C3 GLOMERULONEPHRITIS: UNIQUE PRESENTATION AND ROLE OF GENETIC TESTING - NEW WINE IN A NEW BOTTLE

Introduction:

43-year-old Indian woman hospitalized with acute kidney injury. 20 years prior to her current presentation, she was presumed to have IgA nephropathy when she experienced gross hematuria. At the time, she did not undergo a kidney biopsy. She was treated with fish oil supplementation, her hematuria resolved, and she was reassured that her kidney function was normal. She was then lost to follow-up locally. She relocated to the United States a year prior to the hospitalization, when she was noted to have normal kidney function as a part of her immigration paperwork. She developed an episode of sore throat 4 months prior to admission for which she was treated with antibiotics. Subsequently, she developed progressive lower extremity edema, fatigue, blurry vision, and worsening hypertension during the evaluation of which she was found to have acute kidney injury with a serum creatinine of 5.8 mg/dL and 7 g/d proteinuria. She denied skin rash, tick bites or joint pains and denied NSAID use.

Methods:

Her ultrasound was consistent with medical renal disease. Paraproteinemia screen was unremarkable. IgA levels were normal but C3 levels were low at 69. Renal biopsy showed advanced C3 glomerulonephritis (C3GN) with global and segmental glomerulosclerosis. She was noted to have severe interstitial fibrosis and tubular atrophy. There was no mesangial matrix expansion, hypercellularity or crescent formation. Immunofluorescence staining was 3+ positive for C3 only in the glomerulus and all other stains were negative. Genetic study showed a heterozygous pathogenic variant in the CFH gene with susceptibility to C3GN. 

Results:

She was started on peritoneal dialysis and has been doing very well, actively wait-listed for a kidney transplant. Transplant center is aware of her genetic study and will consider eculizumab to prevent recurrence in the allograft.C3 glomerulopathy (C3G) is a rare set of kidney diseases with 2 patterns: C3GN and dense deposit disease. Pathogenesis of both is due to complement dysregulation in the alternative pathway. Acquired or genetic alterations of the regulatory proteins of the complement pathway result in C3G. Other disease entities such as infection-related glomerulonephritis and masked monoclonal deposits can present similarly. Both the C3GN and dense deposit disease variants of C3G are progressive and recur in transplanted kidneys.

Conclusions:

This patient’s presentation has several unique features. She likely had an underlying C3GN years ago but was never biopsied. Subsequently, it appears to have been triggered by an upper respiratory infection prior to her hospitalization leading to a severe kidney injury resulting in ESRD. She also had a positive heterozygous mutation for CFH which is rare in Indian patients (Kumar, Outcome of C3 glomerulopathy patients: largest single-center experience from South Asia, 2020). This case illustrates the importance of obtaining definitive diagnosis with a biopsy, particularly in young patients as well as the importance of genetic testing which may help with planning to prevent recurrence in an allograft. While there is no definitive treatment now, these patients may benefit from immunosuppression or enrollment in clinical trials. Finally, there is limited data on ESRD modalities in C3GN; our patient has remained relatively healthy with a good quality of life on peritoneal dialysis despite her underlying kidney disease.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.