Autosomal Dominant Tubulointerstitial Kidney Disease: Approach to Diagnosis

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a genetically heterogeneous disorder characterized by progressive chronic kidney disease, primarily affecting the tubules and interstitium. It results from pathogenic variants in several known genes, including UMOD, mucin-1 (MUC1), REN, APOA4, and others. Despite its clinical significance, ADTKD is often under-recognized due to nonspecific histopathological and clinical features and limited referral for genetic testing, which remains the gold standard for diagnosis. In addition, due to technical difficulties, genetic testing for ADTKD-MUC1 is not currently performed in multigene panels and cannot be obtained through whole exome or genome sequencing. Recent advances in kidney disease research underscore the critical role of comprehensive genetic testing in elucidating the molecular etiology of unsolved cases. However, challenges persist in the diagnosis of specific ADTKD subtypes, particularly those caused by pathogenic MUC1 pathogenic variants. This review provides a detailed analysis of the genetic basis, clinical presentation, and diagnostic approaches for ADTKD, with an emphasis on the limitations in current testing methodologies for ADTKD-MUC1. We further explore recent advancements in our understanding of ADTKD and highlight future directions for improving diagnostic accuracy and patient care through enhanced genetic testing technologies.