ArticleJCI insight2024
Glycolytic lactate in diabetic kidney disease.
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Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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44citing papers in PubMed, 1 pooled it
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Integrated bioinformatics analysis uncovers TNFSF10 as a key panoptosis-related gene in diabetic tubular injury.Renal failure · 2026Article
- Lactate induces renal lipid accumulation and aggravates renal fibrosis by inhibiting the PPARα signaling pathway and fatty acid oxidation.Renal failure · 2026Article
- Sodium Butyrate Attenuates Renal Fibrosis by Regulating Glycolysis and Histone H4K12 Lactylation in Diabetic Kidney Disease.Diabetes, obesity & metabolism · 2026Article
- Metabolic control by liver-kidney crosstalk and glucagon in health and disease.Nature reviews. Nephrology · 2026Review
- Tubular PFKFB3 drives diabetic kidney fibrosis via lactate‑dependent H4K12 lactylation and HIPK2 transactivation.International journal of molecular medicine · 2026Article
- Mrpl50 integrates glucolipotoxicity with hypoxia-inducible factor 1 alpha signaling to drive diabetic kidney disease.The Journal of biological chemistry · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Hyperlactatemia in sepsis and shock: a renal metabolic perspective.Critical care (London, England) · 2026Review
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- AARS1 promotes diabetic kidney disease through rewiring Akt and NF-κB signaling to suppress autophagy and sustain inflammation.Cellular & molecular biology letters · 2026Article
- Unraveling the therapeutic potential of luteolin in renal pathology: a comprehensive pathway oriented approach.Pharmacological reports : PR · 2026Review
- Retrospective Cohort Analysis of TyG, TyG-SI, and TyG-Lac Indices as Predictors of 360-Day Mortality in Critically Ill Ischemic Stroke Patients.Journal of clinical medicine · 2026Article
- Lactylation: a metabolic-epigenetic bridge in diabetic kidney disease and a therapeutic target for TCM.Chinese medicine · 2026Review
- Lactylation-mitochondria axis in chronic kidney disease: metabolic reprogramming, epigenetic dysregulation, and therapeutic potential.Molecular and cellular biochemistry · 2026Review
- Improving erectile function in diabetic male mice by rescuing depalmitoylated FBP1 to reduce cavernosal lactate.Nature communications · 2026Article
- Sex-specific differences in vascular circulation and metabolic regulation associated with aging and cardiovascular health problems.Frontiers in aging · 2026Article
- Multiomics Mendelian Randomization Identifies Lactylation-Related Molecular Traits in Type 1 Diabetes.Journal of diabetes research · 2026Article
- Advances in the Identification of Novel Urinary Biomarkers for Diabetic Kidney Disease.Journal of diabetes research · 2026Review
Corrections and comments
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Authors and funding
39 authors.
Manjula DarshiCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Luxcia KugathasanDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Canada.
Soumya MaityCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Vikas S SridharDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Canada.
Roman FernandezDepartment of Population Health Sciences, University of Texas Health San Antonio, San Antonio, Texas, USA.
Christine P LimonteSchools of Medicine and Public Health, University of Washington, Seattle, Washington, USA.
Brian I GrajedaDepartment of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, El Paso, Texas, USA.
Afaf SalibaCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Guanshi ZhangCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Viktor R DrelCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Jiwan J KimCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Richard MontellanoCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Jana TumovaCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Daniel MontemayorCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Zhu WangDepartment of Population Health Sciences, University of Texas Health San Antonio, San Antonio, Texas, USA.
Jian-Jun LiuClinical Research Unit, Khoo Teck Puat Hospital, Singapore.
Jiexun WangClinical Research Unit, Khoo Teck Puat Hospital, Singapore.
Bruce A PerkinsDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Canada.
Yuliya LytvynDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Canada.
Loki NatarajanHerbert Wertheim School of Public Health, University of California, San Diego, La Jolla, California USA.
Su Chi LimClinical Research Unit & Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore.
Harold FeldmanCenter for Clinical Epidemiology and Biostatistics and.
Robert TotoDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Texas, USA.
John R SedorGlickman Urology and Kidney and Lerner Research Institutes, Cleveland Clinic, Cleveland, Ohio, USA.
Jiten PatelDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Texas, USA.
Sushrut S WaikarSection of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA.
Julia BrownDivision of Nephrology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
Yahya OsmanDivision of Nephrology, Department of Medicine, Wayne State University, Detroit, Michigan, USA.
Jiang HeSchool of Public Health, Tulane University Medical Center, New Orleans, Louisiana, USA.
Jing ChenDivision of Nephrology, Department of Medicine, New Orleans, Louisiana, USA.
