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Lookup NU author(s): Professor John SayerORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 International Society of Nephrology. Introduction: Biallelic variants in Fanconi Anemia-associated Nuclease 1 (FAN1) cause karyomegalic tubulointerstitial nephropathy (KIN), a condition poorly characterized in terms of kidney survival, patient survival, and clinical characteristics. Therefore, we undertook a cross-sectional collaborative study to better characterize KIN-FAN1. Methods: To gather data, we distributed a REDCap survey on clinical characteristics and genetic variants of KIN-FAN1 to colleagues and case report authors. Results: Based on the survey, we identified 86 families affected (122 individuals) from 22 countries. There were 56 families (83 individuals) with a genetic diagnosis of KIN-FAN1, including 38 distinct FAN1 variants, and 30 families (39 individuals) with KIN with no predisposing risk factors and without molecular FAN1 testing. The median age at presentation was 38.5 years (interquartile range: 29–43), 62% male. Of the cohort, 46% had asymptomatic elevation of liver function tests, 39% had pulmonary complications, and 6% developed cancer. The median age of kidney failure was 45 years (95% confidence interval (CI): 38–56). Of the cohort, 27.1% died at a median age of 55 years (95% CI: 43–75). Pulmonary complications was/were the cause of death in 15.4% of patients on dialysis and 23.1% of kidney transplant recipients. Compared to other variants, patients with the p.W707X-FAN1 variant were at a significantly higher risk of pulmonary complications (adjusted odds ratio: 8.26 (95% CI: 1.7–40.1) and had a significantly shorter lifespan (hazard ratio: 3.24 (95% CI: 1.13–9.28). No genetic covariates were statistically associated with the progression to kidney failure. Conclusions: Patients with KIN-FAN1 develop kidney failure at a median age of 45 years. Survival is compromised with many dying of pulmonary disease.
Author(s): Clince M, Elhassan EAE, Kidd KO, Malamud E, McAnallen SM, Danial A, Chung BH, Kim M, Sayer JA, Al Alawi I, Bernards J, Jerbi M, Goucha R, Ben Jemaa L, Rejeb I, Patel C, Mallett AJ, Sperati CJ, de Boeck K, Muller M, Stehle T, Guebessi NB, Robert T, Ivanyi B, Csaszar I, Shril S, Zheng S, Mathew GG, Dirim MG, Dirim AB, Mesnard L, Gueguen L, Schafer F, Bergmann C, Gale DP, Halbritter J, Claes KJ, Knebelmann B, Zivna M, Kmoch S, Faguer S, Hildebrandt F, Bleyer AJ, Conlon PJ
Publication type: Article
Publication status: Published
Journal: Kidney International
Year: 2026
Pages: Epub ahead of print
Online publication date: 19/01/2026
Acceptance date: 02/01/2026
Date deposited: 03/03/2026
ISSN (print): 0085-2538
ISSN (electronic): 1523-1755
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.kint.2026.01.001
DOI: 10.1016/j.kint.2026.01.001
Data Access Statement: All available data has been included in this article.
PubMed id: 41565023
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