Clinical Impact of Podometrics and Quantitation of Podocyte Parameters in Patients with IgA Nephropathy (IgAN)

Background: Podocyte loss and resultant nephron loss are common processes in developing glomerulosclerosis and chronic kidney disease. Podometrics for estimating podocyte number, density, glomerular volume and other parameters in kidney biopsies, can be an important toolbox for monitoring glomerular disease. We validated podometrics in patients with IgAN. Methods: Biopsy-proven IgAN patients with our hospital from 2019 to 2022 were enrolled in this study (n=44, median age 35.5 years [25-57.5], 45.5% male) and podocyte parameters were measured using the technology of Venkatareddy et al. (JASN 2014). Glomerular volume, mean podocyte volume, and podocyte density were measured and divided into two groups, high and low, respectively, to determine their relationship to clinical characteristics. Podocyte parameters were compared between the groups categorized based on the presence or absence of lesion defined by Oxford MEST-C scores (mesangial hypercellularity: M, endocapillary hypercellularity: E, segmental sclerosis or adhesion: S, interstitial fibrosis and tubular atrophy: T, and crescents: C). Results: Patients with larger glomerular and podocyte volumes were older and had lower eGFR than those with smaller volumes. Patients with lower podocyte density were older, had lower eGFR, and higher UP/Ucr and urinary NAG/Ucr than those with higher. At the time of kidney biopsy, there were no differences in eGFR and UP/UCr between groups in the M, E, and S categories, nor podocyte parameters. However, T1 and T2 had lower eGFR (36.8 vs. 53.8 mL/min/1.73m2, p<0.05) and higher urinary NAG/Cre (0.0131 vs. 0.0077 IU/mgCr, p<0.05) versus T0. There was no difference in glomerular volume (2.65 v.s. 2.69 x 106 μm3), but podocyte number and density was lower in T1 and T2 (199 v.s. 218 per glomeruli, 162 v.s. 107 per ×106 μm3, respectively). In addition, urinary NAG/UCr was higher (0.0095 v.s. 0.0061 IU/mgCr, p<0.05) and podocyte volume was smaller in C1 and C2 compared to C0 (2905 v.s. 3395 μm3). Conclusion: Podometrics correlated well with clinical characteristics and the Oxford classification at the time of kidney biopsy in IgAN patients. Notably, the association between podometrics (evaluating glomeruli) and the T category (presence or absence of tubular lesions) is intriguing and warrants further investigation, including its relationship to prognosis.