Monogenic Kidney Diseases in Adults With Chronic Kidney Disease (CKD)

Dtsch Arztebl Int. 2024 Oct 4:(Forthcoming):arztebl.m2024.0120. doi: 10.3238/arztebl.m2024.0120. Online ahead of print.

Abstract

Background: According to current evidence, every 10th to 11th adult with chronic kidney disease (CKD) has a monogenic disease of the kidney.

Methods: This review is based on reported studies in which molecular genetic diagnostic techniques were used to investigate monogenic kidney diseases in adults with CKD. The studies were identified by a selective literature search using predefined criteria.

Results: In 12 selected studies, diagnostic variants of 179 different genes were identified in 1467 out of 6607 study participants with CKD (22.2%). More than 60% of these variants affected 8 genes (PKD1, PKD2, COL4A3, COL4A4, COL4A5, UMOD, MUC1, HNF1B). Three diseases are associated with these genes: autosomal dominant polycystic kidney disease (ADPKD), Alport syndrome, and autosomal dominant tubulo-interstitial kidney disease (ADTKD). Physicians treating patients with CKD should be alert to the presence of any red flags, such as onset at a young age, a positive family history, or hematuria of unknown cause. When a genetic etiology is suspected, a specialized work-up is indicated, often including a molecular genetic investigation. A positive genetic finding usually leads to a modification of the patient's specific diagnosis and/or treatment.

Conclusion: Awareness of the high prevalence of monogenic kidney diseases in adults with CKD and alertness to their suggestive clinical features are crucial for the timely initiation of targeted diagnostic testing. The molecular genetic identification of these diseases is a prerequisite for appropriate patient management.

Publication types

  • Review