APOL1 risk variants, incident proteinuria, and subsequent eGFR decline in blacks with hypertension-attributed CKD

Teresa K. Chen, Adrienne Tin, Carmen A. Peralta, Lawrence J. Appel, Michael J. Choi, Michael S. Lipkowitz, Cheryl A. Winkler, Michelle M. Estrella

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background and objectives The natural history of kidney disease among blacks who carry the APOL1 high-risk variants varies, with only a subgroup progressing to ESRD. We aimed to determine whether the APOL1 risk variants are associated with incident proteinuria in the context of hypertension-attributed CKD, and whether subsequent kidney function decline after the onset of proteinuria differs by APOL1 risk status. Design, setting, participants, & measurements Using Cox models, we studied the association between APOL1 risk status and incident proteinuria (defined as a doubling of urine protein-to-creatinine ratio to a level ≥0.22 g/g creatinine) among African-American Study of Kidney Disease and Hypertension (AASK) trial participants with APOL1 genotyping and without proteinuria at baseline. Results Of the 480 participants in our study, 82 (17%) had the high-risk genotypes (2 alleles), and 254 (53%) developed proteinuria over a median follow-up of 6.8 years. At baseline, mean eGFR was lower in the APOL1 high-risk group compared with the low-risk group (0 or 1 allele; 49.6 versus 53.2 ml/min per 1.73 m2, respectively; P=0.02), but median proteinuria was similar (0.04 g/g creatinine for both groups; P=0.43). Individuals with the high-risk genotypes were 1.72-fold more likely to develop incident proteinuria compared with those with the low-risk genotypes (95% confidence interval, 1.27 to 2.32), independent of age, sex, ancestry, baseline eGFR, baseline systolic BP, and randomized treatment groups. Although eGFR declined faster after the onset of proteinuria, this rate did not differ significantly by APOL1 risk status. Conclusions Among blacks with established moderate CKD, the APOL1 high-risk variants are associated with greater risk of incident proteinuria. After proteinuria onset, kidney function declines more rapidly but does not differ by APOL1 risk status. This suggests that factors that lead to proteinuria, beyond APOL1, may additionally drive CKD progression.

Original languageEnglish (US)
Pages (from-to)1771-1777
Number of pages7
JournalClinical Journal of the American Society of Nephrology
Volume12
Issue number11
DOIs
StatePublished - Nov 7 2017

Keywords

  • AASK (African American study of kidney disease and hypertension)
  • African Americans
  • Alleles
  • Apo L1
  • BP
  • CKD
  • Chronic
  • Chronic
  • Follow-up studies
  • GRF
  • Genotype
  • Humans
  • Hypertension
  • Kidney failure
  • Proportional hazards models
  • Proteinuria
  • Renal insufficiency
  • United States
  • creatinine

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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