Related Experiment Video
Updated: Jul 13, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Plasma Biomarkers and Incident CKD Among Individuals Without Diabetes
Dustin Le1, Jingsha Chen2, Michael G Shlipak3
1Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
Insights
Elevated levels of kidney injury molecule-1 (KIM-1), soluble urokinase plasminogen activator receptor (suPAR), tumor necrosis factor receptor 1 (TNFR-1), and TNFR-2 predict chronic kidney disease (CKD) development in the general population. These biomarkers may aid in identifying individuals at risk for kidney disease.
Area of Science:
- Nephrology
- Biomarker Research
- Epidemiology
Background:
- Biomarkers for chronic kidney disease (CKD) progression are known in diabetic patients.
- Their association with incident CKD in the general population is less understood.
Purpose of the Study:
- To investigate the association between plasma biomarkers and incident CKD in individuals without diabetes or pre-existing CKD.
- To assess the predictive value of these biomarkers for CKD development.
Main Methods:
- Prospective observational cohort study of 948 participants from the Atherosclerosis Risk in Communities study.
- Baseline plasma levels of KIM-1, MCP-1, suPAR, TNFR-1, TNFR-2, and YKL-40 were measured.
- Incident CKD was defined by eGFR decline or dialysis dependence over 15 years, analyzed using logistic regression.
Main Results:
- Higher concentrations of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with increased odds of incident CKD.
- After adjustment, KIM-1 and suPAR remained significant predictors.
- Adding these biomarkers improved the predictive model's C statistic and risk stratification.
Conclusions:
- Elevated KIM-1, suPAR, TNFR-1, and TNFR-2 levels are associated with a higher risk of developing CKD in individuals without diabetes.
- These biomarkers show potential for early identification of individuals at risk for kidney disease.
Rationale & Objective:
Biomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established.
Study Design:
Prospective observational cohort.
Setting & Participants:
In the Atherosclerosis Risk in Communities) study, 948 participants were studied.
Exposures:
The baseline plasma biomarkers of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), soluble urokinase plasminogen activator receptor (suPAR), tumor necrosis factor receptor 1 (TNFR-1), tumor necrosis factor receptor 2 (TNFR-2), and human cartilage glycoprotein-39 (YKL-40) measured in 1996-1998.
Outcome:
Incident CKD after 15 years of follow-up defined as ≥40% estimated glomerular filtration rate decline to <60 mL/min/1.73 m2 or dialysis dependence through United States Renal Data System linkage.
Analytical Approach:
Logistic regression and C statistics.
Results:
There were 523 cases of incident CKD. Compared with a random sample of 425 controls, there were greater odds of incident CKD per 2-fold higher concentration of KIM-1 (OR, 1.49; 95% CI, 1.25-1.78), suPAR (OR, 2.57; 95% CI, 1.74-3.84), TNFR-1 (OR, 2.20; 95% CI, 1.58-3.09), TNFR-2 (OR, 2.03; 95% CI, 1.37-3.04). After adjustment for all biomarkers, KIM-1 (OR, 1.42; 95% CI, 1.19-1.71), and suPAR (OR, 1.86; 95% CI, 1.18-2.92) remained associated with incident CKD. Compared with traditional risk factors, the addition of all 6 biomarkers improved the C statistic from 0.695-0.731 (P < 0.01) and using the observed risk of 12% for incident CKD, the predicted risk gradient changed from 5%-40% (for the 1st-5th quintile) to 4%-44%.
Limitations:
Biomarkers and creatinine were measured at one time point.
Conclusions:
Higher levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with higher odds of incident CKD among individuals without diabetes.
Plain-Language Summary:
For people with diabetes or kidney disease, several biomarkers have been shown to be associated with worsening kidney disease. Whether these biomarkers have prognostic significance in people without diabetes or kidney disease is less studied. Using the Atherosclerosis Risk in Communities study, we followed individuals without diabetes or kidney disease for an average of 15 years after biomarker measurement to see if these biomarkers were associated with the development of kidney disease. We found that elevated levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with the development of kidney disease. These biomarkers may help identify individuals who would benefit from interventions to prevent the development of kidney disease.
Related Concept Videos
01:25Chronic Kidney Disease I: Introduction
01:24Chronic Kidney Disease II: Clinical Manifestations
01:28Chronic Kidney Disease III: Interprofessional Care
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
01:29Acute Kidney Injury III: Clinical Manifestations