2/11/2019 4:57:17 PM

Vitamin D increases fibroblast growth factor 23 in children with advanced CKD

In children with mild to moderate chronic kidney disease, vitamin D supplementation normalized Klotho and sclerostin, according to a study published in Nephrology Dialysis Transplantation. However, the supplements increased fibroblast growth factor 23 in children with advanced CKD.

“Vitamin D deficiency is widely prevalent in children with chronic kidney disease (CKD) and contributes to mineral and bone disorder (MBD),” the authors wrote. “Normal 25-hydroxyvitamin D [25(OJ)D] levels may also reduce proteinuria and attenuate renal failure progression in children with CKD.”

To determine the effects of vitamin D supplementation in children with CKD, researchers selected 80 vitamin D-deficient children for this post-hoc analysis. Investigators studied the effects of vitamin D supplementation on fibroblast growth factor 23 (FGF23), bone alkaline phosphate (BAP), Klotho and sclerostin levels. Half of the patients included were from the randomized trial of ergocalciferol supplementation (ERGO) study and the rest from the Cardiovascular comorbidity in Children with Chronic Kidney Disease (4C) study. In each study, 20 matched children did not receive vitamin D supplementation and served as controls.

Researchers found that in patients with mild to moderate CKD in the ERGO cohort, vitamin D supplementation had no effect on FGF23 or BAP, but normalized Klotho and increased sclerostin levels. Final sclerostin however, did not differ from normal, healthy levels.

In children with advanced CDK in the 4C cohort, vitamin D supplementation increased FGF23 levels, but serum Klotho, BAP and sclerostin remained unaffected.

“This is the first report on the effects of vitamin D supplementation on markers of bone and mineral metabolism beyond PTH in children with CKD,” the authors wrote. “As expected, serum FGF23 was largely in the normal range in the ERGO cohort, but was elevated nine-fold in C4 patients, whose eGFR averaged 24 mL/min/1.73 m2.”

Researchers concluded that the consequences of increased FGF23 levels in patients with advanced CKD receiving vitamin D supplements should be addressed in future interventional trials.

“This observation is at odds with two studies in adult CKD and hemodialysis patients that failed to show a significant increase in circulating Klotho with vitamin D,” the authors wrote. This discrepancy may be at least partly due to an already diminished renal capacity for Klotho synthesis in patients with advanced CKD.” – by Scott Buzby