Urine proteins may aid drug monitoring in kidney disease
A urine protein measure linked to kidney injury fell 46.3% from baseline after six weeks of atrasentan in people with chronic kidney disease.
Limit: Many urinary endothelin-1 measurements were below quantification limits, limiting detection of treatment effects
Stake: Authors take fees from AstraZeneca, which develops dapagliflozin, and receive grants from it.
Edited by Boris Djordjevic · AgingResearch.News
Researchers analyzed two randomized trial populations with chronic kidney disease. SONAR included 308 people averaging 65 years old; 25% were women, and all had type 2 diabetes. They received atrasentan, 0.75 mg daily, for six weeks before randomization. Urinary clusterin, a protein linked to injury in the kidney’s tiny tubes, fell 46.3% from baseline.
DAPA-CKD included 2,450 people averaging 62 years old; 33% were women and 69% had type 2 diabetes. Participants received dapagliflozin, 10 mg daily, or placebo. Among 2,303 with one-year samples, dapagliflozin slowed the decline in urinary epidermal growth factor, a protein linked to repair in those tubes, by 9.7% relative to placebo. Both protein measures accounted for urine concentration. Responses to dapagliflozin varied by kidney disease cause and were larger with type 2 diabetes and higher starting blood sugar.
Why it matters
For older adults with chronic kidney disease, this work addresses whether urine tests can capture distinct biological responses to drugs beyond those reflected by the usual urine albumin measure.
Caveats
The atrasentan analysis had no placebo comparison, and neither analysis tested whether using these markers improved care. Both used selected participants with available samples; the findings do not address people without chronic kidney disease.
From the paper
- Who took part
We included participants from the SONAR and the DAPA-CKD trials.
- Analyzed for uCLU/Cr
Among the 5117 participants in the SONAR trial, we included 308 (6%) from the enrichment phase with available serum and urine samples at baseline and after 6 weeks of treatment with atrasentan.
- Analyzed for uEGF/Cr decline
Among 4304 participants in DAPA-CKD, we included 2450 (57%) with available urine samples at baseline, of whom 2303 (94%) also had samples available at year 1.
- Follow-up
The median follow-up was 2.2 years and the primary endpoint was a composite of sustained doubling of serum creatinine, kidney failure, or kidney-related death.
- Result
The geometric mean sET-1 increased from 3.74 pg/ml (95% CI 3.60–3.89) at baseline to 4.77 pg/ml (95% CI 4.62–4.93) at week 6, corresponding to a median increase of 23.4% (95% CI 19.2–27.4).
- UCLU/Cr
The geometric mean urinary clusterin-to-creatinine ratio (uCLU/Cr) decreased from 0.44 mg/g (95% confidence interval [CI] 0.38–0.50) at baseline to 0.26 mg/g (95% CI 0.22–0.30) at week 6, corresponding to a median decrease of 46.3% (95% CI −57.8 to −37.1).
- UEGF/Cr decline
After 1 year of treatment, dapagliflozin attenuated the decline in uEGF/Cr compared with placebo by 9.7% (95% CI 5.0–14.3) in the overall population.
Quoted word for word from the full text on PubMed Central.
The paper
Novel protein biomarkers for risk stratification and personalized medicine
University Medical Center Groningen
Nephrology, Dialysis, Transplantation, Mar 24, 2026, Open access
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