Kidney Week

Abstract: SA-PO0703

Immunofluorescence Unmasks C3-Dominant Glomerulonephritis in an Electron Microscopy (EM)-Negative Biopsy

Session Information

• Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Ullah, Izhar, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Izhar Ullah, MD

• Khan, Asmad, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Asmad Khan, MD

• Salih, Noman, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Noman Salih, MD

• Hanif, Muhammad Owais, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Muhammad Owais Hanif, MD

• Khan, Kazi S., TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Kazi S. Khan, MD

• Arif, Ali, TidalHealth Peninsula Regional, Salisbury, Maryland, United States

Ali Arif, MD, MBBS, FASN

Introduction

C3 glomerulonephritis is an ultra-rare, complement-mediated kidney disease (1–3 cases/million/year) characterized by dominant glomerular C3 deposition and an MPGN pattern of injury. Although hypocomplementemia is common, serum C3 may be normal, and in adults ≥50 years, monoclonal gammopathy–associated complement dysregulation should be considered. Here we present a case of non-diabetic elderly female in which dominant C3 immunofluorescence was the decisive clue in clinching the diagnosis of C3GN

Case Description

A 73-year-old nondiabetic woman with CKD (creat1.76 mg/dL) hypertension and lower-extremity edema presented with nephrotic-range proteinuria 3.9 gm albuminuria and microscopic hematuria 5-10 Rbc on urinalysis; serum albumin was preserved (4.0 g/dL). Serologic evaluation was negative, including PLA2R antibody, ANA/ANCA, cryoglobulins, and hepatitis profile. Serum and urine immunofixation and free light chain testing showed no evidence of monoclonal gammopathy. Kidney biopsy (February 2026) demonstrated an MPGN pattern with mesangial and endocapillary hypercellularity, capillary wall double contours, PAS-positive mesangial nodules, and microaneurysms. Chronicity was present (7/15 globally sclerosed glomeruli; ~30% interstitial fibrosis/tubular atrophy). IF showed dominant C3 staining (3+) in the mesangium and along capillary walls with only trace IgM and negative IgG, IgA, C1q, kappa, and lambda, consistent with a C3-dominant glomerulonephritis in the C3G spectrum. EM showed moderate podocyte foot process effacement with no definite electron-dense deposits along glomerular capillary walls or tubular basement membranes; only sparse mesangial electron-dense deposits were identified, creating a clinicopathologic diagnostic dilemma.

Discussion

Supportive therapy was continued with RAASi and SGLT2 inhibitor. Targeted complement inhibition with iptacopan (oral factor B inhibitor) was discussed as a potential option based on emerging/available trial data, pending shared decision-making.This case highlights a diagnostic pitfall in which immunofluorescence demonstrated dominant C3 deposition supporting a C3-dominant process in the C3G spectrum. Normal serum C3 complement and limited/absent capillary wall deposits on EM may delay recognition of C3-dominant disease. Dominant C3 staining on IF should prompt careful exclusion of secondary causes and consideration of complement-directed evaluation and therapy.