title: Antiproteinuric treatment reduces urinary loss of vitamin D-binding protein but does not affect vitamin D status in patients with chronic kidney disease.
abstract: 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 D(3) 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 D(3) and 1,25-dihydroxyvitamin D(3) 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 40mg QD (ACEi, 6 weeks), or indomethacin 75mg 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 D(3) levels by LC-MS and 1,25-dihydroxyvitamin D(3) levels by radioimmunoassay. In CKD patients urinary VDBP excretion was strongly increased (median (range) 5413 (155-211,027) μg/24h) as compared to healthy controls (64 (23-111) μg/24h, p<0.001). Both NSAID and ACEi significantly decreased urinary VDBP excretion, in proportion to proteinuria reduction. Plasma VDBP, 25-hydroxyvitamin D(3) and 1,25-dihydroxyvitamin D(3) 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 D(3) levels, suggesting that urinary loss of VDBP does not affect vitamin D status.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
authors.forename: Carolina R C
authors.initials: CR
authors.lastname: Doorenbos
authors.forename: Milton M
authors.initials: MM
authors.lastname: de Cuba
authors.forename: Liffert
authors.initials: L
authors.lastname: Vogt
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.forename: Jacob
authors.initials: J
authors.lastname: van den Born
authors.forename: Reinold O B
authors.initials: RO
authors.lastname: Gans
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood / Q000652:urine*; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy* / Q000652:urine; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D014809:Vitamin D-Binding Protein / Q000097:blood / Q000652:urine*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; D006887:Hydroxycholecalciferols; D007783:Lactones; D013450:Sulfones; D014809:Vitamin D-Binding Protein; C116926:rofecoxib; D017706:Lisinopril; D007213:Indomethacin