Vitamin D Supplements Not Advised in First Year Post–Kidney Transplant

Kidney transplant recipients with vitamin D deficiency who received vitamin D supplementation fared no better in the short term posttransplant than those who did not receive vitamin D. Supplementation may even have had adverse effects on the transplanted organs, a study shows.

Almost 90 percent of patients who receive renal allografts show a lack of vitamin D because of treatments with corticosteroids for immunosuppression as well as advice to avoid sun exposure because of an increased risk of cancer from immunosuppression. However, there has not been consensus about what to do for these patients.

Researchers led by Ursula Thiem, MD, of the Division of Nephrology and Dialysis at the Medical University of Vienna, Austria, conducted VITA-D, a large, randomized, placebo-controlled, double-blind trial among adult kidney transplant recipients whose calcidiol levels were less than 50 nmol/L (equivalent to 20 ng/mL). Patients (n = 203) were randomly assigned in a 1:1 ratio to receive either 6800 IU oral vitamin D3 daily or placebo for 1 year.

Outcome measures were renal function as assessed by serum creatinine, as well as the incidence of rejection episodes and infections at 1 year posttransplant. Rejection episodes and infections were weighted by severity to produce a monthly combined event rate. Analyses of only those patients who were compliant and completed the study were performed at 6 (n = 135) and 12 months (n = 123).

Thiem presented the study at the annual meeting of the European Renal Association—European Dialysis and Transplant Association conference in London in May.

Worse kidney function with vitamin D3 supplementation

At 12 months, patients who had received vitamin D3 supplements had worse allograft function than patients who had received placebo. A per protocol analysis showed that the serum creatinine level for the group taking the vitamin supplements was 1.545 mg/dL compared to 1.415 mg/dL for patients on placebo (p = 0.0157). Analysis at 6 months showed an even more dramatic difference: 1.61 mg/dL with supplementation vs. 1.43 mg/dL without (p = 0.0052). There were no differences between the groups in terms of the incidence of acute rejection episodes or infections.

The authors concluded that kidney transplant recipients’ renal function was not improved in the short term by treatment of their vitamin D deficiency, and vitamin D supplementation may have even had negative effects on allograft function.

Senior author Kyra Borchhardt, MD, of the Medical University of Vienna and the Dialysis Institute Klagenfurt in Austria commented that the vitamin D3 dosing regimen in the study achieved adequate 25-hydroxyvitamin D levels in the majority of patients at 6 and 12 months. Nonetheless, any expected benefits on allograft function were not seen. The researchers had hypothesized that fewer rejection episodes and infections could improve allograft function, but “there was no difference in the incidence of infections and acute allograft rejections between vitamin D3-treated patients and control patients,” she said.

She noted that the patients in the group receiving vitamin D3 supplements had received organs from significantly older donors, which could predispose them to worse outcomes. But once this and other possible confounding factors were controlled for, the negative treatment effect of vitamin D3 was still apparent at 6 and 12 months.

Although Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend vitamin D supplementation after kidney transplant, Borchhardt notes that KDIGO emphasizes that the recommendation is based on low-quality evidence because of a lack of randomized, controlled trials. In light of the VITA-D study results, “we believe that vitamin D therapy in the first year after kidney transplantation should be considered carefully and closely monitored for hypercalcemia.” she said.

So far, the VITA-D investigators have not performed any subgroup analyses of their data, so the possibility remains that certain subgroups of patients could benefit by taking vitamin D posttransplant, Borchhardt said.