W Brian ReevesCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Ian H de BoerSchools of Medicine and Public Health, University of Washington, Seattle, Washington, USA.
Sourav RoyDepartment of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, El Paso, Texas, USA.
Volker VallonDepartment of Medicine, University of California, San Diego, La Jolla, California, USA.
Stein HallanDepartment of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Jonathan Al GelfondDepartment of Population Health Sciences, University of Texas Health San Antonio, San Antonio, Texas, USA.
David Zi CherneyDivision of Nephrology, Department of Medicine, University Health Network, Toronto, Canada.
Kumar SharmaCenter for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Kidney Precision Medicine Project, and the CRIC Study Investigators
Funding
Continuation of the Coordinating Center for the Chronic Renal Insufficiency Cohort (CRIC) StudyU24DK060990 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Amanda Hyre Anderson, Laura M Dember · 2018 to 2026
$21.5MCentral Hub for Kidney Precision MedicineU24DK114886 · NIDDK · UNIVERSITY OF WASHINGTON · PI Jonathan Himmelfarb, Matthias Kretzler · 2022 to 2026
$21.1MConProject-002U2CDK114886 · NIDDK · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN, IYENGAR, SRINIVAS RAVI V · 2017 to 2021
$21.0MUAB-UCSD O'Brien Core Center for Acute Kidney Injury ResearchP30DK079337 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SANDERS, PAUL W. · 2008 to 2022
$18.3MKPMP Kidney Mapping and Atlas Project (KMAP)U01DK133090 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jonathan Himmelfarb, Matthias Kretzler · 2022 to 2026
$10.4MNovel Paradigms in Diabetic ComplicationsDP3DK094352 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHARMA, KUMAR · 2011 to 2011
$6.0MUAB-UCSD O'Brien Center for Acute Kidney Injury ResearchU54DK137307 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Javier A. Neyra · 2023 to 2026
$4.4MGlomerular and Tubular Function in the Diabetic KidneyR01DK112042 · NIDDK · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI SCOTT Culver THOMSON, Volker Vallon · 2017 to 2026
$4.1MSpatial Multi-Omics to Profile Metabolic Pathways for Kidney DiseaseU01DK114920 · NIDDK · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Christopher R Anderton, Kumar Sharma · 2022 to 2026
$3.9MBoston Chronic Kidney Disease Research Biopsy CenterU01DK133092 · NIDDK · BOSTON MEDICAL CENTER · PI Sylvia E Rosas, Sushrut S. Waikar · 2022 to 2026
$3.5MThe Contribution of Kidney Disease to Age-Associated Cognitive DeclineRF1AG061296 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI MAHER, PAMELA ANNE · 2019 to 2019
$3.2MPREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE)U01DK114907 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Nir Hacohen, Jeffrey Benton Hodgin · 2022 to 2026
$3.2MBLRD VA I01 BX001340NHLBI NIH HHS R01 HL142814NIA NIH HHS RF1 AG061296NIDDK NIH HHS DP3 DK094352NIDDK NIH HHS P30 DK079337NIDDK NIH HHS R01 DK106102NIDDK NIH HHS R01 DK110541NIDDK NIH HHS R01 DK112042NIDDK NIH HHS R43 DK130732NIDDK NIH HHS U01 DK114907NIDDK NIH HHS U01 DK114908NIDDK NIH HHS U01 DK114920NIDDK NIH HHS U01 DK133081NIDDK NIH HHS U01 DK133090NIDDK NIH HHS U01 DK133092NIDDK NIH HHS U01 DK133095NIDDK NIH HHS U24 DK060990NIDDK NIH HHS U24 DK114886NIDDK NIH HHS U2C DK114886NIDDK NIH HHS U54 DK137307NIDDK NIH HHS UH3 DK114861NIDDK NIH HHS UH3 DK114866NIDDK NIH HHS UH3 DK114870NIDDK NIH HHS UH3 DK114907NIDDK NIH HHS UH3 DK114908NIDDK NIH HHS UH3 DK114915NIDDK NIH HHS UH3 DK114920NIDDK NIH HHS UH3 DK114923NIDDK NIH HHS UH3 DK114926NIDDK NIH HHS UH3 DK114933NIDDK NIH HHS UH3 DK114937
Abstract
Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.
Indexed as
Diabetes Mellitus, Type 1Diabetes Mellitus, Type 2Diabetic NephropathiesGlycolysisLactic AcidAdultAgedAnimalsBiomarkersFemaleGlomerular Filtration RateGlucoseHumansKidney Tubules, ProximalMaleMiceBiomarkersGlucoseLactic AcidSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsChronic kidney diseaseDiabetesMitochondriaNephrology
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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 Socratic graph.