Evidence map›Paper›PMID 42997246›Full record

ReviewFrontiers in endocrinology2026

Metabolites as key signaling mediators: rethinking diabetic kidney disease from a network perspective.

Xin Li, Xu Wang, Cheng Fang, Zhonghong Yan, Lei Liu, Jinwei Han, Liangyou Zhao, Xiuhong Wu

Abstract readReview
In one paragraph

Review in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Xin Li *State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, China.
Xu Wang *State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, China.
Cheng FangHeilongjiang University of Chinese Medicine, Harbin, China.
Zhonghong YanHeilongjiang University of Chinese Medicine, Harbin, China.
Lei LiuHeilongjiang University of Chinese Medicine, Harbin, China.
Jinwei HanQiqihar Medical University, Qiqihar, China.
Liangyou ZhaoHeilongjiang University of Chinese Medicine, Harbin, China.
Xiuhong WuState Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease worldwide. Current diagnostic approaches rely mainly on albuminuria and eGFR, but these are insufficiently sensitive for detecting early lesions, and treatment options remain limited. Metabolites are not merely byproducts of metabolism but serve as central signaling hubs that orchestrate DKD progression. These metabolites can act as receptor ligands, substrates for epigenetic modifications, and cargoes of extracellular vesicles. Together, they form a complex metabolic signaling network that links systemic metabolic disturbances to local kidney injury. Adopting this metabolite-centric new perspective transforms DKD from a collection of isolated pathways into a systemic, network-level disease. Recent advances in multidimensional metabolomics technologies-including static profiling, spatial metabolomics, metabolic flux analysis, and multi-omics approaches-enable us to dissect the metabolic network of DKD with unprecedented resolution. This review synthesizes current knowledge on metabolite-driven mechanisms, including the AGEs-RAGE pathway, lipotoxicity, amino acid reprogramming, and EV-mediated crosstalk. It systematically categorizes metabolite biomarkers according to their clinical functions, covering early detection, progression prediction, and pathogenic drivers. In addition, emerging therapeutic strategies targeting specific metabolic nodes are discussed. Finally, building on these established findings, we propose a hypothetical roadmap toward metabolic precision medicine. This framework hypothesizes the stratification of patients into distinct metabolic phenotypes, such as the high-TMAO, high-BCAAs, and high-AGEs subtypes. It suggests that treatment regimens could be selected based on the underlying metabolic mechanisms and that therapeutic responses could be assessed by dynamic monitoring of circulating metabolites. If validated, this conceptual strategy holds promise for overcoming current diagnostic and therapeutic bottlenecks and improving outcomes for patients with DKD.

Indexed as

Diabetic NephropathiesMetabolic Networks and PathwaysSignal TransductionAnimalsBiomarkersHumansMetabolomicsBiomarkersbiomarkersdiabetic kidney diseasekidneymetabolitesspatial metabolomics

Identifiers

PMID42997246
PMCPMC13741093

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.