Study Finds Biomarkers That May Help Predict, Manage Chronic Kidney Disease

Key Takeaways

Novel biomarkers demonstrated comparable predictive power to established risk factors for kidney failure and all-cause mortality in CKD patients.
The NURTuRE-CKD study evaluated 21 biomarkers linked to kidney damage, fibrosis, inflammation, and cardiovascular disease.
Established risk factors slightly outperformed biomarker models for kidney failure, but both models showed equivalent discrimination for all-cause mortality.
Biomarkers have the potential to enhance personalized CKD therapy, though limitations exist, such as lack of cardiovascular event data and generalizability to diverse populations.

New research reveals that novel biomarkers enhance risk prediction for kidney failure and mortality in chronic kidney disease (CKD), paving the way for personalized treatment.

New data published in the Journal of the American Society of Nephrology show that risk prediction models that incorporate novel biomarkers demonstrated comparable discrimination to the established risk factors of kidney failure and all-cause mortality in patients with chronic kidney disease (CKD). Specifically, the study examined 21 biomarkers that are linked to kidney damage, fibrosis, inflammation, and cardiovascular disease; the authors expressed their optimism that, if confirmed in other populations, such biomarkers can help personalize CKD therapy for the individual patient.¹

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About the Trial

Trial Name: National Unified Renal Translation Research Enterprise - Chronic Kidney Disease (NURTuRE-CKD)

ClinicalTrials.gov ID: NCT04084145

Sponsor: University of Nottingham

Completion Date (Estimated): December 31, 2032

CKD, according to the study authors, is an independent risk factor of kidney failure, cardiovascular events, and higher all-cause mortality. Although the link between CKD and these outcomes is well-established, the level of risk can vary significantly between individuals, underscoring a great need to identify methods of assessing these to strengthen personalized care for the individual patient. For this reason, the current authors conducted the National Unified Renal Translational Research Enterprise (NURTuRE)–CKD study (NCT04084145) to validate biomarkers that were previously assessed in large cohorts as well as explore the potential of these novel biomarkers and their links to adverse outcomes in smaller studies.^1,2

The ongoing, prospective, multicenter, cohort study enrolled 2996 adult patients (mean age: 63 years) with an estimated glomerular filtration rate (eGFR) of 15 to 59 ml/min/1.73 m², or eGFR 60 ml/min or greater per 1.73 m², and urinary albumin creatinine ratio (UACR) greater than 300 mg/g, from 16 secondary care nephrology centers. Additionally, 86 adult controls without CKD—23 of whom had diabetes, and 63 did not—were also enrolled. Recruitment was completed between 2017 and 2019, and participants attended 1 follow-up visit, during which questionnaires were completed, and additional blood and urine samples were collected.^1,2

For the NURTuRE–CKD study, the following biomarkers were associated with 3 important broad mechanisms of CKD progression and/or premature death: kidney damage and/or fibrosis, inflammation, and cardiovascular disease.^1,2

Most of the participants were male (58%) and White (87%). Additionally, the median eGFR and UACR were 35 ml/min/1.73 m² and 197 mg/g, respectively. During a median follow-up of about 48 months, 680 kidney failure events and 414 all-cause mortality events occurred.¹

For kidney failure, a model combining 3 biomarkers (soluble TNF receptor 1, soluble cluster of differentiation 40, and urinary collagen type 1 α1 chain) showed good discrimination (C-index: 0.86 [95% CI 0.83–0.89]) but was outperformed by a model using established risk factors, including age, sex, ethnicity, eGFR, and UACR (C-index: 0.90 [95% CI 0.88–0.92]). For all-cause mortality, a model using 3 biomarkers (high-sensitivity cardiac troponin T, N-terminal pro-brain natriuretic peptide, and soluble urokinase plasminogen activator receptor) demonstrated equivalent discrimination (C-index: 0.80 [95% CI, 0.75–0.84]) to an established risk factor model (C-index 0.80 [95% CI 0.76–0.84]). Further, for the composite outcome, the biomarker model discrimination (C-index: 0.78 [95% CI 0.76–0.81]) was numerically higher than for established risk factors (C-index: 0.77 [95% CI 0.74–0.80]). The authors wrote that the addition of biomarkers to the established risk factors led to a small—but statistically significant—improvement in discrimination (C-index: 0.80 [95% CI 0.77–0.82]; P < .01).¹

"Our research shows that these novel biomarker models offer predictive results comparable to established methods, but the key finding here is that we can use these biomarkers to understand the underlying mechanisms of disease progression, potentially paving the way to more personalised treatments and medicines for CKD patients,” Tony Onoja, PhD, MSc, BSc, lead author of the study and research fellow at the University of Surrey, said in a news release.³

Despite these promising findings, the authors acknowledged that there were some limitations to the study. For example, the data on cardiovascular events and cause of death are not currently available. Additionally, the findings may not be generalizable to populations that differ from the enrolled cohort, such as those with early stages of CKD, patients in a primary care setting (rather than a health system or hospital), and patients with different racial and/or ethnic backgrounds. The investigators also acknowledged that the biomarker values were not observed to be disaggregated by sex, which is significant given the established sex-based differences in biomarker distribution and CKD outcomes; therefore, additional research must specifically include and address sex-stratified analyses.¹

"Our study demonstrates that specific biomarkers can offer a more nuanced understanding of a patient's disease progression and mortality risk and the disease’s ongoing activity. Further research is needed to evaluate how these biomarkers change in response to current treatments, and their clinical utility in patient care and in personalised medicine,” concluded Nophar Geifman, senior author of the study and professor of health and biomedical informatics at the University of Surrey.³

REFERENCES

1. Onoja A, McDonnell T, Annessi I, et al. Biomarkers of Kidney Failure and All-Cause Mortality in CKD. J Am Soc Nephrol. Published on 2025, June 20. doi:10.1681/ASN.0000000767

2. National Unified Renal Translation Research Enterprise - Chronic Kidney Disease (NURTuRE-CKD). ClinicalTrials.gov identifier: NCT04084145. Updated April 3, 2025. Accessed August 12, 2025. https://www.clinicaltrials.gov/study/NCT04084145

3. University of Surrey. Personalized chronic kidney disease management on the horizon, as new biomarker research spurs hope. News release. August 12, 2025. Accessed August 12, 2025. https://www.eurekalert.org/news-releases/1094381

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