitamin D compounds suppress PTH in people with CKD and requiring dialysis although treatment is associated with clinical elevations in serum phosphorus and calcium. All studies were inadequately powered to assess the effect of vitamin D on clinical outcomes and until such studies are conducted the relative importance of changes in serum PTH, phosphorus and calcium resulting from vitamin D therapy remain unknown. Observational data showing vitamin D compounds may be associated with improved survival in CKD need to be confirmed or refuted in specifically designed RCTs.

Vitamin D compounds for people with chronic kidney disease not requiring dialysis.

BACKGROUND: Vitamin D compounds are used to suppress elevated serum parathyroid hormone (PTH) in people with chronic kidney disease (CKD). OBJECTIVES: To assess the efficacy of vitamin D therapy on biochemical, bone, cardiovascular, and mortality outcomes in people with CKD and not requiring dialysis. SEARCH STRATEGY: We searched The Cochrane Renal Group's specialised register, Cochrane's Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing different forms, schedules, or routes of administration of vitamin D compounds for people with CKD not requiring dialysis were included. Vitamin D compounds were defined as established (calcitriol, alfacalcidol, 24,25(OH)(2)vitamin D(3)) or newer (doxercalciferol, maxacalcitol, paricalcitol, falecalcitriol) vitamin D compounds. DATA COLLECTION AND ANALYSIS: Data were extracted by two authors. Statistical analyses were performed using the random effects model. Results were summarized as risk ratio (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Sixteen studies (894 patients) were included. No formulation, route, or schedule of vitamin D compound was found to alter the mortality risk or need for dialysis. Vitamin D compounds significantly lowered serum PTH (4 studies, 153 patients: MD -49.34 pg/mL, 95% CI -85.70 to -12.97 (-5.6 pmol/L, 95% CI -9.77 to -1.48)) and were more likely to reduce serum PTH > 30% from baseline value (264 patients: RR 7.87, 95% CI 4.87 to 12.73). Vitamin D treatment was associated with increased end of treatment serum phosphorus (3 studies, 140 patients: MD 0.37 mg/dL, 95% CI 0.09, 0.66 (0.12 mmol/L, 95% CI 0.03, 0.21)) and serum calcium (5 studies, 184 patients: MD 0.20 mg/dL, 95% CI 0.17 to 0.23 (0.05 mmol/L, 95% CI 0.04 to 0.06)). Few data were available comparing intermittent with daily vitamin D administration, or other schedules of dosing. AUTHORS' CONCLUSIONS: There are not sufficient data to determine the effect of vitamin D compounds on mortality and cardiovascular outcomes in people with CKD not requiring dialysis. While vitamin D compounds reduce serum PTH (49.3 pg/mL (5.6 pmol/L)) compared with placebo, the relative clinical benefits of PTH lowering versus treatment-related increases in serum phosphorus and calcium remain to be understood.

Dimethylglycine supplementation does not affect plasma homocysteine concentrations in pre-dialysis chronic renal failure patients.

OBJECTIVE: To determine whether daily dimethylglycine supplementation affects plasma homocysteine concentrations. DESIGN AND METHODS: A randomized, blinded, crossover design was used. Seven pre-dialysis chronic renal failure patients consumed 400 mg of dimethylglycine or placebo daily for 28 days. Fasting blood samples and 12-h urine samples were collected at baseline and at the end of each treatment period for analysis. RESULTS: No significant differences were observed in plasma homocysteine (P = 0.624), glycine betaine (P = 0.452) and methionine (P = 0.457) concentrations between dimethylglycine and placebo treatments. CONCLUSION: Daily supplementation with dimethylglycine does not affect plasma homocysteine.

Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure.

BACKGROUND: Fasting and post-methionine load hyperhomocysteinemia are independent risk factors for vascular disease that are common in chronic renal failure. Folate decreases but seldom normalizes fasting total homocysteine (tHcy) concentrations in such patients. Glycine betaine (GB) is known to decrease tHcy in other clinical settings, but whether it is beneficial in chronic renal failure has not been established. METHODS: We conducted a crossover-controlled trial in 36 patients with chronic renal failure to determine if oral GB decreased fasting or post-methionine tHcy concentrations. All subjects received, in randomized sequence, 5-mg folic acid and 50-mg pyridoxine daily, with or without GB 4-g daily, for three months each. Fasting plasma tHcy, GB, folate, B vitamins, serum lipids and creatinine were measured at one and three months, and methionine load tests were performed at the end of each three-month treatment phase. RESULTS: GB and N,N-dimethylglycine (DMG) levels in plasma and urine increased markedly during GB treatment. Fasting tHcy decreased from baseline with both treatments but did not differ between treatments. Post-methionine tHcy decreased with both treatments and was 18% lower on GB than on folate and pyridoxine alone (P < 0.001). There were small increases in lipids during treatment with GB but the ratio of total: HDL cholesterol was unchanged. CONCLUSIONS: GB supplementation had no effect on fasting tHcy in patients with chronic renal failure who were folate and pyridoxine replete, but it significantly decreased tHcy concentrations after methionine loading.