Kidney Week

Abstract: TH-PO1069

Disease Progression in Patients with Two APOL1 Variants and Proteinuric CKD from the AASK, CRIC, and FSGS-CT Datasets

Session Information

• CKD Progression and Complications: Diagnosis, Prognosis, Risk Factors
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Lipkowitz, Michael, Georgetown University Medical Center, Washington, District of Columbia, United States

Michael Lipkowitz,

• Manos, George, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

George Manos,

• Gawade, Prasad L., Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Prasad L. Gawade,

• Eagan, Will A., Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Will A. Eagan,

• Yang, Yuan, Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Yuan Yang,

• Egbuna, Ogo I., Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, United States

Ogo I. Egbuna,

• Chertow, Glenn, Stanford University School of Medicine, Palo Alto, California, United States

Glenn Chertow,

Background

Two variants in Apolipoprotein L1 (APOL1) lead to proteinuric chronic kidney disease (CKD) referred to as APOL1-mediated kidney disease (AMKD). Disease progression in persons with two APOL1 variants and proteinuric CKD is not well-understood.

Methods

We analyzed data from non-diabetic patients with two APOL1 variants and proteinuric CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK), Chronic Renal Insufficiency Cohort (CRIC) study, and Focal Segmental Glomerulosclerosis Clinical Trial (FSGS-CT). The analysis included participants in AASK and CRIC with urine protein to creatinine ratio (UPCR) ≥0.7 g/g and participants in FSGS-CT with UPCR ≥1.0 g/g. Baseline age, sex, UPCR, and estimated glomerular filtration rate (eGFR) were determined at enrollment. For each data set, we derived an annual eGFR slope estimate as related to persistent proteinuria, median time to end-stage kidney disease (ESKD), and median time to composite clinical outcome based on a decline of ≥30% from baseline in eGFR, the onset of ESKD, or death.

Results

A total of 38 patients from AASK, 47 patients from CRIC, and 27 patients from FSGS-CT were found to have two APOL1 variants, CKD, and proteinuria. The estimated annual eGFR slope in AASK, CRIC, and FSGS-CT was -5.80, -8.55, and -19.08 mL/min/1.73m²/year, respectively. Across all studies, patients had a median time to ESKD of <4 years and a median time to composite clinical outcome of ≤2.14 years.

Conclusion

These results highlight the rapid rate of decline in kidney function in patients with AMKD relative to other glomerular diseases and may inform the design of clinical trials testing the safety and efficacy of APOL1-targeted therapies.

Funding

• NIDDK Support – Vertex Pharmaceuticals Incorporated