The Correlation Between Podocyte Senescence and the Clinicopathology in Elderly Patients with IgAN

Purpose: IgAN is a common primary glomerular disease, and age may affect its clinical manifestations and progression. However, age-related differences in elderly IgAN, especially the role of podocyte senescence and the cGAS-STING pathway in elderly IgAN patients, remain incompletely understood. Patients and Methods: This retrospective study analyzed 1012 renal biopsy‑confirmed IgAN patients from January 2014 to January 2024, categorized into elderly (≥ 60 years, n=119) and younger (18– 60 years, n=893)) groups after exclusion. Clinical, laboratory, and pathological data were collected. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate prognostic factors. Expression of the cGAS-STING pathway in renal tissues was detected to explore its association with podocyte injury. SASP in serum was detected by ELISA and qPCR. Results: Compared with the young IgAN group, the elderly IgAN group had higher levels of 24-hour urinary protein, urea and creatinine; lower hemoglobin and albumin; more severe tubular atrophy/interstitial fibrosis (T1/2 lesions, 47.1% vs. 23.9%); lower IgA immunofluorescence intensity; and more severe podocyte fusion. Kaplan-Meier analysis showed poorer renal outcomes in the elderly IgAN group ( P < 0.05). Multivariate Cox regression identified podocyte fusion (> 50%) as an independent prognostic factor in the elderly IgAN group (HR=5.72, P =0.011) but not in the young IgAN group.The cGAS-STING pathway is highly expressed in the podocyte of IgAN, especially in the elderly, SASPs in serum, such as IL-6, IL-10, were also highly expressed in the elderly IgAN group, indicating that its activation is related to severe podocyte fusion, elevated proteinuria, and impaired renal function. Conclusion: Elderly IgAN patients exhibit distinct clinicopathological features dominated by chronic lesions and podocyte injury. Severe podocyte fusion (> 50%) is a critical independent prognostic factor for this population. The cGAS-STING pathway may mediate age-related podocyte senescence and injury, representing a potential therapeutic target for elderly IgAN patients.