# C3 Glomerulopathy -- A Collaborative Study

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $627,373

## Abstract

Project Summary/Abstract
 C3 glomerulopathy (C3G) is an aggressive form of glomerular disease that occurs at any age and carries
the highest risk for irreversible renal failure of the known glomerular diseases. Recurrence post-renal
transplant remains a major medical issue for the most patients. This dismal outlook reflects an incomplete
understanding of the underlying pathophysiology of C3G, a knowledge gap that has not only led to our inability
to explain the limited success of currently available anti-complement agents, but has also hindered the
development of new therapies for C3G.
 Familial cases support the hypothesis that C3G results from primary complement dysregulation however
our understanding of the genetics of C3G is incomplete. An adequate accounting for the role of
autoantibodies in C3G is also lacking. Finally, in the majority of patients, C3G follows a chronic, indolent
course. Activation of the alternative complement pathway can be documented, with kidney biopsies confirming
the deposition of complement proteins and their cleavage products in the renal glomerulus. However, the
association between complement activity and clinical outcome is poorly understood, a reflection of the
absence of longitudinal studies of C3G focused on genetics, autoantibodies, and complement activity in
relationship to long-term renal outcome.
 In this grant, we propose to:
 • Specific Aim 1. Define genetic drivers of C3G
 • Specific Aim 2. Identify and characterize autoantibodies to complement proteins and convertases
 • Specific Aim 3. Develop and validate clinically useful predictive models of disease progression in a
 longitudinal data-driven analysis of complement factors in C3G
 Completing these aims will meet our short-term goals, which are to provide a better understanding of C3G
and to improve care for C3G patients, and provide a foundation for our long-term goal, which is to identify an
effective treatment for this disease.

## Key facts

- **NIH application ID:** 9851393
- **Project number:** 5R01DK110023-04
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Patrick Breheny
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $627,373
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851393

## Citation

> US National Institutes of Health, RePORTER application 9851393, C3 Glomerulopathy -- A Collaborative Study (5R01DK110023-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851393. Licensed CC0.

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