Normal 25-Hydroxyvitamin D Levels Are Associated with Less Proteinuria and Attenuate Renal Failure Progression in Children with CKD

J Am Soc Nephrol. 2016 Jan;27(1):314-22. doi: 10.1681/ASN.2014090947. Epub 2015 Jun 11.


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 m(2)), serum 25-hydroxyvitamin D (25(OH)D), FGF-23, and Klotho levels were measured at baseline and after a median 8 months on ACEi. Children with 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 diastolic BP (P=0.004). ACEi therapy also associated with increased Klotho 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 survival was 75% in patients with baseline 25(OH)D ≥50 nmol/L and 50% in those with 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)D ≥50 nmol/L was associated with greater preservation of renal function. This effect was present but attenuated with concomitant ACEi therapy.

Keywords: ACE inhibitors; children; chronic kidney disease; glomerular filtration rate; proteinuria; vitamin D.

MeSH terms

  • Adolescent
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Child
  • Disease Progression
  • Female
  • Fibroblast Growth Factor-23
  • Humans
  • Male
  • Proteinuria / blood*
  • Proteinuria / complications
  • Reference Values
  • Renal Insufficiency / etiology
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy*
  • Retrospective Studies
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Angiotensin-Converting Enzyme Inhibitors
  • FGF23 protein, human
  • Vitamin D
  • Fibroblast Growth Factor-23
  • 25-hydroxyvitamin D