# Understanding the role of the Complement Proteome in progressive Diabetic Kidney Disease

> **NIH NIH R01** · JOSLIN DIABETES CENTER · 2022 · $516,658

## Abstract

PROJECT SUMMARY / ABSTRACT
There is a critical need to identify novel mechanisms of diabetic kidney disease (DKD) that will provide targets
for new interventions. Chronic inflammation is one plausible mechanism.
Using untargeted high-throughput aptamer proteomics, our recently published study has shed new light on
specific, key inflammatory drivers of DKD. This was a large prospective three-cohort study that identified a
novel and extremely robust circulating signature (KRIS) associated with risk of ESRD in diabetes.
Our pilot study points to the data-driven connection between circulating KRIS and urinary profiles of the
Complement pathway. Our hypothesis is that the Complement involvement in the kidney is a downstream
effect of the systemic inflammatory processes mediating an increased DKD risk.
The overarching goal of this proposal is to provide a high-resolution view of the involvement of the
Complement proteome in progressive diabetic kidney disease.
Aim 1 will comprehensively evaluate the etiological role of the urinary Complement proteome in progressive
DKD leading to ESRD. This evaluation will leverage a prospective two-cohort population of Joslin Kidney Study
(JKS) participants with an overt DKD at baseline followed for 10 years (primary outcome – incident ESRD).
Measurements will utilize an aptamer proteomic technology (SOMAscan).
Aim 2 will extend generalizability of the urinary Complement proteome to earlier DKD stages. The proposed
study will be conducted in participants of the Preventing Early Renal Loss (PERL) clinical trial with
predominantly normal renal function at baseline followed for 3 years (primary outcome - renal slope).
Aim 3 proposes to gain direct insight into the intra-renal Complement proteome by targeted and untargeted
protein studies in diabetic kidney tissue (Susztaklab Biobank).
This project focuses on a significant public health problem, leverages the progressiveness of the disease,
employs an innovative proteomic technology and stems from strong preliminary data. Advances in this project
will pinpoint missing key components of DKD etiology, thereby accelerating drug development strategies for
patients with diabetes.

## Key facts

- **NIH application ID:** 10370409
- **Project number:** 5R01DK123459-03
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** Monika Anna Niewczas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $516,658
- **Award type:** 5
- **Project period:** 2020-04-30 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370409

## Citation

> US National Institutes of Health, RePORTER application 10370409, Understanding the role of the Complement Proteome in progressive Diabetic Kidney Disease (5R01DK123459-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10370409. Licensed CC0.

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