Abstract
INTRODUCTION AND AIMS: Vitamin D insufficiency is highly prevalent amongst renal transplant recipients and in observational studies is associated with adverse outcomes. Hypercalcaemia, usually due to persistent hyperparathyroidism, also commonly occurs in this population and often coexists with vitamin D insufficiency. However, concern that Vitamin D supplementation might exacerbate the pre-existing hypercalcemia often leads clinicians to avoid Vitamin D supplementation in such patients. This feasibility study aimed to quantify the effect on serum calcium of short-term low dose cholecalciferol supplementation in a group of hypercalcemic renal transplant recipients. METHODS: We conducted a two-week, single arm, open-label, trial of 1000iu cholecalciferol supplementation daily in 18 hypercalcaemic, vitamin D insufficient adult patients with a functioning renal allograft (eGFR >30 30 ml/min/1.73m2). At baseline and following 2 weeks of treatment serum creatinine, eGFR, calcium, phosphorous, iPTH, albumin, 25- and 1,25-dihydroxycholecalciferol, fibroblast growth factor-23 (FGF23) and urinary calcium and creatinine were measured. Subjects were counseled to maintain their usual diet. Variables are summarized using their mean (sd) or median (Intra-Quartile Range [IQR]). Change over follow-up are examined using Wilcoxin signed ranks tests with a 2-sided type 1 error rate of 0.05. RESULTS: The mean age was 53(13) years and mean duration of transplantation was 7.6(4.8) years; 13(72%) of subjects were male. Baseline eGFR was 56(12) ml/min/1.73m2. All subjects were vitamin D insufficient (mean baseline 25-hydroxycholecalciferol level was 40.1(14.3) nmol/L); all had a baseline serum albumin >42 mmol/L and the mean (sd) serum calcium was 2.63(0.15) mmol/L. Mean (sd) iPTH was 127(72). PTH correlated with ionized calcium r=0.69, p=0.03. With supplementation the median rise in 25- and 1,25-hydroxycholecalciferol were 9.0 nmol/L, p<0.05 and 21.9 mmol/L, p=0.05 respectively. Median (IQR) change in serum calcium from baseline to follow-up was -0.02 (-0.9 to 0.02); p=0.3. Ionized calcium (n=15) decreased from 1.31(0.08) at baseline to 1.29(0.07), p= 0.05. There was a trend for an increase in serum phosphate (within the normal range) from 0.83(0.11) mmol/L to 0.88(0.16), p=0.08, without any substantial change in FGF23 (median change: -1.9). The median (IQR) change in the urinary calcium:creatinine ratio was 0.002 (-23.5 to 22.73), p=0.88). The change in ionized calcium correlated with change in 25-OH Vitamin D (r=0.64, p=0.01) but not with change in other measures. CONCLUSIONS: In hypercalcemic vitamin D insufficient renal transplant recipients low-dose short-term oral cholecalciferol supplementation improves vitamin D levels without exacerbating hypercalcaemia or increasing the urinary calcium;creatinine ratio.
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