Serum sclerostin in biopsy-proven glomerulonephritis primarily reflects kidney function: a cross-sectional case-control study.

BACKGROUND

Sclerostin, an osteocyte-derived Wnt/β-catenin inhibitor, increases with declining kidney function and is implicated in chronic kidney disease-mineral and bone disorder (CKD-MBD). Whether circulating sclerostin reflects disease-specific activity in biopsy-proven glomerulonephritis (GN), independent of renal function and demographic confounders, remains unclear.

METHODS

In a single-centre cross-sectional case-control study, 49 adults with biopsy-proven GN and 30 healthy controls were enrolled. Serum sclerostin was measured by enzyme-linked immunosorbent assay (ELISA). Its associations with kidney function (estimated glomerular filtration rate, eGFR), proteinuria and routine biochemical parameters were examined using non-parametric tests and multivariable linear regression adjusted for age, sex and eGFR. To address baseline differences between groups and to test whether kidney function explained the observed associations, we additionally performed a propensity-score-weighted sensitivity analysis and a mediation-style statistical decomposition, with correction for multiple comparisons.

RESULTS

GN patients were older, more often male and had lower eGFR than controls. Serum sclerostin was higher in GN patients than in controls in the unadjusted comparison (median 10.86 vs 7.14 ng/mL, p < 0.001). However, this difference progressively weakened after accounting for age and sex, and was no longer statistically significant once kidney function (eGFR) was taken into account. The propensity-score-weighted sensitivity analysis showed the same pattern. Within the GN group, higher sclerostin was strongly associated with lower kidney function, and this relationship persisted in adjusted models. The apparent link between sclerostin and proteinuria was likewise explained mainly by kidney function: about three-quarters of the crude association was accounted for by the eGFR pathway (indirect effect 0.71; 95% confidence interval [95% CI] 0.16 to 1.54). Sclerostin was not robustly associated with the inflammatory markers C-reactive protein or ferritin, and an isolated inverse association with fibrinogen was regarded as exploratory because fibrinogen was measured in only 13 patients.

CONCLUSIONS

In biopsy-proven GN, elevated circulating sclerostin primarily reflects differences in kidney function, age and sex rather than GN-specific activity; within the limits of a healthy-control rather than CKD-control comparison, the data do not support serum sclerostin as an independent biomarker of glomerular disease activity. Prospective studies with non-GN CKD comparators and a complete CKD-MBD panel are needed.