Abstract: PUB215
Hematuria and Proteinuria in a Patient of Cypriot Descent
Session Information
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Liang, Kelly V., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
- Ellis, Brigid K., Tower Health, Reading, Pennsylvania, United States
- Stokes, Michael Barry, Columbia University Irving Medical Center, New York, New York, United States
- Smith, Richard J., The University of Iowa Hospitals and Clinics Department of Pathology, Iowa City, Iowa, United States
- Gale, Daniel P., University College London, London, London, United Kingdom
Introduction
C3 glomerulonephritis (C3GN) caused by a mutation in complement Factor H-related protein 5 (CFHR5) is endemic in patients of Cypriot descent. CFHR5 nephropathy bears a striking resemblance to IgA nephropathy (IgAN). We present a case of CFHR5 nephropathy in a Cypriot patient who was initially diagnosed with IgAN and highlight the importance of family history, labs, renal biopsy, and genetic testing in diagnosis of CFHR5 nephropathy.
Case Description
A 22-year-old male of Cypriot and Greek descent presented in June 2019 with recurrent microscopic hematuria and proteinuria in the setting of upper respiratory tract and gastrointestinal illness. Blood pressure was 132/78 and he had no edema. Serum creatinine (SCr) was 1.6 mg/dL (SCr was 0.7 in 2012, 1.0 in 2018, and 1.3 in 2019). Urinalysis revealed microscopic hematuria and proteinuria. Spot urine protein/Cr ratio (UPCR) was 580 mg/g Cr. Serologic workup was unremarkable. He was diagnosed initially with IgA nephropathy. Due to slowly progressive renal dysfunction, a renal biopsy was performed in January 2020, which showed mild mesangial hypercellularity, segmental duplication of basement membranes, and glomerular C3 deposits. Immunofluorescence was negative for IgG, IgM, C1q, light chains, or fibrin. Electron microscopy revealed segmental mesangial, subepithelial, and subendothelial immune-type electron dense deposits with segmental duplication of glomerular basement membranes. He was diagnosed with C3GN. Genetic testing confirmed the CFHR5-CFHR5 fusion gene that has been causally linked to C3GN by a gain-of-function effect leading to overactivation of the alternative complement pathway. He was treated conservatively with Lisinopril 10 mg daily. Home blood pressures remain stable. SCr remains 1.5 to 1.9 mg/dL and UPCR remains 610 to 810 mg/g Cr.
Discussion
CFHR5 nephropathy is endemic in patients of Cypriot descent. Therefore, a high index of suspicion for CFHR5 nephropathy should be maintained in Cypriot patients presenting with nephritic syndrome. The presentation of CFHR5 nephropathy bears a striking similarity to IgAN. The main distinguishing features of CFHR5 nephropathy vs. IgAN are its familial nature and absence of IgA deposition. Therefore, family history, renal biopsy, and genetic testing for CFHR5 mutation are critical in establishing a diagnosis of CFHR5 nephropathy.
