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Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes.

Publication ,  Journal Article
Kallash, M; Wang, Y; Smith, A; Trachtman, H; Gbadegesin, R; Nester, C; Canetta, P; Wang, C; Hunley, TE; Sperati, CJ; Selewski, D; Ayoub, I ...
Published in: Clin J Am Soc Nephrol
March 1, 2023

BACKGROUND: FSGS is a heterogeneous diagnosis with a guarded prognosis. Polymorphisms in the apolipoprotein L1 ( APOL1 ) gene are associated with developing FSGS and faster progression to kidney failure in affected patients. Better understanding the natural history of patients with FSGS and APOL1 risk alleles is essential to improve patient care and support the design and interpretation of interventional studies. The objective of this study was to evaluate the quantitative association between APOL1 and kidney disease progression and the interaction with other clinical and laboratory factors. METHODS: CureGN cohort study participants with biopsy diagnosis of FSGS, regardless of self-identified race, were included. The exposure of interest was two APOL1 risk alleles (high risk) versus zero to one risk alleles (low risk). The primary outcome was eGFR slope categorized as rapid progressor (eGFR slope ≤-5 ml/min per year), intermediate progressor (slope between 0 and -5), or nonprogressor (slope ≥0). Multivariable ordinal logistic and linear regressions were used for adjusted analyses. Missing data were addressed using multiple imputation. RESULTS: Of 650 participants, 476 (73%) had genetic testing, among whom 87 (18%) were high risk. High-risk participants were more likely to have lower median eGFR (62 [interquartile range, 36-81] versus low-risk participants 76 ml/min per 1.73 m 2 [interquartile range, 44-106]; P <0.01). In adjusted analysis, the odds of more rapid progression of eGFR was 2.75 times higher (95% confidence interval, 1.67 to 4.53; P <0.001) in the high-risk versus low-risk groups. CONCLUSIONS: In patients with FSGS, high-risk APOL1 genotype is the predominant factor associated with more rapid loss of kidney function.

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Published In

Clin J Am Soc Nephrol

DOI

EISSN

1555-905X

Publication Date

March 1, 2023

Volume

18

Issue

3

Start / End Page

344 / 355

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Risk Factors
  • Humans
  • Glomerulosclerosis, Focal Segmental
  • Genotype
  • Cohort Studies
  • Apolipoproteins
  • Apolipoprotein L1
  • 4202 Epidemiology
  • 3202 Clinical sciences
 

Citation

APA
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ICMJE
MLA
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Kallash, M., Wang, Y., Smith, A., Trachtman, H., Gbadegesin, R., Nester, C., … CureGN*, . (2023). Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes. Clin J Am Soc Nephrol, 18(3), 344–355. https://doi.org/10.2215/CJN.0000000000000069
Kallash, Mahmoud, Yujie Wang, Abigail Smith, Howard Trachtman, Rasheed Gbadegesin, Carla Nester, Pietro Canetta, et al. “Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes.Clin J Am Soc Nephrol 18, no. 3 (March 1, 2023): 344–55. https://doi.org/10.2215/CJN.0000000000000069.
Kallash M, Wang Y, Smith A, Trachtman H, Gbadegesin R, Nester C, et al. Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes. Clin J Am Soc Nephrol. 2023 Mar 1;18(3):344–55.
Kallash, Mahmoud, et al. “Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes.Clin J Am Soc Nephrol, vol. 18, no. 3, Mar. 2023, pp. 344–55. Pubmed, doi:10.2215/CJN.0000000000000069.
Kallash M, Wang Y, Smith A, Trachtman H, Gbadegesin R, Nester C, Canetta P, Wang C, Hunley TE, Sperati CJ, Selewski D, Ayoub I, Srivastava T, Mottl AK, Kopp J, Gillespie B, Robinson B, Chen D, Steinke J, Twombley K, Reidy K, Mucha K, Greenbaum LA, Blazius B, Helmuth M, Yonatan P, Parekh RS, Hogan S, Royal V, D’Agati V, Chishti A, Falk R, Gharavi A, Holzman L, Klein J, Smoyer W, Kretzler M, Gipson D, Kidd JM, CureGN*. Rapid Progression of Focal Segmental Glomerulosclerosis in Patients with High-Risk APOL1 Genotypes. Clin J Am Soc Nephrol. 2023 Mar 1;18(3):344–355.

Published In

Clin J Am Soc Nephrol

DOI

EISSN

1555-905X

Publication Date

March 1, 2023

Volume

18

Issue

3

Start / End Page

344 / 355

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Risk Factors
  • Humans
  • Glomerulosclerosis, Focal Segmental
  • Genotype
  • Cohort Studies
  • Apolipoproteins
  • Apolipoprotein L1
  • 4202 Epidemiology
  • 3202 Clinical sciences