Kidney Week

Abstract: TH-OR99

Associations between APOL1 Genotypes and Major Adverse Cardiovascular Events (MACE) in Proteinuric Glomerulopathies: A CureGN and NEPTUNE Study

Session Information

• Podocytopathies and Membranous Nephropathy: Clinical Advances
  October 24, 2024 | Location: Room 1, Convention Center
  Abstract Time: 05:50 PM - 06:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Schuchman, Matthew, Cohen Children's Medical Center, Queens, New York, United States

Matthew Schuchman

• Mathew, Roy O., VA Loma Linda Healthcare System, Loma Linda, California, United States

Roy O. Mathew, MD, FASN

• Smith, Abigail R., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Abigail R. Smith, PhD

• Gonzalez-Vicente, Agustin, Case Western Reserve University, Cleveland, Ohio, United States

Agustin Gonzalez-Vicente, PhD

• Gadegbeku, Crystal A., Cleveland Clinic, Cleveland, Ohio, United States

Crystal A. Gadegbeku, MD, FASN

• Adler, Sharon G., Harbor-UCLA Medical Center, Torrance, California, United States

Sharon G. Adler, MD, FASN

• Glenn, Dorey A., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Dorey A. Glenn, MD, MPH

• Waldman, Meryl, National Institutes of Health, Bethesda, Maryland, United States

Meryl Waldman, MD

• Bitzer, Markus, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Markus Bitzer, MD

• Alakwaa, Fadhl, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Fadhl Alakwaa, PhD

• Kerlin, Bryce A., Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Bryce A. Kerlin, MD

• Nachman, Patrick H., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States

Patrick H. Nachman, MD, FASN

• Robinson, Bruce M., University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Bruce M. Robinson, MD, MS, FASN

• Khalid, Myda, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana, United States

Myda Khalid, MD

• Derebail, Vimal K., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States

Vimal K. Derebail, MD, MPH, FASN

• Srivastava, Tarak, Children's Mercy Kansas City, Kansas City, Missouri, United States

Tarak Srivastava, MD, FASN

• Hall, Gentzon, Duke Health, Durham, North Carolina, United States

Gentzon Hall, MD, PhD, FASN

• Tuttle, Katherine R., Providence St Joseph Health, Renton, Washington, United States

Katherine R. Tuttle, MD, FASN

• O'Shaughnessy, Michelle M., University College Cork, Cork, Cork, Ireland

Michelle M. O'Shaughnessy, MD, MBChB, MS, FASN

• Cara-Fuentes, Gabriel M., Nationwide Children's Hospital, Columbus, Ohio, United States

Gabriel M. Cara-Fuentes, MD, PhD

• Roehm, Bethany Angela, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Bethany Angela Roehm, MD, MS

• Zee, Jarcy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Jarcy Zee, PhD

• Sethna, Christine B., Cohen Children's Medical Center, Queens, New York, United States

Christine B. Sethna, MD, MEd

Group or Team Name

• On behalf of the NEPTUNE Cardiovascular Working Group.

Background

Patients with proteinuric glomerulopathies are at increased risk for cardiovascular disease, but the relationship between APOL1 genotype and MACE remains poorly understood.

Methods

Participants enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) or Cure Glomerulonephropathy (CureGN) with completed APOL1 genotyping and biopsy-proven minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy or IgA nephropathy were included. Cox regression with an outcome of MACE, defined as time from enrollment to first stroke, heart failure or coronary artery disease (CAD), was conducted by APOL1 genotype (high risk defined as having two copies of G1 and/or G2 risk variants). Models were adjusted for age, sex, obesity, glomerular diagnosis, urine protein:creatinine and glomerular filtration rate (eGFR) at enrollment, prior MACE and time from biopsy to enrollment.

Results

Among 3224 participants, 296 (9.2%) individuals (age 31.3 ± 20 yrs, 80% self-identified Black, 34.7% children, median 61.3 months follow-up) had the high-risk APOL1 genotype. In the full cohort, 134 individuals (4%) experienced MACE, with a total of 158 events (39 stroke, 47 heart failure, 72 CAD). After adjustments, high-risk APOL1 genotype was significantly associated with MACE (HR 2.84, 95% CI 1.56-5.15, p<0.001) (Figure).

Conclusion

Among participants in two large observational studies of proteinuric glomerular disease, high risk APOL1 genotype had greater than a two-fold effect on MACE, independent of kidney disease risk factors. Future analyses are required to confirm this relationship at the time of diagnosis.

Funding

• NIDDK Support