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Association Between APOL1 Genotype and Kidney Diseases and Annual Kidney Function Change: A Systematic Review and Meta-Analysis of the Prospective Studies

Authors Jagannathan R, Rajagopalan K, Hogan J, Hart A, Newell KA, Pastan SO, Patzer RE

Received 18 December 2020

Accepted for publication 23 February 2021

Published 7 April 2021 Volume 2021:14 Pages 97—104

DOI https://doi.org/10.2147/IJNRD.S294191

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Pravin Singhal


Ram Jagannathan,1 Kanya Rajagopalan,2 Julien Hogan,3,4 Allyson Hart,5,6 Kenneth A Newell,4 Stephen O Pastan,7 Rachel E Patzer4,7,8

1Department of Medicine, Division of Hospital Medicine, Emory University School of Medicine, Atlanta, GA, USA; 2Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA; 3Pediatric Nephrology Department, Robert Debre University Hospital, Paris, 75019, France; 4Department of Surgery, Division of Transplantation, Emory University School of Medicine, Atlanta, GA, USA; 5Division of Nephrology, Department of Medicine, Hennepin Healthcare, Minneapolis, MN, USA; 6University of Minnesota Medical School, Minneapolis, MN, USA; 7Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; 8Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

Correspondence: Ram Jagannathan
Department of Medicine, Division of Hospital Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA
Email [email protected]

Background: Two coding risk variants in the Apo L1 gene (APOL1) underlie most of the excess risk for kidney diseases in recent African ancestry patients. Strength and consistency of the relationship between APOL1 high-risk genotypes and the risk of chronic kidney diseases (CKD) and end-stage renal disease (ESRD) are not uniform.
Objective: To conduct a systematic review and meta-analysis of prospective studies assessing the association of APOL1 genotypes and the risk of developing CKD, ESRD, and CKD to ESRD in adults.
Methods: Systematic search of MEDLINE, EMBASE, and Google Scholar was performed for prospective studies assessing the associations between APOL1 genotypes and CKD, ESRD, and progression from CKD to ESRD. Secondary analyses were to evaluate the annual kidney function change by APOL1 gene status. Random effects models were used to estimate pooled risk ratios (RRs) and weighted mean differences for outcomes of interest.
Results: The search yield 10 prospective during a follow-up period ranging from 4.4 to 25 years. The high-risk APOL1 genotype was associated with the incidence of CKD (RR:1.41[95% CI: 1.14– 1.75]), the progression from CKD to ESRD (RR: 1.70[95% CI:1.44; 2.01]) compared with the low-risk APOL1 genotype. There was no appreciable association between high-risk APOL1 genotype with the incidence of ESRD. Furthermore, high-risk APOL1 genotype was associated with a marginal decrement in the annual eGFR decline (− 0.55[95% CI: − 0.94 to − 0.16]) mL/min/1.73m2 compared with low-risk APOL1 genotype status.
Conclusion: In summary, African Americans carrying APOL1 high-risk genotypes are at increased risk of developing CKD and ESRD. Given that the APOL1 risk alleles are common among individuals with African ancestry, with ∼ 18% of African Americans carrying high-risk alleles, these findings highlight the potential identification of subgroups of patients who may benefit from APOL1 screening and developing culturally-appropriate interventions.

Keywords: APOL1, chronic kidney disease, end-stage renal diseases, disparities, African Americans

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