DOI: 10.1001/jamainternmed.2026.0996 ISSN: 2168-6106

Apolipoprotein L1 Gene Genotype and Kidney Outcomes After Living Kidney Donation

Chi-yuan Hsu, Ying Gao, Barry I. Freedman, Mitchell R. Lunn, Anthony N. Muiru, Mark A. Schnitzler, Jasmin Divers, Roslyn B. Mannon, Nicholette D. Palmer, Amy B. Karger, Krista L. Lentine, Meyeon Park, , Gaurav Agarwal, Brad C. Astor, Kelly A. Birdwell, Daniel C. Brennan, Jonathan Bromberg, Darshana M. Dadhania, Mona Doshi, Samira Farouk, Alessia Fornoni, Rasheed Gbadegesin, Chi-yuan Hsu, Bruce Julian, Krista L. Lentine, Roslyn B. Mannon, Sumit Mohan, Barbara Murphy, Kenneth Newell, Mariella Ortigosa-Goggins, Meyeon Park, Stephen Pastan, Emilio D. Poggio, Amber Reeves-Daniel, Sylvia E. Rosas, Deirdre Sawinski, Matthew R. Weir, Paul L. Kimmel, Jonah Odim, Afshin Parsa, Amir Alexander, Benjamin Bagwell, Tim Craven, Elling Eidbo, Barry I. Freedman, Michael Gautreaux, KaShawna Guy, Carl Langefeld, Lijun Ma, Brian Moore, Nicholette Palmer, David Reboussin, Laurie P. Russell, S. Carrie Smith, Robert J. Stratta, Ana Iltis, Nichole Jefferson, Glenda V. Roberts, Marva Moxey-Mims
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Importance

Accurate understanding of long-term risks after living kidney donation is critical to inform evidence-based policies for donor candidate evaluation and selection.

Objective

To determine whether apolipoprotein L1 gene ( APOL1 ) polymorphisms were associated with worse kidney function after living kidney donation.

Design, Setting, and Participants

This retrospective cohort study included all living US kidney donors who donated from January 2000 to December 2008, whose contact information was obtained from the Scientific Registry of Transplant Recipients. After using online search tools to update addresses and telephone numbers, Black and White US living kidney donors who donated during this period were invited to participate. Enrolled study participants had home-based research visits conducted by a subcontract agency between March 2020 and March 2024. Final data analysis was conducted from April 2024 until February 2026.

Exposures

APOL1 polymorphisms and race.

Main Outcomes and Measures

The primary outcome was an estimated glomerular filtration rate (eGFR) of less than 45 mL/min/1.73 m 2 by serum creatinine at the time of home-based research visits. Additional outcomes were an eGFR of less than 60 mL/min/1.73 m 2 , urinary albumin-creatinine levels of 30 or greater or 300 or greater mg/g, and hypertension.

Results

A total of 445 Black kidney donors (295 female individuals [66%]; mean [SD] age, 38 [10] years) and 208 White kidney donors (141 female individuals [68%]; mean [SD] age, 44 [10] years) were enrolled. Sixty-eight Black donors (15.3%) had APOL1 high-risk genotypes (G1/G1, G2/G2, or G1/G2). Home-based research study visits occurred a median (IQR) of 18.5 (16.9-20.5) years after donation. Forty-six of all participants (7.0%) were noted to have an eGFR of less than 45 mL/min/1.73 m 2 . Black kidney donors with APOL1 high-risk genotypes had a higher risk of developing an eGFR of less than 45 mL/min/1.73 m 2 than Black kidney donors without APOL1 high-risk genotypes (relative risk, 2.31; 95% CI, 1.16-4.61; P  = .02) (after adjustment for predonation eGFR: relative risk, 1.91; 95% CI, 0.90-4.03; P  = .09).

Conclusions and Relevance

The study found that the APOL1 genotype is a risk factor for reduced kidney function postdonation. These results suggest that all Black individuals who are living donor candidates in the US should undergo APOL1 genotyping for better risk stratification.

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