Real-World AMKD Data Highlight Quick Progression, Unmet Needs

Almost half of patients in the US with APOL1-mediated kidney disease (AMKD) had progressed to stage 4 or 5 chronic kidney disease (CKD) by a mean age of 45.6 years, and about one-third received renin-angiotensin-aldosterone system (RAAS) inhibitors, according to a real-world study presented at the American Society of Nephrology Kidney Week 2026 in Denver, Colorado.¹ Two additional posters at the meeting found that patients with AMKD and proteinuria experienced rapid declines in estimated glomerular filtration rate (eGFR) regardless of whether they had type 2 diabetes, including in a cohort of people living with HIV.^2,3

Together, the analyses highlight AMKD’s quick progression in routine practice despite background CKD therapy.

Real-World Treatment Patterns in AMKD

A cross-sectional treatment patterns study used Natera’s RenasightIQ Clinicogenomic Database and NorstellaLinQ Real-World Data to identify patients in the US 10 years or older with genetic confirmation of AMKD between March 2025 and February 2026.¹ Patients with evidence of diabetes, autosomal dominant polycystic kidney disease, or IgA nephropathy were excluded, leaving 1332 patients with a mean (SD) age of 45.6 (15.4) years. Just over half (54.2%) were male patients.

Hypertension (88.9%), hyperlipidemia (42.3%), and chronic pulmonary disease (23.1%) were the most common comorbidities, and 45.7% of patients were in CKD stage 4 or 5. Among the 63% of patients with eGFR values recorded during the study period, the mean (SD) eGFR was 38 (29) mL/min/1.73 m². Within the study period, 35.7% of patients had at least 1 administration or fill of a RAAS inhibitor, 35% of a calcium channel blocker, 27.9% of a beta blocker, 10.5% of an SGLT2 inhibitor, and 4.4% of a GLP-1 receptor agonist.

“Variable treatment utilization and substantial residual disease burden underscore the significant unmet need for targeted therapies that address the underlying disease pathophysiology,” the authors concluded.¹

The study was limited by its cross-sectional nature, captured only whether patients had at least 1 administration or fill of each drug class, and had eGFR values for 63% of patients.

Rapid eGFR Decline in Proteinuric AMKD, With or Without Diabetes

A natural history study from Vanderbilt University Medical Center and the VA Tennessee Valley Healthcare System included 1546 patients of African ancestry with high-risk APOL1 genotypes and a urine albumin-creatinine ratio of at least 321 mg/g (stage A3 CKD), drawn from the Million Veteran Program (MVP; n = 1265) and Vanderbilt’s BioVU biobank (n = 281).²

The authors noted that earlier longitudinal studies of proteinuric AMKD were limited by sample size and did not include patients with type 2 diabetes, who made up 65% of this cohort. The mean (SD) age was 61 (12) years, 86% of patients were male, the mean baseline eGFR was 54 (18) mL/min/1.73 m², and the mean follow-up was 3.6 (3.3) years.

Almost all subgroups, which were defined by diabetes status and baseline eGFR cutoffs, experienced eGFR decline faster than 3 mL/min per year, with faster declines in patients with diabetes. In the pooled cohort with baseline eGFR below 90 mL/min/1.73 m², the mean annual eGFR slope was –3.0 mL/min/1.73 m² (95% CI, –3.3 to –2.7) in patients without diabetes and –4.2 mL/min/1.73 m² (95% CI, –4.5 to –3.9) in patients with type 2 diabetes.

For patients with baseline eGFR below 75 mL/min, the median time to a composite of a 30% or greater eGFR decline, end-stage kidney disease, or death ranged from 3 to 5 years across subgroups. Among MVP participants with eGFR below 90 mL/min, median time to the composite was 4 years (95% CI, 1.8-8.2) without diabetes and 3.1 years (95% CI, 1.4-5.5) with diabetes.

The authors concluded that the results were independent of diabetes status. “Additional studies evaluating higher risk subgroups and incorporating genetic modifiers are needed,” they wrote.

AMKD Progression Among People Living With HIV

A third poster, from researchers at NYU Grossman School of Medicine, the University of Alabama at Birmingham, and Vertex, examined 83 people living with HIV in the CFAR Network of Integrated Clinical Systems who had high-risk APOL1 genotypes, incident proteinuria (a first urine protein-creatinine ratio of at least 0.2 g/g), and eGFR of 25 to less than 90 mL/min/1.73 m².³ Of these participants, 18 (22%) had diabetes. At proteinuria onset, participants without diabetes were younger and had lower eGFR, higher proteinuria, lower body mass index, and higher HIV viral loads.

In participants without diabetes, the modeled eGFR slope was +14.5 per year in the 6 months after proteinuria onset, then –5.3 per year thereafter.³ In participants with diabetes, the slope was –4.0 per year in the first 6 months and –6.4 per year afterward. Event-free survival 5 years after proteinuria onset was 53.8% among participants with diabetes and 70.2% among those without diabetes, a difference that was not statistically significant (P = .37).

“AMKD in [people living with HIV] is characterized by rapid kidney function decline, regardless of baseline diabetes status. This period of incident proteinuria may represent the ideal window for therapeutics aimed at halting disease progression,” the authors of the HIV cohort study concluded.

References

1. Shah A, Voegel A, Salgaonkar P, Christensen D, Clark D, Barber B. Real-world treatment patterns among patients with APOL1-mediated kidney disease (AMKD) in the United States. Poster presented at: Kidney Week 2026; October 22-25, 2026; Denver, Colorado. Abstract FR-PO0109.

2. Mamak F, Bidhan S, Yu Z, et al. Natural history study of patients with proteinuric APOL1-mediated kidney disease (AMKD) in BioVU and the Million Veteran Program (MVP). Poster presented at: Kidney Week 2026; October 22-25, 2026; Denver, Colorado. Abstract FR-PO0154.

3. Reed RD, Locke JE, Wu K, et al. APOL1-mediated kidney disease (AMKD) progression among people living with HIV. Poster presented at: Kidney Week 2026; October 22-25, 2026; Denver, Colorado. Abstract FR-PO0254.