Urinary Sclerostin and Renal Magnesium Handling in Proteinuric Non-Diabetic Chronic Kidney Disease

Sclerostin is involved in chronic kidney disease-mineral and bone disorder (CKD-MBD), but its relation to renal magnesium handling remains unclear. We investigated whether urinary and serum sclerostin were associated with fractional excretion of magnesium (FeMg) in proteinuric non-diabetic chronic kidney disease (CKD).

In this cross-sectional study, 70 adults with proteinuric non-diabetic CKD stage 1 to 5 at a tertiary medical center were enrolled. Urinary sclerostin normalized to urine creatinine (Uscl/Ucre) and serum sclerostin were measured. Their associations with ln-transformed FeMg [ln(FeMg)] were examined using multivariable linear regression with sequential adjustment for age, sex, estimated glomerular filtration rate (eGFR), proteinuria, electrolytes, serum sclerostin, and CKD-MBD markers including plasma intact parathyroid hormone, serum fibroblast growth factor 23, and soluble alpha-Klotho.

Urinary sclerostin (Uscl/Ucre) increased across CKD stages, and higher Uscl/Ucre tertiles were associated with higher FeMg. Uscl/Ucre was positively associated with ln(FeMg) in crude analysis (β 0.652; p < 0.001) and this association still existed after adjustment for age, sex, eGFR, serum magnesium, and CKD-MBD markers (β 0.366; p < 0.001). Compared with the lowest tertile, the highest urinary sclerostin tertile was significantly associated with higher ln(FeMg) (β 0.662; p = 0.007). In contrast, serum sclerostin was not associated with ln(FeMg) after adjustment.

In proteinuric non-diabetic chronic kidney disease, urinary but not serum sclerostin is independently associated with fractional excretion of magnesium. Urinary sclerostin may reflect intrarenal processes relevant to tubular magnesium handling.