Monogenic diseases account for 10-20% of chronic kidney disease (CKD) in adults. Their importance is increasingly appreciated in general nephrology, facilitated by more widespread access to genomic testing and expanding gene panels. The 2024 KDIGO clinical practice guideline for evaluation and management of CKD emphasises the importance of considering genetic testing, particularly in the context of unexplained CKD (CKDx) when histological evaluation does not identify a precise aetiology. Identifying a genetic cause provides a definitive diagnosis and shapes patient management including access to disease-specific therapies, screening for extra-renal manifestations, early initiation of renoprotective measures, avoiding ineffective and potentially harmful treatments, a better understanding of the likely disease course including risk of recurrence following transplantation, and reproductive counselling. Despite this, genetic kidney disease may be overlooked due to lack of physician or pathologist familiarity, lack of clear family history, genotype-phenotype heterogeneity, and/or atypical presentations. The pathologist has an important role in identifying potential cases of genetic kidney disease as part of routine kidney biopsy assessment. Histology can either strengthen the case for a suspected genetic disease, or-not infrequently-be the first evidence of a potential underlying genetic cause. The pathologist participates in the clinicopathological correlation (CPC) meeting discussing evidence to identify patients in whom genetic testing would be appropriate. This review provides pathologists and nephrologists with an overview of the different histological patterns associated with genetic kidney disease, and outlines a practical framework for reporting kidney biopsies, receiving the reports, and/or participating in CPC discussions.
Paterson et al. (Wed,) studied this question.