High burden of kidney involvement in neuronal intranuclear inclusion disease

Background: GGC repeat expansions. Renal involvement in NIID is not well understood. Methods: We conducted a cross-sectional study of 96 genetically confirmed NIID patients. Renal function was comprehensively assessed using the estimated glomerular filtration rate (eGFR) derived from the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine equation (CKD-EPI 2021; hereafter EPI-eGFR) and a panel of five urinary biomarkers (microalbumin, transferrin, immunoglobulin G, α1-microglobulin, and α2-macroglobulin). Clinical features, GGC repeat number, and skin intranuclear inclusion count were analyzed for their association with renal function. Renal biopsies from two patients with pre-neurological proteinuria were examined for intranuclear inclusions. Renal biopsies from two patients with pre-neurological proteinuria revealed characteristic p62-positive intranuclear inclusions in tubular and glomerular cells. Conclusion: Kidney involvement is common in this hospital-based NIID cohort, with a substantial proportion showing subclinical renal impairment. Sensitive urinary biomarkers may aid early detection before eGFR declines, with microalbumin showing the highest discriminative ability. Hypertension is a potentially modifiable risk factor for reduced eGFR. Genetic burden and skin inclusion burden do not predict renal outcomes, suggesting that secondary mechanisms drive progression. For patients who present with unexplained renal impairment, pathological examination of renal biopsy specimens for intranuclear inclusions may provide critical diagnostic clues.