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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.
Kidney International
|June 6, 2024
Summary
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.
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