title: 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 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.
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Rukshana.Shroff@gosh.nhs.uk.
authors.forename: Rukshana
authors.initials: R
authors.lastname: Shroff
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom;
authors.forename: Helen
authors.initials: H
authors.lastname: Aitkenhead
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom;
authors.forename: Nikola
authors.initials: N
authors.lastname: Costa
authors.affiliation: G. Gaslini Institute, Genova, Italy;
authors.forename: Antonella
authors.initials: A
authors.lastname: Trivelli
authors.affiliation: The Children's Memorial Health Institute, Warsaw, Poland;
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Litwin
authors.affiliation: Ospedale Pediatrico Bambino Gesù, Rome, Italy;
authors.forename: Stefano
authors.initials: S
authors.lastname: Picca
authors.affiliation: Cukurova University School of Medicine, Balcali, Adana, Turkey;
authors.forename: Ali
authors.initials: A
authors.lastname: Anarat
authors.affiliation: Semmelweis University Budapest, 1st Department of Pediatrics, Budapest, Hungary;
authors.forename: Peter
authors.initials: P
authors.lastname: Sallay
authors.affiliation: Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey;
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.affiliation: Department of Paediatric and Adolescent Nephrology and Hypertension, Medical University of Gdansk, Gdansk, Poland;
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Zurowska
authors.affiliation: Vilnius University Paediatric Center, Vilnius, Lithuania;
authors.forename: Augustina
authors.initials: A
authors.lastname: Jankauskiene
authors.affiliation: Unit of Pediatric Nephrology and Dialysis, Bologna, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montini
authors.affiliation: Hopital Necker, Paris, France; and.
authors.forename: Marina
authors.initials: M
authors.lastname: Charbit
authors.affiliation: Center for Pediatric & Adolescent Medicine, University of Heidelberg, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Schaefer
authors.affiliation: Center for Pediatric & Adolescent Medicine, University of Heidelberg, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Wühl
mesh_terms: D000293:Adolescent; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002648:Child; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D008297:Male; D011507:Proteinuria / Q000097:blood* / Q000150:complications; D012016:Reference Values; D051437:Renal Insufficiency / Q000209:etiology; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; C000717427:FGF23 protein, human; D014807:Vitamin D; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D
keywords: ACE inhibitors; children; chronic kidney disease; glomerular filtration rate; proteinuria; vitamin D