Genotype-phenotype characteristics and disease progression of FAN1-related karyomegalic tubulointerstitial nephropathy

FAN1-associated karyomegalic interstitial nephropathy is a rare inherited tubulointerstitial kidney disease with limited long-term clinical data. Methods: We compiled and analyzed clinical, genetic, and histopathological information from an international cohort of patients, including data from a systematic literature review and supplementary case records. Results: The disease is characterized by progressive chronic kidney disease frequently leading to kidney failure, accompanied by variable hepatic and pulmonary involvement. Pathogenic FAN1 variants were identified across diverse populations worldwide. Kidney transplantation proved to be an effective treatment without evidence of disease recurrence in the graft, while pulmonary complications represented an important contributor to mortality. Conclusions: FAN1-associated nephropathy is a multisystem disorder with heterogeneous presentation but predictable progression to renal failure. Early genetic diagnosis and multidisciplinary follow-up are essential to optimize patient care and improve understanding of its natural history.