Normal 25-Hydroxyvitamin D Levels Are Associated with Less Proteinuria and Attenuate Renal Failure Progression in Children with CKD
Abstract
Angiotensin-converting enzyme inhibitors (ACEi) for renin-angiotensin-aldosterone system (RAAS) blockade are routinely used to slow CKD progression. However, Vitamin D may also promote renoprotection by suppressing renin transcription through cross-talk between RAAS and Vitamin D -fibroblast growth factor-23 (FGF-23)-Klotho pathways.
To determine whether Vitamin D levels influence proteinuria and CKD progression in children, we performed a post hoc analysis of the Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of CKD in Pediatric Patients (ESCAPE) cohort. In 167 children (median EGFR 51 ml/min per 1.73 m2), serum 25-hydroxyvitaminD(25(OH)D),FGF-23, andKlotho levelsweremeasuredatbaselineandafteramedian8months onACEi.Childrenwith lower 25(OH)D levels had higher urinary protein/creatinine ratios at baseline (P=0.03) and at follow-up (P=0.006).
Levels of 25(OH)D and serum Vitamin D -binding protein were not associated, but 25(OH)D #50 nmol/L associated with higher diastolicBP(P=0.004).ACEi therapy alsoassociatedwith increasedKlotho levels (P<0.001). The annualized loss of EGFR was inversely associated with baseline 25(OH)D level (P<0.001, r=0.32).
Five-year renal survivalwas 75%in patientswith baseline 25(OH)D$50 nmol/L and 50%in thosewith lower 25(OH) D levels (P<0.001). This renoprotective effect remained significant but attenuated with ACEi therapy (P=0.05).
Renal survival increased 8.2% per 10 nmol/L increase in 25(OH)D (P=0.03), independent of EGFR; proteinuria, BP, and FGF-23 levels; and underlying renal diagnosis. In children with CKD, 25(OH)DGREATER-THAN OR EQUAL TO50 nmol/L was associatedwith greater preservation of renal function.
This effect was present but attenuated with concomitant ACEi therapy. (C) 2016 by the American Society of Nephrology.