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The role of complement in kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO)
Marina Vivarelli1, Jonathan Barratt2, Laurence H Beck3
1Laboratory of Nephrology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Insights
Uncontrolled complement activation damages kidneys in various diseases like atypical hemolytic uremic syndrome and diabetic nephropathy. New therapies and biomarkers are emerging to manage these complement-mediated kidney diseases.
Area of Science:
- Nephrology
- Immunology
- Complement System Biology
Background:
- Uncontrolled complement activation is increasingly recognized as a contributor to glomerular injury across diverse kidney diseases.
- While its role in atypical hemolytic uremic syndrome and C3 glomerulopathy is established, evidence now implicates complement in diabetic nephropathy and glomerulonephritides.
- The parallel rise in complement inhibitor therapies necessitates a comprehensive understanding of complement's role in kidney disease.
Purpose of the Study:
- To address the expanding role of complement dysregulation in kidney disease pathophysiology, diagnosis, and management.
- To review evidence for complement's causal or secondary role in disease progression.
- To identify research priorities and knowledge gaps in complement-mediated kidney diseases.
Main Methods:
- Convened a KDIGO Controversies Conference in 2022 focused on "The Role of Complement in Kidney Disease."
- Reviewed existing evidence on complement activation in glomerular diseases, diabetic nephropathy, and hemolytic uremic syndrome.
- Examined patient and caregiver perspectives on treatment, genetic testing, and therapy implementation.
- Assessed the utility of biomarkers and the influence of the glomerular microenvironment.
Main Results:
- Evidence confirms complement's significant role in the progression of multiple kidney diseases beyond traditional indications.
- Patient and caregiver concerns highlight the need for holistic management strategies, including genetic counseling and equitable access to novel therapies.
- Biomarker utility and the glomerular microenvironment's impact on complement response require further investigation.
Conclusions:
- Complement dysregulation is a critical factor in a wide spectrum of kidney diseases, necessitating targeted therapeutic approaches.
- Effective management requires integrating novel therapies, patient-centered concerns, and advanced monitoring tools.
- Further research is crucial to refine diagnostic criteria, optimize treatment strategies, and address knowledge gaps in complement-mediated kidney diseases.
Abstract:
Uncontrolled complement activation can cause or contribute to glomerular injury in multiple kidney diseases. Although complement activation plays a causal role in atypical hemolytic uremic syndrome and C3 glomerulopathy, over the past decade, a rapidly accumulating body of evidence has shown a role for complement activation in multiple other kidney diseases, including diabetic nephropathy and several glomerulonephritides. The number of available complement inhibitor therapies has also increased during the same period. In 2022, Kidney Diseases: Improving Global Outcomes (KDIGO) convened a Controversies Conference, "The Role of Complement in Kidney Disease," to address the expanding role of complement dysregulation in the pathophysiology, diagnosis, and management of various glomerular diseases, diabetic nephropathy, and other forms of hemolytic uremic syndrome. Conference participants reviewed the evidence for complement playing a primary causal or secondary role in progression for several disease states and considered how evidence of complement involvement might inform management. Participating patients with various complement-mediated diseases and caregivers described concerns related to life planning, implications surrounding genetic testing, and the need for inclusive implementation of effective novel therapies into clinical practice. The value of biomarkers in monitoring disease course and the role of the glomerular microenvironment in complement response were examined, and key gaps in knowledge and research priorities were identified.
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