Serum and urinary golgi membrane protein 1 (GOLM1/GP73/G73) for chronic kidney disease staging

In this cross-sectional observational study, we evaluated whether serum and urinary Golgi membrane protein 1 (GOLM1/GP73) could serve as biomarkers for CKD. Chronic kidney disease (CKD) lacks simple biomarkers reflecting both systemic burden and tubular health. GP73 is stress-responsive, but its utility across CKD and acute kidney injury (AKI) has not been systematically evaluated.

We enrolled 32 healthy individuals and 172 kidney disease patients: CKD stages 1-3 (n = 70), 4-5 (n = 42), dialysis-dependent stage 5D (n = 40), and AKI or acute-on-chronic kidney disease (n = 20). Serum G73, urinary G73, urinary creatinine, and conventional renal markers were measured. Logistic regression, AUC, decision curve analysis (DCA), and ordinal regression were used. Kidney biopsies (n = 20) were immunostained for GP73.

Serum G73 progressively increased from healthy controls to CKD stages 4-5, with a modest decrease in CKD stage 5D (median: healthy 47.2, CKD1-3 62.2, CKD4-5 96.1, CKD5D 89.9 ng/mL; P < 0.001), whereas urinary G73 and the urine G73-to-creatinine ratio progressively declined (both P < 0.001). Adding serum G73 to a clinical model (age, sex, BMI, hypertension, diabetes, CKD duration) significantly improved discrimination of advanced CKD (CKD4-5/5D vs. 1-3): AUC increased from 0.81 to 0.85 (DeLong P = 0.026), with net DCA benefit across 0-85% thresholds. Adding serum G73 to a non-renal clinical covariate model improved discrimination for advanced CKD; however, sensitivity analyses showed no meaningful incremental value beyond eGFR or serum creatinine for this eGFR-defined endpoint. Serum G73 alone showed modest ability to distinguish AKI/AonC from CKD (AUC 0.59-0.75). Kidney GP73 immunostaining was weak and unchanged across stages.

Serum G73 independently associates with CKD severity and adds diagnostic value to conventional models, especially for advanced CKD. The contrasting decline in urinary G73 and lack of increased renal tissue expression are consistent with a predominantly extra-renal contribution to circulating G73, while urinary G73 reflects tubular function. Serum and urinary G73 are useful non-invasive biomarkers that could improve CKD staging.