Combination Vitamin D Therapy in Stage 5 Chronic Kidney Disease

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Annals of Pharmacotherapy (Impact Factor: 2.06). 07/2011; 45(7-8):1011-5. DOI: 10.1345/aph.1P782
Source: PubMed


To review the data supporting combination therapy with vitamin D and vitamin D receptor activators (VDRAs) in patients with stage 5 chronic kidney disease (CKD).
Literature was searched using PubMed and EMBASE using the terms kidney disease, kidney failure-chronic, and vitamin D. Limits applied included humans, adults (19 years or older), and clinical trials (and related), with publication dates between January 1, 1980, and May 16, 2011.
All English-language publications were analyzed for relevance. Studies appropriate to the objective were evaluated, including 3 prospective observational studies, 1 prospective cohort study, and 1 retrospective study.
To our knowledge, there have been no randomized controlled trials evaluating the safety and efficacy of vitamin D supplementation in combination with VDRA therapy in patients with stage 5 CKD. Relatively small observational studies have demonstrated improvements in 25-hydroxyvitamin D (25-OHD) concentrations and markers of mineral and bone metabolism as well as reduced VDRA use in patients with stage 5 CKD. Not all patients in these studies were receiving VDRA therapy. Therapy was safe, with no patients exceeding the recommended upper limit for 25-OHD concentrations and only a small percentage experiencing transient/correctable hypercalcemia.
Vitamin D supplementation to maintain 25-OHD concentrations at 20-30 ng/mL or higher with or without VDRA therapy is inexpensive, appears safe, and may have additional health benefits in patients with stage 5 CKD. Well-designed, randomized controlled trials are needed to determine the efficacy and safety of combination vitamin D therapy in patients with stage 5 CKD.

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    • "Data concerning PTH reduction by the coadministration of nutritional vitamin D and VDRA are still heterogeneous and mainly acquired in observational fashion [38]. Furthermore , only a subset of patients concomitantly received the nutritional and the active vitamin D in those studies [39]. Calcifediol was associated with a significant PTH reduction and a lowering rate of alfacalcidol administration from 66% to 43% in 149 dialysis patients during 6 months of followup [40]. "
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    ABSTRACT: Vitamin D is a common treatment against secondary hyperparathyroidism in renal patients. However, the rationale for the prescription of vitamin D sterols in chronic kidney disease (CKD) is rapidly increasing due to the coexistence of growing expectancies close to unsatisfactory evidences, such as (1) the lack of randomized controlled trials (RCTs) proving the superiority of any vitamin D sterol against placebo on patients centered outcomes, (2) the scanty clinical data on head to head comparisons between the multiple vitamin D sterols currently available, (3) the absence of RCTs confirming the crescent expectations on nutritional vitamin D pleiotropic effects even in CKD patients, (4) the promising effects of vitamin D receptors activators (VDRA) against proteinuria and myocardial hypertrophy in diabetic CKD cohorts, and (5) the conflicting data on the impact on mortality of VDRA versus calcimimetic centered regimens to control CKD-MBD. The present review arguments these issues focusing on the opened questions that nephrologists should consider dealing with the prescription of nutritional vitamin D or VDRA and with the choice of a VDRA versus a calcimimetic based regimen in CKD-MBD patients.
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    ABSTRACT: To review the inter-relationships between calcium, phosphorus, parathyroid hormone (PTH), parent and activated vitamin D metabolites (vitamin D, 25(OH)-vitamin D, 1,25(OH)2 -vitamin D, 24,25(OH)2 -vitamin D), and fibroblast growth factor-23 (FGF-23) during chronic kidney disease (CKD) in dogs and cats. Human and veterinary literature. Beneficial effects of calcitriol treatment during CKD have traditionally been attributed to regulation of PTH but new perspectives emphasize direct renoprotective actions independent of PTH and calcium. It is now apparent that calcitriol exerts an important effect on renal tubular reclamation of filtered 25(OH)-vitamin D, which may be important in maintaining adequate circulating 25(OH)-vitamin D. This in turn may be vital for important pleiotropic actions in peripheral tissues through autocrine/paracrine mechanisms that impact the health of those local tissues. Limited information is available reporting the benefit of calcitriol treatment in dogs and cats with CKD. A survival benefit has been shown for dogs with CKD treated with calcitriol compared to placebo. The concentrations of circulating 25(OH)-vitamin D have recently been shown to be low in people and dogs with CKD and are related to survival in people with CKD. Combination therapy for people with CKD using both parental and activated vitamin D compounds is common in human nephrology and there is a developing emphasis using combination treatment with activated vitamin D and renin-angiotensin-aldosterone-system (RAAS) inhibitors.
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    ABSTRACT: Background Traditionally, secondary hyperparathyroidism (SHPT) due to low calcitriol synthesis in failing kidneys has been treated with synthetic vitamin D receptor (VDR) activators. Recently, also the importance of low native vitamin D status beyond the issue of SHPT has been recognized in these patients. The aim of this work was to evaluate the effect of cholecalciferol supplementation in haemodialysis patients with low vitamin D serum levels. Another aim was to evaluate dual vitamin D therapy (cholecalciferol supplementation plus paricalcitol) in haemodialysis patients with vitamin D deficiency and concomitant SHPT. Methods Ninety clinically stable maintenance haemodialysis patients were included. Supervised cholecalciferol supplementation was administered due to low vitamin D status. Patients with SHPT were also treated with synthetic VDR activator. Two pre hoc subgroups for statistical analysis were formed: patients treated solely with cholecalciferol (N = 34; 5,000 IU once weekly) and patients treated with a combination of cholecalciferol (identical dose, i.e. 5,000 IU/week) plus paricalcitol (N = 34, median dose 10 μg/week). Follow-up visit was scheduled 15 weeks later. Serum concentrations of calcidiol (25-D), parathyroid hormone (PTH) and beta-cross laps (CTX) were assessed at baseline and at follow-up. Serum calcium, phosphate and alkaline phosphatase (ALP) were monitored monthly. Only non-calcium gastrointestinal phosphate binders were administered. Dialysate calcium was 1.5 mmol/L in all patients, and no oral calcium-containing preparations were prescribed. Depending on data distribution, parametric or nonparametric statistical methods were used for comparison within each group (i.e. baseline vs. follow-up data) as well as between groups. Results In the whole group of 90 patients, mean baseline 25-D serum level was 20.3 (standard deviation 8.7) nmol/L, and it increased to 66.8 (19) nmol/L (p
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