Antiproteinuric treatment reduces urinary loss of vitamin D-binding protein but does not affect vitamin D status in patients with chronic kidney disease

Vitamin D deficiency is common in chronic kidney disease (CKD). Increased urinary loss of vitamin D binding protein (VDBP), the main transporter of 25-hydroxyvitamin D3 in the circulation, has been postulated to contribute to vitamin D deficiency in proteinuria. To test this hypothesis we analyzed urinary and plasma levels of VDBP, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 from proteinuric patients, before and after antiproteinuric interventions.We performed a post-hoc analysis of a clinical trial in CKD patients (n = 13, creatinine clearance median 60 (range 25–177) ml/min) subjected to the following study periods: washout (no antiproteinuric treatment, 4 weeks), lisinopril 40 mg QD (ACEi, 6 weeks), or indomethacin 75 mg BID (NSAID, 4 weeks) in randomized sequence. Healthy subjects screened for donation (n = 10) served as controls. Plasma and urine VDBP levels were measured by ELISA, 25-hydroxyvitamin D3 levels by LC–MS and 1,25-dihydroxyvitamin D3 levels by radioimmunoassay.In CKD patients urinary VDBP excretion was strongly increased (median (range) 5413 (155–211,027) μg/24 h) as compared to healthy controls (64 (23–111) μg/24 h, p < 0.001). Both NSAID and ACEi significantly decreased urinary VDBP excretion, in proportion to proteinuria reduction. Plasma VDBP, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels, however, were similar between patients and controls and not affected by antiproteinuric intervention.Urinary VDBP excretion is markedly increased in proteinuria and responds to antiproteinuric treatment. Urinary VDBP loss is not associated with plasma VDBP or vitamin D3 levels, suggesting that urinary loss of VDBP does not affect vitamin D status.

► Vitamin D deficiency is a common problem in chronic kidney disease (CKD). ► Proteinuria has been suggested to cause vitamin D deficiency in CKD. ► We found that anti-proteinuric treatment reduces urinary vitamin D binding protein. ► No relationship between proteinuria and vitamin D levels was found. ► Anti-proteinuric treatment did not affect vitamin D levels.