Kidney Week

Abstract: SA-PO0655

Phenotype-Genotype Characteristics and Disease Progression of FAN1 Karyomegalic Interstitial Nephritis

Session Information

• Monogenic Kidney Diseases: Tubular and Other
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases

Authors

• Clince, Michelle, Beaumont Hospital, Dublin, Leinster, Ireland

Michelle Clince, DrMed, MBChB

• Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Leinster, Ireland

Elhussein Aamir Elzein Elhassan, MBBS, MS, MSc

• McAnallen, Susan Marie, St James's Hospital, Dublin, Leinster, Ireland

Susan Marie McAnallen, MBChB

• Kidd, Kendrah O., Wake Forest University, Winston-Salem, North Carolina, United States

Kendrah O. Kidd, PhD

• Claes, Kathleen, UZ Leuven, Leuven, Flanders, Belgium

Kathleen Claes, MD, MSc, PhD

• Chung, Byung ha, The Catholic University of Korea, Seoul, Korea (the Republic of)

Byung ha Chung, MD, PhD

• Halbritter, Jan, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Jan Halbritter, MD

• Gale, Daniel P., University College London, London, England, United Kingdom

Daniel P. Gale, MA, MBChB, PhD

• Alawi, Intisar, The Royal Hospital, Muscat, Oman

Intisar Alawi, PhD

• Patel, Chirag, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Chirag Patel, MD, MBBS

• Mallett, Andrew John, James Cook University, Townsville City, Queensland, Australia

Andrew John Mallett, MBBS, PhD, FASN

• Faguer, Stanislas, Centre Hospitalier Universitaire de Toulouse, Toulouse, Occitanie, France

Stanislas Faguer, MD, PhD

• Knebelmann, Bertrand, Hopital Necker-Enfants Malades Service de Genetique Clinique, Paris, Île-de-France, France

Bertrand Knebelmann, MD, PhD

• Goucha Louzir, Rim, Centre Hospitalier Universitaire Mongi Slim, La Marsa, Tunis, Tunisia

Rim Goucha Louzir, MD

• Jerbi, Mouna, Centre Hospitalier Universitaire Mongi Slim, La Marsa, Tunis, Tunisia

Mouna Jerbi, DrMed, PhD, DrPH

• Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Friedhelm Hildebrandt, MD

• Sayer, John Andrew, Newcastle University, Newcastle upon Tyne, England, United Kingdom

John Andrew Sayer, MBChB, PhD

• Sperati, John, Johns Hopkins University, Baltimore, Maryland, United States

John Sperati, MD

• Zheng, Sijie, The Permanente Medical Group Inc, Oakland, California, United States

Sijie Zheng, MD, PhD, FASN

• Guebessi, Nisrine Bennani, Universite Hassan II de Casablanca, Casablanca, Grand Casablanca, Morocco

Nisrine Bennani Guebessi, MD, DrMed

• De Boeck, Koen, Ziekenhuis aan de Stroom vzw, Antwerp, Flanders, Belgium

Koen De Boeck, DrMed

• Iványi, Béla, Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Orvostudomanyi Kar, Szeged, Csongrád, Hungary

Béla Iványi, MD

• Bleyer, Anthony J., Wake Forest University, Winston-Salem, North Carolina, United States

Anthony J. Bleyer, MD, MS, FASN

• Conlon, Peter J., Beaumont Hospital, Dublin, Leinster, Ireland

Peter J. Conlon, MBChB, FASN

Group or Team Name

• FAN1 Study Group.

Background

Biallelic variants in Fanconi Anaemia-associated Nuclease 1 (FAN1) cause karyomegalic interstitial nephritis (KIN), a rare form of CKD. Given the low number of reported cases of FAN1-KIN, we undertook a global collaboration to identify cases of FAN1-KIN and characterize this disease.

Methods

We performed a cross-sectional study, inviting colleagues and authors of former case reports to complete a survey in REDCap that included data on genetic mutation and the clinical characteristics of FAN1-KIN. Logistic regression model and Kaplan-Meier analysis investigated the associations between clinical outcomes and FAN1 variants.

Results

We identified 86 families (122 individuals) from 22 countries. There were 56 families (83 individuals) with a genetic diagnosis of FAN1-KIN and 30 families (39 individuals) with KIN with no genetic diagnosis. There were 38 distinct FAN1 variants. The median age at presentation was 38.5 years, 62.3% male, 45.8% had liver disease, 39.2% had lung disease, and 6% had cancer. The mean age of kidney failure (KF) was 40.6 ± 9.9 years. Of 115 individuals, 27% had died, at a mean age of 43.9 ± 11.3 years.
At presentation, those with lung disease had worse eGFR compared to those without (25 vs. 36.5 ml/min/1.73 m²; P=0.01), whereas liver disease was not associated with worse eGFR (32 vs. 33 ml/min/1.73 m²; P=0.319). The risk of developing lung disease in patients with p.W707X-FAN1 variant was eightfold greater than in non-p.W707X/p.D873Tfs-FAN1 variants (adjusted odds ratio: 8.26 (95% confidence interval (CI): 1.7 – 40.1); P=0.009). None of the genetic covariates were statistically significant for the progression to KF. Kidney transplant recipients (KTR) had a better survival time compared to those who remained on dialysis (11 years (95% CI: 10 – 14) vs. 4 (95% CI: 3 - 5); Log-rank P=0.0004). 7/26 KTR died of interstitial lung disease/pulmonary infection at a mean duration of 7.8 years post-transplant.

Conclusion

Patients with FAN1-KIN develop KF at a mean age of 40.6 years. Many patients die of lung disease post-transplant.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025ppjtme55