Association of Podometric Parameters with the Oxford MEST-C Score and Pretreatment eGFR Slope in Patients with IgA...

Podocyte loss correlates with chronic Oxford lesions (S/T), and urinary podocyte mRNA links to active lesions (E/C). A lower podocyte number was the sole independent predictor of the prebiopsy eGFR slope. Quantitative podometrics may serve as a new biomarker to refine risk stratification in IgA nephropathy.

IgA nephropathy is the most prevalent primary glomerular disease worldwide; however, its heterogenous clinical course complicates prognostic prediction. Podometrics, a quantitative assessment of podocytes based on the recently proposed "podocyte depletion hypothesis," has been suggested as a potential predictor of renal outcomes in various glomerular diseases. Nevertheless, its correlation with the Oxford classification or the prebiopsy eGFR slope remains unclear. This study aimed to investigate the association between podometrics and mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), and crescent (C) scores and identify podometric parameters associated with the prebiopsy eGFR slope.

Kidney biopsy specimens from 101 patients diagnosed with immunoglobulin A nephropathy at our institution between 2019 and 2022 were evaluated using the Oxford classification and podometrics. Patients were categorized into decline and nondecline groups based on their prebiopsy eGFR slope. Urinary mRNA levels of podocyte markers (NPHS1 and NPHS2) were measured in 94 patients. Independent factors associated with the decline group were identified through multivariate nominal logistic regression analysis.

Patients with stage S1 or T1/2 exhibited significantly lower podocyte densities and numbers compared with those with stage S0 or T0, respectively. Elevated urinary podocyte marker levels were associated with E1 and C1/C2 lesions. The decline group exhibited significantly lower podocyte density and number and larger mean podocyte volume compared with the nondecline group. In the multivariate analysis, a lower podocyte number was the only independent factor associated with the decline group.

The podocyte number at the time of kidney biopsy was associated with the pre-biopsy eGFR decline slope in patients with immunoglobulin A nephropathy. Furthermore, elevated urinary podocyte mRNA levels suggested the presence of E and C lesions. Podometrics may serve as a potentially less invasive marker for monitoring disease activity and guiding treatment strategies.