# Biomarkers for acute interstitial nephritis in humans

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $610,901

## Abstract

SUMMARY
Acute interstitial nephritis (AIN) results from an immune-mediated kidney injury, which is triggered by use of
medications (such as proton pump inhibitors, antibiotics, and immune checkpoint inhibitors) or by autoimmune
diseases (such as Sjogren’s syndrome and sarcoidosis). An episode of AIN results in permanent kidney
damage in 40-60% of patients and AIN is the cause of about 2% of all cases of chronic kidney disease, which
is equivalent to 0.5-1 million U.S. adults. There are two major challenges in the clinical care of patients with
AIN. First, due to lack of a reliable non-invasive biomarker, AIN diagnosis requires a kidney biopsy. Biopsy
may not be feasible in some patients due to bleeding risk or is delayed in order to optimize this risk. This delay
in diagnosis contributes to incomplete recovery of kidney function. Second, corticosteroid therapy, the current
standard of care for AIN treatment, does not appear to benefit all patients while exposing them to the risk of
short- and long-term adverse events. However, characteristics predicting a favorable response to corticosteroid
therapy are currently unknown.
The overall goal of this proposal is to validate urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α as
biomarkers to diagnose AIN (aim 1) and to identify the subgroup of patients in whom corticosteroid therapy is
beneficial (aim 2). In a study of 265 patients conducted at two Yale-affiliate hospitals, we showed that the
multiplication product of IL-9 and TNF-α (IL-9*TNF-α) was independently associated with AIN and showed area
under receiver operating characteristic curve [AUC] of 0.79 (95% CI, 0.71, 0.88). Addition of IL-9*TNF-α to the
clinician’s pre-biopsy diagnosis increased AUC from 0.62 (0.53, 0.71) to 0.85 (0.78, 0.91). We also found that
corticosteroid use was associated with higher glomerular filtration rate 6-months after diagnosis only in patients
with higher urine IL-9*TNF-α (by 19.7 ml/min/1.73m2). Here we propose a larger, multicenter, observational
study to validate these findings. We will enroll a cohort of 580 patients at two large university medical centers
(Yale and Johns Hopkins), collect urine samples for biomarker measurement, and establish presence or
absence of AIN through an independent, blinded adjudication process led by three renal pathologists. In aim 1,
we will validate IL-9*TNF-α as a diagnostic biomarker for AIN by demonstrating improvement in AUC for AIN
with IL-9*TNF-α over a clinical model and clinician’s prebiopsy impression. We will also describe test
characteristics at two pre-specified cut-offs and test accuracy in differentiating key sub-groups (drug vs. other
and by drug classes). In aim 2, we will validate IL-9*TNF-α as a biomarker to identify subgroup of patients most
likely to experience kidney function recovery with clinically-prescribed corticosteroids. We will follow patients
with AIN for up to six months to determine kidney function after AIN. Results from this study will al...

## Key facts

- **NIH application ID:** 10402806
- **Project number:** 5R01DK128087-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Dennis G. Moledina
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $610,901
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402806

## Citation

> US National Institutes of Health, RePORTER application 10402806, Biomarkers for acute interstitial nephritis in humans (5R01DK128087-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10402806. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*