Antiproteinuric Treatment Reduces Urinary Excretion of Vitamin D-binding Protein in Patients with Chronic Kidney Disease

ANTIPROTEINURIC TREATMENT REDUCES URINARY EXCRETION OF VITAMIN D-BINDING PROTEIN IN PATIENTS WITH CHRONIC KIDNEY DISEASE Background: Vitamin D deficiency is associated with bone diseases but also with increased cardiovascular morbidity and mortality, and progression of renal disease. Vitamin D deficiency is found more frequently in renal disease patients than in the general population. In the circulation vitamin D is bound to vitamin D binding protein (VDBP). Previous studies indicated that nephrotic patients are vitamin D deficient probably due to urinary loss of VDBP, as tubular cells are no longer able to reabsorb VDBP. We hypothesised that antiproteinuric intervention, either by inhibition of the renin-angiotensin-aldosterone system (RAAS) or RAAS-unrelated antiproteinuric treatment, improves vitamin D status by reduction of urinary loss of VDBP. Methods: Urinary and plasma VDBP concentrations were measured in a randomized case-control cross-over study, in which patients with stable proteinuria received either ACE inhibition (ACEi) or an NSAID as antiproteinuric intervention, with preceding washout periods in which no antiproteinuric treatment was given. We also studied another randomized case-control cohort containing patients with more severe proteinuria, who were subsequently treated with either single RAAS blockade under high sodium diet (sRB/HS), or dual RAAS blockade under low sodium diet (dRB/LS). Healthy subjects screened for kidney donation were studied as controls. VDBP concentration was measured by enzyme-linked immunosorbent assay (ELISA). In a subgroup, plasma 25-hydroxyvitamin D levels were determined by radio-immuno assay (RIA). Statistical differences among groups were assessed using the Wilcoxon or Mann-Whitney non-parametric test. Data are indicated as median (range). Results: ACEi or NSAID reduced proteinuria compared to no antiproteinuric treatment, from 3.3 (1.6-13.1) to 1.5 (0.2-6.6) g/24h, and from 2.7 (1.3-12.1) to 1.2 (0.3-12.5) g/24h, respectively. Urinary VDBP decreased from 7051 (155-211027) to 2300 (5-35800) g/24h, and from 4848 (155-154510) to 1653 (97-129854), respectively. In the other cohort, proteinuria was reduced from 3.9 (1.7-7.5) (sRB/HS) to 2.4 (0.2-4.8) g/24h, respectively. Urinary VDBP was reduced from 23725 (2836-63401) to 5123 (264-16015) g/24h, respectively. Plasma VDBP levels were not affected by antiproteinuric treatment, nor were plasma 25(OH) vitamin D levels. Across all proteinuric patients, urinary VDBP correlated with proteinuria (Spearman's ρ=0.728, p