Kidney Week

Abstract: FR-PO0139

A Double Hit to the Podocyte: C1q Nephropathy and APOL1 High-Risk Genotype Presenting as FSGS

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

• Bowling, Carly M., Walter Reed National Military Medical Center, Bethesda, Maryland, United States

Carly M. Bowling, MD

• Silverberg, Rachael A., Walter Reed National Military Medical Center, Bethesda, Maryland, United States

Rachael A. Silverberg, MD, MPH

• Malone, Laura, Walter Reed National Military Medical Center, Bethesda, Maryland, United States

Laura Malone, MD

• Nee, Robert, Walter Reed National Military Medical Center, Bethesda, Maryland, United States

Robert Nee, MD, FASN

Introduction

Two gain-of-function mutations in the apolipoprotein 1 (APOL1) gene have been identified as a major risk factor for nondiabetic kidney disease among individuals with African ancestry. C1q nephropathy (C1qN), defined by dominant or codominant C1q staining and mesangial electron-dense deposits without evidence of systemic lupus erythematosus, is rarely associated with APOL1-mediated kidney disease (AMKD). This report describes early outcomes to treatment of C1qN in a patient with AMKD.

Case Description

A 31-year-old female from Nigeria presented with two days of bilateral pedal edema and foamy urine. Lab studies showed nephrotic-range proteinuria, hypoalbuminemia and hyperlipidemia. Her renal function was preserved with an estimated glomerular filtration rate (eGFR) 70 mL/min/1.73m². Serologic work-up for lupus, viral hepatitis, human immunodeficiency virus, anti-phospholipase A2 receptor antibody, and monoclonal gammopathies was negative. Renal biopsy demonstrated FSGS with dominant (3+) C1q and kappa mesangial staining, consistent with C1qN. Interstitial fibrosis and tubular atrophy involved 40% of the sampled cortex. Genetic testing showed homozygous risk alleles (G1/G1) for APOL1. Her proteinuria did not improve after one month of prednisone 60 mg daily as first-line therapy. She is now receiving calcineurin inhibitor and low-dose prednisone for steroid-resistant disease. Clinical results are pending.

Discussion

C1qN is a rare glomerulopathy of unclear pathophysiology. Development of C1qN in a patient with APOL1 high-risk genotype may suggest synergistic mechanisms of podocyte injury. In this context, C1qN could represent a superimposed immune-mediated process, a secondary epiphenomenon of podocyte injury, or a “second hit” modifier of disease trajectory in a genetically susceptible individual. Emerging therapies targeting APOL1-mediated pathways are promising, but their role in patients with overlapping immune complex deposition is unclear. This exceptional case underscores the interplay between C1qN and APOL1 high-risk genotype in podocyte injury leading to FSGS.

Disclaimer: The views expressed in this abstract are those of the authors and do not necessarily reflect the official policy of the Department of War or the U.S. Government.