# Markers of Mineral Metabolism in Children With CKD Stages 2 to 5D

## TL;DR

This study identifies early markers of kidney and bone disorder in children with chronic kidney disease, showing changes begin as early as stage 2.

## Contribution

The study is the first to analyze age- and sex-related CKD-MBD markers across CKD stages 2 to 5D in children.

## Key findings

- Elevated sclerostin, FGF23, and alkaline phosphatase are early markers of CKD-MBD in children with stage 2 CKD.
- PTH and iFGF23 levels rise exponentially with more severe CKD stages, while sKlotho levels decrease.
- Hyperphosphatemia and hypocalcemia only appear in CKD stages 4 to 5D, not earlier stages.

## Abstract

Changes in age- and sex-related markers for chronic kidney disease (CKD)–mineral and bone disorder (MBD) (CKD-MBD) across CKD stages 2 to 5D have not yet been studied in children.

In this cross-sectional study, we investigated age, and where applicable, sex-related z-scores of 10 key markers for CKD-MBD in 170 children with stages 2-5D.

We identified distinct CKD stage-dependent changes in CKD-MBD markers. In CKD stage 2, elevated serum sclerostin (z-score: 0.97), total fibroblast growth factor 23 (FGF23) (z-score: 0.72) and alkaline phosphatase (AP) (z-score: 0.61) concentrations were observed in association with reduced serum phosphate (z-score: −0.62) and 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) (z-score: −0.80) and a high prevalence of vitamin D deficiency or insufficiency (80.3%). From CKD stage 3A onward, increasingly elevated levels of intact FGF23 (iFGF23) (z-score: 0.49), and parathyroid hormone (PTH) (z-score: 1.68) were observed, as well as reduced levels of soluble Klotho (sKlotho) (z-score: −0.66). In contrast, hyperphosphatemia and hypocalcemia were only noted in patients with CKD stages 4 to 5D. CKD-MBD markers were highly associated with each other, with sclerostin being associated with total FGF23 and estimated glomerular filtration rate (eGFR). Total FGF23 was associated with serum phosphate, 25-hydroxyvitamin D3 (25(OH)D), transferrin saturation, and iFGF23.

Elevated sclerostin, total FGF23, and AP concentrations in combination with reduced serum phosphate and (1,25(OH)2D3) as well as vitamin deficiency or insufficiency were the earliest marker for CKD-MBD in this pediatric population and were present in CKD stage 2. This preceded the parallel exponential increase in PTH and iFGF23 and reduced sKlotho with more severe CKD in children.