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

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

Rukshana Shroff  1 , Helen Aitkenhead  2 , Nikola Costa  2 , Antonella Trivelli  3 , Mieczyslaw Litwin  4 , Stefano Picca  5 , Ali Anarat  6 , Peter Sallay  7 , Fatih Ozaltin  8 , Aleksandra Zurowska  9 , Augustina Jankauskiene  10 , Giovanni Montini  11 , Marina Charbit  12 , Franz Schaefer  13 , Elke Wühl  13 ; ESCAPE Trial Group
Collaborators, Affiliations

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

Rukshana Shroff et al. J Am Soc Nephrol. 2016 Jan.

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 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.

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Figures

Figure 1.
Figure 1.
Correlation between 24-hour urinary PCR and serum 25(OH)D levels. (A) Baseline. (B) Follow-up. To convert mg/mg to mg/mmol, multiply by 113.
Figure 2.
Figure 2.
Diastolic BP is inversely associated with serum 25(OH)D at baseline. Expressed in three ranges of 25-(OH)D levels (<50, 50–75, >75 nmol/L).
Figure 3.
Figure 3.
Annualized change in eGFR expressed across three ranges of 25(OH)D levels (<50, 50–75, >75 nmol/L) in patients with CAKUT (n=129).
Figure 4.
Figure 4.
25(OH)D levels predict 5-year renal survival. (A) Baseline. (B) Follow-up. (C) Mean 25(OH)D levels predict renal survival.
Figure 5.
Figure 5.
(A) Serum FGF-23 levels at baseline and after ACEi treatment. (B) Soluble-Klotho levels at baseline and after ACEi treatment.
See this image and copyright information in PMC

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