Circulating Tumor Necrosis Factor Receptors: A Potential Biomarker for the Progression of Diabetic Kidney Disease
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Published on: May 2, 2025
Maki Murakoshi1, Tomohito Gohda1, Yusuke Suzuki1
1Department of Nephrology, Juntendo University Faculty of Medicine. 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Insights
Tumor necrosis factor receptors (TNFRs) play a role in diabetic kidney disease (DKD) progression. Higher TNFR levels are linked to worse kidney function, increased albuminuria, and higher mortality risk in diabetic patients.
Area of Science:
- Nephrology
- Endocrinology
- Immunology
Background:
- Diabetic kidney disease (DKD) poses a significant therapeutic challenge, with cardiovascular events often preceding end-stage renal disease (ESRD).
- Inflammation, particularly involving tumor necrosis factor (TNF) biomarkers, is implicated in DKD development and progression.
- Patients with DKD and ESRD exhibit a poor prognosis, highlighting the need for better understanding and treatment strategies.
Purpose of the Study:
- To review the molecular roles of TNF receptors (TNFRs) in DKD.
- To examine the association between serum TNFR concentrations and key DKD indicators: albuminuria, estimated glomerular filtration rate (eGFR) decline, and all-cause mortality.
- To explore the potential of TNFRs as therapeutic targets or prognostic markers in DKD.
Main Methods:
- Review of experimental studies investigating the TNFα-TNFR2 inflammatory pathway in DKD.
- Analysis of observational studies correlating serum TNFR levels with albuminuria and eGFR.
- Statistical analysis of the independent effect of circulating TNFRs on mortality and renal function decline, adjusted for known risk factors.
Main Results:
- Experimental evidence suggests DKD progression involves the TNFα-TNFR2 inflammatory pathway.
- Serum TNFR levels positively correlate with albuminuria and negatively with eGFR.
- Circulating TNFR levels independently predict all-cause mortality, eGFR decline, and ESRD risk in diabetic patients.
Conclusions:
- TNF receptors are significantly associated with DKD progression and adverse outcomes.
- Serum TNFR levels serve as potential biomarkers for predicting mortality and renal function decline in DKD.
- Further research is warranted to fully elucidate the precise function of TNFRs and their therapeutic potential in managing DKD.
Abstract:
Despite considerable advancements in medicine, the optimal treatment for chronic kidney disease (CKD), especially diabetic kidney disease (DKD), remains a major challenge. More patients with DKD succumb to death due to cardiovascular events than due to progression to end-stage renal disease (ESRD). Moreover, patients with DKD and ESRD have remarkably poor prognosis. Current studies have appreciated the contribution of inflammation and inflammatory mediators, such as tumor necrosis factor (TNF)-related biomarkers, on the development/progression of DKD. The present review focuses on molecular roles, serum concentrations of TNF receptors (TNFRs), and their association with increased albuminuria, eGFR decline, and all-cause mortality in diabetes. Experimental studies have suggested that DKD progression occurs through the TNFα-TNFR2 inflammatory pathway. Moreover, serum TNFR levels were positively associated with albuminuria and negatively associated with estimated glomerular filtration rate (eGFR), while circulating levels of TNFRs exhibited an independent effect on all-cause mortality and eGFR decline, including ESRD, even after adjusting for existing risk factors. However, their precise function has yet to be elucidated and requires further studies.
