Aishwarya Ravindran1, Fernando C Fervenza2, Richard J H Smith3, An S De Vriese4, Sanjeev Sethi5. 1. Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. 2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. 3. Molecular Otolaryngology and Renal Research Laboratories, Division of Nephrology, Department of Internal Medicine, Carver College of Medicine, Iowa City, IA; Department of Pediatrics, Carver College of Medicine, Iowa City, IA. 4. Division of Nephrology, Department of Internal Medicine, AZ Sint-Jan Brugge-Oostende, Brugge, and Ghent University, Ghent, Belgium. 5. Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. Electronic address: sethi.sanjeev@mayo.edu.
Abstract
OBJECTIVE: To describe the clinicopathological features, complement abnormalities, triggers, treatment, and outcomes of C3 glomerulopathy. PATIENTS AND METHODS: A total of 114 patients with C3 glomerulopathy seen at Mayo Clinic from January 1, 2007, through December 31, 2016, were evaluated in this study. RESULTS: The mean age at diagnosis for the entire cohort was 40.4±22.3 years, with a median serum creatinine level and proteinuria value of 1.6 mg/dL (range: 0.3-14.7) (to convert to mmol/L, multiply by 0.0259) and 2605 mg/24 h (range: 233-24,165), respectively. Hematuria was present in 100 patients (87.7%). The C3 and C4 levels were low in 50 of 112 (44.6%) and 13 of 110 (11.8%) patients, respectively. A history of infection, positive autoimmune findings, and monoclonal gammopathy (MIg) were present in 33 of 114 (28.9%), 28 of 114 (24.6%), and 36 of 95 (37.9%) patients, respectively. However, 28 of 43 patients 50 years or older (65.1%) had MIg. A genetic variant in complement genes, C3 nephritic factor (C3Nef), and other autoantibodies was present in 26 of 70 (37.1%), 30 of 69 (43.5%), and 9 of 67 (13.4%) patients, respectively. Membranoproliferative and mesangial proliferative glomerulonephritis were the common patterns of injury. Patients without MIg were younger (mean age, 32.3±20.6 years), with a median serum creatinine level and proteinuria value of 1.4 mg/dL (range: 0.3-7.9) and 2450 mg/24 h (range: 250-24, 165) and with low C3 and C4 levels in 38 of 77 (49.4%) and 9 of 75 (12.0%) patients, respectively. Most patients received corticosteroids and other immunosuppressive drugs. In patients without MIg, at a median follow-up of 22.3 months (range: 0.1-201.1), the median serum creatinine level and proteinuria value were 1.4 mg/dL (range: 0.3-3.7) and 825.5 mg/24 h (range: 76-22, 603), and 7 patients (9.2%) had progression to end-stage renal disease. CONCLUSION: C3 glomerulopathy is a heterogeneous disease entity with complex triggering events and abnormalities of the alternative pathway of complement. The disease tends to be progressive and exhibits a variable response to immunosuppressive therapy.
OBJECTIVE: To describe the clinicopathological features, complement abnormalities, triggers, treatment, and outcomes of C3 glomerulopathy. PATIENTS AND METHODS: A total of 114 patients with C3 glomerulopathy seen at Mayo Clinic from January 1, 2007, through December 31, 2016, were evaluated in this study. RESULTS: The mean age at diagnosis for the entire cohort was 40.4±22.3 years, with a median serum creatinine level and proteinuria value of 1.6 mg/dL (range: 0.3-14.7) (to convert to mmol/L, multiply by 0.0259) and 2605 mg/24 h (range: 233-24,165), respectively. Hematuria was present in 100 patients (87.7%). The C3 and C4 levels were low in 50 of 112 (44.6%) and 13 of 110 (11.8%) patients, respectively. A history of infection, positive autoimmune findings, and monoclonal gammopathy (MIg) were present in 33 of 114 (28.9%), 28 of 114 (24.6%), and 36 of 95 (37.9%) patients, respectively. However, 28 of 43 patients 50 years or older (65.1%) had MIg. A genetic variant in complement genes, C3 nephritic factor (C3Nef), and other autoantibodies was present in 26 of 70 (37.1%), 30 of 69 (43.5%), and 9 of 67 (13.4%) patients, respectively. Membranoproliferative and mesangial proliferative glomerulonephritis were the common patterns of injury. Patients without MIg were younger (mean age, 32.3±20.6 years), with a median serum creatinine level and proteinuria value of 1.4 mg/dL (range: 0.3-7.9) and 2450 mg/24 h (range: 250-24, 165) and with low C3 and C4 levels in 38 of 77 (49.4%) and 9 of 75 (12.0%) patients, respectively. Most patients received corticosteroids and other immunosuppressive drugs. In patients without MIg, at a median follow-up of 22.3 months (range: 0.1-201.1), the median serum creatinine level and proteinuria value were 1.4 mg/dL (range: 0.3-3.7) and 825.5 mg/24 h (range: 76-22, 603), and 7 patients (9.2%) had progression to end-stage renal disease. CONCLUSION:C3 glomerulopathy is a heterogeneous disease entity with complex triggering events and abnormalities of the alternative pathway of complement. The disease tends to be progressive and exhibits a variable response to immunosuppressive therapy.
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