SummaryBackground and objectives Observational studies suggest that calciferol supplementation may improve laboratory and patient-level outcomes of hemodialysis patients with reduced 25-hydroxyvitamin D [25(OH)D] levels. This randomized controlled trial examined effects of cholecalciferol supplementation in patients on hemodialysis.Design, setting, participants, & measurements Sixty patients with 25(OH)D levels #24 ng/ml (#60 nmol/L) were randomized to receive 50,000 IU oral cholecalciferol or placebo, once weekly for 8 weeks and then monthly for 4 months. At baseline (autumn 2011) and 6 months, testing evaluated muscle strength, functional capacity, laboratory parameters, pulse wave velocity (PWV), and health-related quality of life (HRQOL) using the Kidney Disease Quality of Life-36 survey.Results Patients were well matched by treatment allocation. Median age was 62 years (range, 20-86), 52% were women, 55% had a history of diabetes, and mean serum 25(OH)D was 1765 ng/ml (43613 nmol/L). Patients were assessed over 6 months by repeated-measures ANOVA. Patients allocated to cholecalciferol had significantly higher values of 25(OH)D (P,0.001), 1,25-dihydroxyvitamin D (P=0.04), and tartrate-resistant acid phosphatase-5b) (P=0.04) and a greater reduction in phosphorus values (P=0.03) than placebo-treated patients Values of serum calcium, intact parathyroid hormone, and episodes of hypercalcemia and hyperphosphatemia did not differ significantly between the groups. No significant differences were detected in muscle strength, functional capacity, PWV, or HRQOL.Conclusions In this randomized controlled trial, patients supplemented with cholecalciferol had higher 25(OH)D, 1,25-dihydroxyvitamin D, and tartrate-resistant acid phosphatase-5b levels, without increased calcium or phosphorus values. However, no effects were detected in muscle strength, functional capacity, PWV, or HRQOL.

Younger, fitter patients are more vulnerable to effects of their illness on social, emotional and physical interactions and may benefit from targeted support.

SUMMARY:Treatment of chronic kidney disease (CKD) may be life-saving, but can disrupt every aspect of a patient's life and the lives of family members. Many patients with CKD are elderly with significant comorbidities and sometimes therapies to improve survival may be less important than those that improve or maintain quality of life. In this setting, patient-level benefits become particularly important goals of therapy. Randomized controlled trials (RCT) are also essential to justify expensive therapies, such as medications used in the treatment of CKD mineral and bone disorders. Surprisingly, data to support the efficacy of these drugs for patient-level outcomes remains limited. In fact, fewer RCT are conducted in renal medicine than in any other medical specialty and reliance is often placed on association data and the assessment of intermediate and biochemical end-points. While some of these may prove to be valid surrogates for clinically important outcomes, some may not. Inclusion of patient-level outcomes in clinical research provides a missing link that can inform a more comprehensive approach to clinical practice and patient care. Incorporating measures of health-related quality of life into clinical trials can make outcomes more relevant and may be relatively simple. This paper provides examples of reliable, validated instruments to measure health-related quality of life domains and functional status, together with practical instructions for their use. Most could be incorporated into RCT of CKD mineral and bone disorder treatments. Inclusion of outcomes that are perceived by patients to be significant should become standard practice in renal medicine and in clinical renal research.KEY WORDS: functional domains, health-related quality of life, patient-level outcomes, testing instruments.