Authors of a morphology-based review propose using kidney biopsy findings to help identify patients who may benefit from genetic testing for monogenic kidney disease. The framework groups biopsy patterns into three categories: 1) findings with a high likelihood of a genetic cause, such as characteristic features of Alport syndrome, Fabry disease, adenine phosphoribosyltransferase deficiency, or lecithin-cholesterol acyltransferase deficiency; 2) patterns that may be either genetic or acquired, such as C3 glomerulopathy, thrombotic microangiopathy, amyloidosis, and oxalate nephropathy; and 3) nonspecific chronic changes such as focal segmental glomerulosclerosis (FSGS) or interstitial fibrosis and tubular atrophy in otherwise unexplained CKD. Even among patients with CKD of unexplained cause, about 17% may have an underlying genetic etiology, underscoring the value of considering inherited disease when biopsy findings and the clinical picture do not fully align.
For clinical practice, the review emphasizes integrating morphology with age at onset, family history, extrarenal features, treatment response, and electron microscopy rather than relying on histology alone. Genetic testing should be considered when characteristic ultrastructural abnormalities are present, when common biopsy patterns lack a clear acquired driver, or when the result could change management. Potential benefits include avoiding ineffective immunosuppression, guiding transplant or donor decisions, identifying treatable inherited disorders, and refining prognosis. In adult-onset FSGS, monogenic causes account for an estimated 10% to 20% of cases, while unusually high diagnostic yields have been reported when nephrotic syndrome and podocyte foot-process effacement do not match expected patterns. The authors ultimately recommend making the possibility of a genetic basis part of routine clinicopathologic reasoning in unexplained kidney disease.
Reference: Paterson AL, Chan MMY, Roufosse C. Genetic kidney disease in adults-the pathologists’ perspective. Nephrol Dial Transplant. 2026 Jul 31;41(8):1421-1428. doi: 10.1093/ndt/gfag047.
