Zinc supplementation trial in pediatric chronic kidney disease: effects on circulating FGF23 and Klotho.

Abstract

Abstract Background Zinc status and its role in bone metabolism has not been studied in children with chronic kidney disease (CKD). Methods Forty-one children (25 male and 16 female, age 12.94±4.13 years) with CKD in native or transplanted kidneys were recruited through two pediatric nephrology divisions in Ontario, Canada and their zinc status was assessed. 14 patients (64% enrolment rate) with identified zinc deficiency received zinc citrate supplement for 3 months in the dose of 10 mg orally once a day for age 4-8 years, and 10 mg twice a day for age 9-18 years. Results Zinc deficiency (plasma concentration < 11.5 µmol/L) was found in 22 patients (53.7%). A linear regression model suggested that for every 1 unit drop of eGFR zinc concentration dropped by 0.026 µmol/L (p=0.04). Zinc deficiency was associated with higher serum intact FGF-23; however, this was predominantly determined by the falling GFR. Zinc deficient and sufficient children had similar circulating cFGF-23 and alpha-Klotho. Normalization of plasma zinc concentration was achieved in 8 patients rising from 9.96±1.48 to 12.39±3.89 μmol/L (p=0.0073). In children treated with zinc but not receiving calcitriol a statistically significant (p=0.0078) rise in c-terminal FGF-23 was observed. However, no other meaningful changes to biochemical measures or an increase in phosphaturia were observed. Conclusion Zinc status is related to kidney function and connected to bone metabolism in patients with CKD. However, it plays a minor role in fine-tuning various metabolic processes and therapeutic supplementation seems to only modestly improve bone metabolism in asymptomatic CKD patients.