Abstract Background Renal involvement is a frequent and often severe manifestation of systemic diseases, including autoimmune, metabolic, vascular, and hematologic conditions. The kidney’s unique vascular and structural features render it particularly vulnerable to systemic insults. Renal pathology not only reflects the nature of the underlying disorder but also plays a pivotal role in diagnosis, risk stratification, and therapeutic planning. Objective This narrative review provides a comprehensive overview of the major histopathological patterns encountered in systemic diseases affecting the kidney, highlighting the diagnostic utility of renal biopsy and ancillary studies, and addressing current diagnostic challenges. Methods We examined the renal pathological hallmarks of key systemic diseases, including lupus nephritis, ANCA-associated vasculitis, diabetic nephropathy, amyloidosis, and hypertensive nephrosclerosis. Diagnostic tools such as light microscopy, immunofluorescence, electron microscopy, and immunohistochemistry were reviewed in the context of their application to biopsy interpretation. Results While each disease exhibits characteristic morphologic features, overlapping patterns and nonspecific findings frequently complicate interpretation. Challenges such as masked immune deposits, limited sampling, and coexisting pathologies may lead to misclassification. Accurate diagnosis requires correlation with clinical, serologic, and imaging findings in a multidisciplinary context. Conclusion Renal biopsy remains the gold standard for evaluating systemic diseases with renal involvement. Integrating traditional histopathology with emerging technologies—such as digital image analysis, molecular typing, and AI-based pattern recognition—holds promise for improved classification, prognostication, and personalized patient care.
Rezaei et al. (Mon,) studied this question.