# Lipidomic Predictors of Diabetic Kidney Disease Progression in Patients with Type-1 Diabetes

> **NIH NIH R03** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $81,297

## Abstract

ABSTRACT
Diabetes is the leading cause of end stage kidney disease in the United States. Currently there is no biomarker
to identify patients at high risk of progression of diabetic kidney disease (DKD) when GFR is preserved (>90
mL/min) and urine albumin excretion is within normal limit. In this study we aim to test the predictive power of
C16-C24 free fatty acids (FFA)s and C40-C46 triacylglycerols (TAG)s in plasma to predict progression of DKD
at early stage when estimated GFR (eGFR) is greater than 90 mL/min and urine albumin-creatinine ratio (ACR)
is less than 30 mg/g. This study will be a case control observation in which the case group is defined as
progression of DKD in longitudinal follow up visits. Patient population is the patients with type-1 diabetes. Study
samples are selected from 4 established cohorts of patients with type-1 diabetes including the Steno Diabetes
Center Copenhagen, the Finnish Diabetic Nephropathy (FinnDiane), the Colorado Coronary Artery Calcification
in Type 1 diabetes (CACT1), and the Pittsburgh Epidemiology of Diabetic Complications (EDC). Sampling is
based on the application of the inclusion and exclusion criteria. The inclusion criteria are age of 18 years or older
at the time of sample selection, eGFR ≥90 ml/min, ≥3 longitudinal measure of eGFR, and follow up of more than
4 years. Exclusion criterion is age<18 years. Case group is defined as patients with type-1 diabetes who had >3
ml/min/year loss in eGFR during follow up. Control group is defined as patients with type-1 diabetes who had no
or less than 1 mL/min/year loss in eGFR during follow up, frequency matched by age, sex, race, and eGFR at
baseline with the case group. Overall, 350 patients including non-progressors and progressors with a 2:1 ratio
are selected. After selection, patients will be randomly split to the training (57 progressors and 117 non-
progressors) and validation cohorts. Outcome is progression of DKD defined as >3 mL/min/year loss in eGFR
during follow up visits. Clinical data and plasma samples at baseline visit (corresponding date of matching cases
and controls) are available. Targeted lipidomic studies (based on our preliminary data) will be applied to quantify
the proposed lipids in multiple reaction monitoring (MRM) mode using an AB Sciex Triple Quadrupole/QTRAP
6500+ mass spectrometer. For analysis, we will apply t-test with false discovery rate correction for multiple
comparisons using a compound by compound comparison for ability to predict DKD progression. Additionally,
we will use principal component for data reduction, and will incorporate the significant lipids as well as the
principal components separately in adjusted logistic regression models to test the independent prediction of
proposed markers on DKD progression. We will calculate c-statistics and compare it to that of eGFR and ACR
to assess the improvement of classification power. We will replicate the analysis in the validation subset
consisting of 175 patients ...

## Key facts

- **NIH application ID:** 9968325
- **Project number:** 5R03DK121941-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Farsad Afshinnia
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $81,297
- **Award type:** 5
- **Project period:** 2019-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968325

## Citation

> US National Institutes of Health, RePORTER application 9968325, Lipidomic Predictors of Diabetic Kidney Disease Progression in Patients with Type-1 Diabetes (5R03DK121941-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9968325. Licensed CC0.

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