Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial.

BACKGROUND: Memory T-cells are mediators of transplant injury, and no therapy is known to prevent the development of cross-reactive memory alloimmunity. Activated vitamin D is immunomodulatory, and vitamin D deficiency, common in hemodialysis patients awaiting transplantation, is associated with a heightened alloimmune response. Thus, we tested the hypothesis that vitamin D3 supplementation would prevent alloreactive T-cell memory formation in vitamin D-deficient hemodialysis patients. METHODS AND FINDINGS: We performed a 12-month single-center pilot randomized, controlled trial of 50,000 IU/week of cholecalciferol (D3) versus no supplementation in 96 hemodialysis patients with serum 25(OH)D<25 ng/mL, measuring effects on serum 25(OH)D and phenotypic and functional properties of T-cells. Participants were randomized 2:1 to active treatment versus control. D3 supplementation increased serum 25(OH)D at 6 weeks (13.5 [11.2] ng/mL to 42.5 [18.5] ng/mL, p<0.001) and for the duration of the study. No episodes of sustained hypercalcemia occurred in either group. Results of IFNγ ELISPOT-based panel of reactive T-cell assays (PRT), quantifying alloreactive memory, demonstrated greater increases in the controls over 1 year compared to the treatment group (delta PRT in treatment 104.8+/-330.8 vs 252.9+/-431.3 in control), but these changes in PRT between groups did not reach statistical significance (p = 0.25). CONCLUSIONS: D3 supplements are safe, effective at treating vitamin D deficiency, and may prevent time-dependent increases in T-cell alloimmunity in hemodialysis patients, but their effects on alloimmunity need to be confirmed in larger studies. These findings support the routine supplementation of vitamin D-deficient transplant candidates on hemodialysis and highlight the need for large-scale prospective studies of vitamin D supplementation in transplant candidates and recipients. TRIAL REGISTRATION: Clinicaltrials.gov NCT01175798.

Low Dietary Intake of Vitamin D and Vitamin D Deficiency in Hemodialysis Patients.

BACKGROUND: The purpose of this study was to test the hypothesis that decreased dietary intake of Vitamin D contributes to Vitamin D deficiency in end-stage renal disease (ESRD) patients on hemodialysis (HD). METHODS: We performed a cross-sectional study of 58 hemodialysis outpatients from two Mount Sinai Medical Center (MSMC)-affiliated outpatient HD units in New York City and 648 outpatients at MSMC with CKD stages I-IV. Serum 25(OH)D concentrations were measured from August 2010 to July of 2011 in recruited hemodialysis patients (n=58) and linked with results of dietary and lifestyle surveys. The Mount Sinai Data Warehouse (electronic medical record) was used to capture 25(OH) Vitamin D levels for outpatients with CKD stages I-IV who had Vitamin D testing during the same time period. RESULTS: The prevalence of Vitamin D insufficiency/deficiency in the HD cohort was 96.6%. Mean (SD) and median (IQR) 25(OH)D concentrations were 15.65 (6.82) and 13.55 (10.15) ng/mL, respectively. Dietary surveys showed a median weekly Vitamin D intake of 1044 IU (IQR=808, vs. a recommended weekly allowance of 4200 IU) and specific avoidance of foods containing both Vitamin D and phosphorus. In contrast, mean and median 25(OH)D concentrations in patients with CKD stages I-IV were 25.66 (13.44) and 23.60 (15.48) ng/mL (p<0.001 vs. HD patients). CONCLUSIONS: Vitamin D deficiency is more prevalent in HD patients than in pre-dialysis patients with CKD and is associated with decreased dietary intake of Vitamin D. Dialysis restrictions imposed to reduce dietary phosphorus intake likely contributes to the development of hypovitaminosis D in ESRD patients.

CKD classification based on estimated GFR over three years and subsequent cardiac and mortality outcomes: a cohort study.

BACKGROUND: It is unknown whether defining chronic kidney disease (CKD) based on one versus two estimated glomerular filtration rate (eGFR) assessments changes the prognostic importance of reduced eGFR in a community-based population. METHODS: Participants in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study were classified into 4 groups based on two eGFR assessments separated by 35.3 +/- 2.5 months: sustained eGFR < 60 mL/min per 1.73 m(2) (1 mL/sec per 1.73 m(2)); eGFR increase (change from below to above 60); eGFR decline (change from above to below 60); and eGFR persistently >or=60. Outcomes assessed in stratified multivariable Cox models included cardiac events and a composite of cardiac events, stroke, and mortality. RESULTS: There were 891 (4.9%) participants with sustained eGFR < 60, 278 (1.5%) with eGFR increase, 972 (5.4%) with eGFR decline, and 15,925 (88.2%) with sustained eGFR > 60. Participants with eGFR sustained < 60 were at highest risk of cardiac and composite events [HR = 1.38 (1.15, 1.65) and 1.58 (1.41, 1.77)], respectively, followed by eGFR decline [HR = 1.20 (1.00, 1.45) and 1.32 (1.17, 1.49)]. Individuals with eGFR increase trended toward increased cardiac risk [HR = 1.25 (0.88, 1.77)] and did not significantly differ from eGFR decline for any outcome. Results were similar when estimating GFR with the CKD-EPI equation. CONCLUSION: Individuals with persistently reduced eGFR are at highest risk of cardiovascular outcomes and mortality, while individuals with an eGFR < 60 mL/min per 1.73 m(2) at any time are at intermediate risk. Use of even a single measurement of eGFR to classify CKD in a community population appears to have prognostic value.