Glycolytic lactate in diabetic kidney disease.

Autor: Darshi M; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Kugathasan L; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Canada., Maity S; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Sridhar VS; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Canada., Fernandez R; Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, Texas, USA., Limonte CP; Schools of Medicine and Public Health, University of Washington, Seattle, Washington, USA., Grajeda BI; Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, El Paso, Texas, USA., Saliba A; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Zhang G; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Drel VR; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Kim JJ; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Montellano R; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Tumova J; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Montemayor D; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., Wang Z; Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, Texas, USA., Liu JJ; Clinical Research Unit, Khoo Teck Puat Hospital, Singapore., Wang J; Clinical Research Unit, Khoo Teck Puat Hospital, Singapore., Perkins BA; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Canada., Lytvyn Y; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Canada., Natarajan L; Herbert Wertheim School of Public Health, University of California, San Diego, La Jolla, California USA., Lim SC; Clinical Research Unit & Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore.; Saw Swee Hock School of Public Heath, National University of Singapore, Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore., Feldman H; Center for Clinical Epidemiology and Biostatistics and.; Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Toto R; Department of Internal Medicine, University of Texas Southwestern Medical Center, Texas, USA., Sedor JR; Glickman Urology and Kidney and Lerner Research Institutes, Cleveland Clinic, Cleveland, Ohio, USA., Patel J; Department of Internal Medicine, University of Texas Southwestern Medical Center, Texas, USA., Waikar SS; Section of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA., Brown J; Division of Nephrology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA., Osman Y; Division of Nephrology, Department of Medicine, Wayne State University, Detroit, Michigan, USA., He J; School of Public Health, Tulane University Medical Center, New Orleans, Louisiana, USA., Chen J; Division of Nephrology, Department of Medicine, New Orleans, Louisiana, USA., Reeves WB; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA., de Boer IH; Schools of Medicine and Public Health, University of Washington, Seattle, Washington, USA., Roy S; Department of Biological Sciences and Border Biomedical Research Center, University of Texas at El Paso, El Paso, Texas, USA., Vallon V; Department of Medicine, University of California, San Diego, La Jolla, California, USA.; VA San Diego Healthcare Center, San Diego, California, USA., Hallan S; Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Nephrology, St. Olav Hospital, Trondheim, Norway., Gelfond JA; Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, Texas, USA., Cherney DZ; Division of Nephrology, Department of Medicine, University Health Network, Toronto, Canada., Sharma K; Center for Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2024 Jun 10; Vol. 9 (11). Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1172/jci.insight.168825
Abstrakt: 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.
Databáze: MEDLINE