# Development of Prognostic Algorithms to Identify Subjects at High Risk of ESKD in Type 2 Diabetes

> **NIH NIH R01** · JOSLIN DIABETES CENTER · 2024 · $513,666

## Abstract

PROJECT SUMMARY/ABSTRACT
With the rising prevalence of diabetes in the US and other countries, there is an ongoing research effort to find
biomarkers allowing the identification of patients with diabetes at high risk of end stage kidney disease
(ESKD). With support from NIH and JDRF, we have identified 21 serum proteins that were significantly
associated with increased risk of kidney function loss and ESKD in the Joslin Kidney Study, and have
developed an ad hoc OLINK multiplex assay (so called Joslin Kidney Panel [JKP]) to measure these
biomarkers. Preliminary data strongly suggest that a subset of the JKP can significantly improve the ability to
predict ESKD risk in subjects with type 2 diabetes (T2D) when added to GFR and allbuminuria. In this
proposal, we aim to validate these preliminary findings in other settings, in order to develop improved
algorithms for ESKD risk prediction. We intend to accomplish these goals using existing data and specimens
from individuals with and without T2D from 1. the Chronic Renal Insufficiency Cohort (CRIC) Study; and 2. the
Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and its follow-up study ACCORDION. Our
Specific Aims are: 1: To identify the most informative of the 21 biomarkers in the Joslin Kidney Panel
and evaluate their performance, when added to GFR and albuminuria, in predicting ESKD risk among
subjects with T2D and chronic kidney disease. We will measure the 21 proteins of the JKP in baseline
serum specimens from ~1,500 CRIC participants with T2D, and will use these data together with GFR and
albuminuria to develop and internally validate multi-marker prognostic algorithms predicting the risk of ESKD
(primary outcome) or the composite of ESKD and/or 50% loss of kidney function (secondary outcome) during
10 years of follow-up. 2: To evaluate the generalizability of findings from CRIC to T2D individuals with a
broader spectrum of kidney function. We will assay the JKP in baseline serum specimens from a case-
cohort sample of ~2,000 ACCORD/ACCORDION participants and will use these data to investigate the
generalizability of the predictive algorithms built in CRIC to diabetic patients with different characteristics. The
prognostic models developed in Aim 1 and externally validated in Aim 2 will be used to build a web-based
Kidney Risk Calculator for the estimation of the 10-year risk of ESKD in a clinical setting. 3: To evaluate the
transferability of the Kidney Risk Calculator from diabetic to non-diabetic kidney disease. We will
measure the 21 JKP biomarkers in baseline serum samples from ~1,700 non-diabetic subjects from the CRIC
study and will assess the performance of the Kidney Risk Calculator developed in Aim 2 in predicting the risk
of ESKD and ESKD/50% kidney function loss in patients with non-diabetic kidney disease. The proposed
research has a high likelihood of resulting in the development of improved prognostic tools for the stratification
of patients with diabetes accord...

## Key facts

- **NIH application ID:** 10911168
- **Project number:** 5R01DK126799-04
- **Recipient organization:** JOSLIN DIABETES CENTER
- **Principal Investigator:** Andrzej S Krolewski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $513,666
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911168

## Citation

> US National Institutes of Health, RePORTER application 10911168, Development of Prognostic Algorithms to Identify Subjects at High Risk of ESKD in Type 2 Diabetes (5R01DK126799-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10911168. Licensed CC0.

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