# Clinical applications of urine proteomics to lupus nephritis

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $665,224

## Abstract

Abstract
Lupus nephritis (LN) is diagnosed by kidney biopsy in patients with proteinuria > 0.5g/24h, but the
presence of proteinuria means that kidney damage has already occurred. It is estimated that 30% of
nephrons are permanently lost with each flare of LN. The identification of LN before kidney damage
using urine proteomic biomarkers could shift the management strategy of LN to prevention,
potentially leading to earlier, more effective, and less toxic treatment. Three specific aims will be
addressed in this R01 building on the work of the Hopkins Lupus Cohort (a 35 year, 2855 SLE
longitudinal cohort in which patients are followed by protocol every 3 months) and in particular on the
urine biomarker discoveries from the NIH RA/SLE Accelerated Medicines Partnership (AMP).
Aim 1 - Develop a urine biomarker panel to identify new lupus nephritis BEFORE proteinuria.
Previous AMP urine proteomic studies revealed that urinary IL-16, CD163, and neutrophil granule
content indicate intrarenal LN activity. These biomarkers will be quantitated in urine samples collected
within 3 months before the onset of proteinuria in lupus patients who ultimately were diagnosed with
LN by renal biopsy to determine if the biomarkers are elevated compared to patients who do not
develop LN. A full urine proteomic profile will also be assessed to discover additional biomarkers that
could contribute to a robust panel for predicting onset of LN before proteinuria.
Aim 2 - Develop a urine biomarker panel to guide tapering of immunosuppression in treated
LN patients. Patients with a histological NIH activity index >2 on repeat biopsy developed a
proteinuria flare and increased mortality upon tapering of immunosuppression in one study. Four
urinary biomarkers associated with NIH activity index >2 in AMP (IL-16, CD163, Galectin-1, and
PRTN3) will be quantitated ( with analysis of 1200 additional urine proteins) in urine samples from 12
LN patients in apparent clinical remission who flared upon tapering immunosuppression versus 12 LN
patients who did not flare upon tapering. The most predictive biomarkers will be combined into a 10-
plex panel to be validated in a prospective cohort of 60 patients tapering immunosuppression.
Aim 3 - Develop a biomarker for detection of early chronic kidney disease (CKD) in LN. Urine
proteomic studies on 187 patients enrolled in AMP identified TGF-β-mediated fibrosis and TNF
signaling related proteins that may be superior to proteinuria alone in detecting early CKD. These
AMP patients will be followed clinically for at least five years to determine the trajectory of their kidney
disease and to find differences in urine proteomic (and other omic) profiles between those who
maintain stable renal function versus those who do not.

## Key facts

- **NIH application ID:** 10791795
- **Project number:** 5R01DK134625-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Andrea Fava
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $665,224
- **Award type:** 5
- **Project period:** 2023-03-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10791795

## Citation

> US National Institutes of Health, RePORTER application 10791795, Clinical applications of urine proteomics to lupus nephritis (5R01DK134625-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10791795. Licensed CC0.

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