Establishing the Future Direction of Clinical Outcomes in C3 Glomerulopathy: Perspectives From a Patient and a Physician

Abstract

Complement 3 glomerulopathy (C3G) is an ultra-rare glomerulonephritis caused by dysregulation of the alternative complement pathway. C3G has an estimated incidence of 1-3 cases per million people in the United States. Diagnosing C3G based solely on clinical and laboratory features is challenging because it mimics several other glomerular diseases; therefore, diagnosis requires a kidney biopsy. In the absence of disease-modifying therapies and optimal patient management strategies, C3G poses a significant physical and emotional burden on patients and caregivers. Common symptoms of glomerulonephritis include fatigue, edema, anxiety, and/or depression, which have profound effects on patients' daily lives. Approximately half of all patients progress to kidney failure within 10 years of diagnosis. Encouragingly, the treatment landscape in C3G is poised to change, with several targeted complement inhibitors in late-stage development. This perspectives article explores a patient's journey in C3G and discusses the current and future status of clinical outcomes and patient management from the viewpoints of a practicing nephrologist and a patient.

Keywords: C3 glomerulopathy; complement-mediated kidney disease; patient; perspective; treatment outcomes.

Figure 1

The diagnostic workflow in C3G. Abbreviations: AP50, alternative pathway activation 50%; C3G, complement 3 glomerulopathy; CH50, complement hemolytic activity 50%; dsDNA, double-stranded deoxyribonucleic acid; FB, factor B; FH, factor H; FI, factor I; MCP, membrane complement protein; SPEP, serum protein electrophoresis; UPEP, urine protein electrophoresis.

Figure 2

A patient’s perspective on the C3G journey. Abbreviation: C3G, C3 glomerulopathy.

Figure 3

Key measurements and clinical outcomes in C3G. Abbreviations: AE, adverse event; AP50, alternative pathway activation 50%; C3, complement component 3; C3G, complement 3 glomerulopathy; C3G-HI, C3G-Histologic Index; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; EQ-5D-5L, EuroQol-5 Dimension-5 Level; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy – Fatigue Scale; PGIS, Patient Global Impression of Severity; QOL, quality of life; SF-36, 36-Item Short Form Health Survey; UPCR, urine protein:creatinine ratio.