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Kidney Week

Abstract: FR-PO1138

Genetic Evaluation of Living Kidney Donor Candidates for Complement-Mediated Kidney Diseases: Challenges in Variant Interpretation

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Caliskan, Yasar, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Oto, Ozgur Akin, Istanbul Universitesi, Fatih, Istanbul, Turkey
  • Garg, Neetika, University of Wisconsin System, Madison, Wisconsin, United States
  • Velioglu, Arzu, Marmara Universitesi, Istanbul, Turkey
  • Ural, Zeynep, Gazi Universitesi, Ankara, Turkey
  • Radunovic, Danilo, Klinicki Centar Crne Gore, Podgorica, Podgorica Municipality, Montenegro
  • Trujillo, Hernando, Hospital Universitario 12 de Octubre, Madrid, Community of Madrid, Spain
  • Kousios, Andreas, Nefrontida Medical Center, Nicosia, Cyprus
  • Sayer, John Andrew, Newcastle University, Newcastle upon Tyne, England, United Kingdom
  • Alhamad, Tarek, Washington University in St Louis, St. Louis, Missouri, United States
  • Alfieri, Carlo, Universita degli Studi di Milano, Milan, Lombardy, Italy
  • Yazici, Halil, Istanbul Universitesi, Fatih, Istanbul, Turkey
  • Mejia, Christina Irene, Johns Hopkins University, Baltimore, Maryland, United States
  • Viklicky, Ondrej, Institut klinicke a experimentalni mediciny, Prague, Czechia
  • Jittirat, Arksarapuk, UH Cleveland Medical Center, Cleveland, Ohio, United States
  • Daloul, Reem, Allegheny Health Network, Pittsburgh, Pennsylvania, United States
  • Soliman, Karim, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Ma, Becky Mingyao, The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
  • Castellano, Giuseppe, Universita degli Studi di Milano, Milan, Lombardy, Italy
  • Thomas, Christie P., University of Iowa Health Care, Iowa City, Iowa, United States
  • Mannon, Roslyn B., University of Nebraska System, Lincoln, Nebraska, United States
  • Lentine, Krista L., Saint Louis University, St. Louis, Missouri, United States
Background

Atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) are rare complement-mediated kidney diseases with limited guidance for related living kidney donor candidate (LKDC) evaluation. Using the international LDGen registry, we characterized genetic testing practices in LKDC evaluations for CMKD.

Methods

We analyzed de-identified cross-sectional data from the LDGen REDCap registry (June 2023-November 2025). Eligible cases included LKDC evaluations involving genetic testing, family history of genetic kidney disease, or donation to related recipients with kidney disease of unknown etiology. Clinical characteristics, genetic testing strategies, and donor outcomes were compared between aHUS and C3G cases.

Results

Among 1,011 LKDC evaluations across 24 LDGen centers, 63 (6%) involved CMKD, including 41 (65%) aHUS and 22 (35%) C3G cases. Demographics were similar between groups. Genetic testing was more common in aHUS than C3G evaluations (63% vs. 18%, p<0.001), with recipient-first testing also more frequent in aHUS (61% vs. 14%, p<0.001) (Table 1). Subsequent donor testing occurred more often in aHUS cases (37% vs. 9%, p=0.02). Among 17 LKDCs tested after recipient evaluation, 11 (65%) had genetic findings, including variants in CFH, CFHR3, CFI, COL4A4, and C3. Overall, 5 LKDCs were excluded from donation because of genetic findings, including CFH and CFHR3 benign(B)/likely benign (LB) variants shared with related recipients (Table 2).

Conclusion

Genetic testing during LKDC evaluation was more common in aHUS than C3G and was usually initiated in recipients before donor evaluation. Frequent exclusion of donor candidates based on B/LB variants or VUS highlights the need for standardized approaches to genetic testing, variant interpretation, and counseling in CMKD.