Kidney Week

Abstract: FR-PO0154

Natural History Study of Patients with Proteinuric APOL1-Mediated Kidney Disease (AMKD) in BioVU and the Million Veteran Program (MVP)

Session Information

• Hereditary Glomerular and Tubulointerstitial Kidney Diseases
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Mamak, Fatih, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Fatih Mamak, MD

• Bidhan, Sourabh, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Sourabh Bidhan, MD, MBBS

• Yu, Zhihong, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Zhihong Yu, MS, PhD

• Triozzi, Jefferson Lorenzo, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Jefferson Lorenzo Triozzi, MD

• Wilson, Otis D., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Otis D. Wilson

• Chen, Hua-Chang, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Hua-Chang Chen, PhD

• Tao, Ran, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Ran Tao

• Hung, Adriana, VA Tennessee Valley Healthcare System, Nashville, Tennessee, United States

Adriana Hung, MD, MPH

Group or Team Name

• KidneyPhenGen and Vanderbilt Precision Nephrology

Background

APOL1 high-risk (HR) genotypes (two copies) are strongly associated with the risk of AMKD in individuals of African ancestry. Biallelic carriers that develop proteinuria are at the highest risk of progression. However, longitudinal studies describing disease progression for proteinuric AMKD have been limited by sample size and have not studied patients with Type 2 diabetes (DM).

Methods

We studied 1,546 patients of African ancestry with APOL1 HR, enrolled in MVP (n=1,265) or the Vanderbilt BioVU (n=281), with urine albumin-creatinine ratio (UACR) ≥321 mg/g (stage A3 CKD), using different baseline eGFR cut-off < 90, <75 and <60 ml/min/m². Outcomes included the slope of eGFR decline over the entire study follow up and the median time to a composite endpoint of ≧30% decline, ESKD or death. Subgroup analysis was done by DM.

Results

Mean (SD) age was 61 (12) yrs, 1330 (86%) were male, 1000 (65%) had DM. Mean baseline eGFR was 54 (18) ml/min, mean UACR was 846.9 (817.3) mg/g, 95% had hypertension, 49% CVD and 68 (~4%) FSGS, 78% were in RAASi and 5% on SGLT2i. The mean(SD) follow up was 3.6 (3.3) years. For patients with baseline UACR >= 321 mg/g, almost all subgroups (non-DM (NDM) and DM and at different eGFR cut-off) had a fast eGFR decline > 3 ml/min per year, albeit faster in patients with DM (Table 1). For the composite endpoint, the median time to event was from 3 to 5 years for all subgroups if GFR <75ml/min and for MVP, even at eGFR< 90 ml/min: 4.0 (95% CI: 1.8, 8.2) and 3.1 (95%CI: 1.4, 5.5) years, for NDM and DM respectively. For BioVU in the GFR <90 ml/min the time to event was longer in NDM: 7.2 (95%CI: (4.0, 10.2) and DM: 3.4 (95% CI: 2.8, 4.9) years.

Conclusion

Biallelic carriers with proteinuria, at an UACR >321 mg/g, experience fast eGFR decline of about ≧3 ml/min, with a short median survival time to a composite outcome of 30% decline in GFR, ESRD or death of 3 to 5 years for most subgroups. Results were independent of DM status. Additional studies evaluating higher risk subgroups and incorporating genetic modifiers are needed.

Acknowledgment

Dr. Mamak and Dr. Bidham are co-lead
MVP work is supported by a VA Merit award CX001897 (Hung)

Table 1. Annual eGFR Slope by Subgroups

Funding

• Veterans Affairs Support