# Project 4: Protecting Renal functiOn with Urate-lowering Drugs (PROUD)

> **NIH NIH P50** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $199,044

## Abstract

PROJECT SUMMARY 
The management of gout is suboptimal and complicated by high prevalence of comorbidities, including chronic 
kidney disease (CKD); 71% of gout patients in U.S. have CKD stage 2 or higher. A key reason for 
suboptimal gout care is lack of knowledge and acceptance for the utility of lowering serum urate (sUA) levels to 
< 6 mg/dl (based on the solubility threshold of 6.8 mg/dl), known as treat-to-target (TTT). While a sUA 
threshold of < 6 mg/dl is valuable for managing gout, it has not been examined for renal function preservation. 
Recently, the Department of Veterans Affairs (VA) funded a 4-year randomized, double-blinded, non-inferiority 
“Stop Gout” (VA CSP594) study with a sUA TTT approach, which will assess the comparative effectiveness of 
allopurinol vs. febuxostat. Our proposed study, Protecting Renal functiOn with Urate-lowering Drugs (PROUD), 
a mechanistic ancillary study to this innovative trial, will leverage trial data to assess whether achieving target 
sUA is valuable for renal function preservation for the first time, with the following two specific aims. 
Specific Aim 1 is to evaluate the efficacy of sUA lowering and allopurinol and febuxostat dose in 
preserving renal function in gout patients. We hypothesize that each of the following factors will be 
positively associated with renal function preservation as assessed by change in eGFR based on serum 
creatinine at 72-weeks (primary outcome) and serum Cystatin C at 48-weeks (secondary outcome): Achieving 
a sUA reduction and a target sUA level < 6 mg/dl at 24-weeks (Hypotheses 1a and 1b), baseline CKD Stage 3 
(compared to CKD stage 1 or 2; Hypothesis 1c), the final up-titrated allopurinol dose at 21-weeks (Hypothesis 
1d), and the final up-titrated febuxostat dose at 18-weeks (Hypothesis 1e). Specific Aim 2 will assess the 
mechanisms of renal function preservation in gout. We hypothesize that reduction at 24-weeks in each of 
the following will be associated with renal function preservation at 72-weeks: Renin-angiotensin system 
activation (plasma renin and aldosterone; Hypothesis 2a), systemic inflammation (IL-1β, IL-6, TNF-α, MCP-1, 
PDGF, C-reactive protein; Hypothesis 2b), and oxidative stress level (lipid peroxidation by 8-epi-PGF2a; 
protein oxidation by carbonyl formation, 3-nitrotyrosine formation and reduced thiol status; Hypothesis 2c). 
PROUD will have high public health impact and will advance the field by addressing unanswered questions 
related to renal function preservation with XOI in gout and underlying mechanisms. The University of Alabama 
at Birmingham (UAB) and the University of Nebraska Medical Center (UNMC), two large academic gout and 
immunology research centers, are ideally positioned to address the clinical and mechanistic questions posed. 
Our collaborative expertise, complemented by the leveraged resources of the proposed NIAMS supported P50 
UAB Center of Research Translation (CORT) will be used to execute this novel translationa...

## Key facts

- **NIH application ID:** 10017010
- **Project number:** 5P50AR060772-09
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Jasvinder Singh
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,044
- **Award type:** 5
- **Project period:** 2012-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017010

## Citation

> US National Institutes of Health, RePORTER application 10017010, Project 4: Protecting Renal functiOn with Urate-lowering Drugs (PROUD) (5P50AR060772-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10017010. Licensed CC0.

---

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