12-OR: Urine Lactate Is a Disease Biomarker for Diabetic Kidney Disease
Bibliographic record
Abstract
As lactate (LA) elevation is associated with mitochondrial dysfunction, we examined the role of LA in diabetic kidney disease (DKD) progression. Urine LA (ULA) was measured in patients with type 2 diabetes (T2D) in three independent cohort studies (HUNT3, SMART2D, and CRIC). ULA and plasma LA (PLA) were also measured in patients with type 1 diabetes (T1D) following eu- or hyperglycemic clamp, in mouse kidney sections, and sodium-glucose cotransporter-2 (SGLT2)-deficient mice. Mitochondrial functional changes in human kidney proximal tubule (HK2) cells were assayed in response to exogenous LA. Subjects in HUNT3 with DKD (n=39) had elevated ULA levels compared to healthy controls (n=53, p=0.023) (Fig. 1). In subjects with T2D from SMART2D (n=230) and CRIC (n=889), the third tertile of ULA/creatinine ratio was associated with a greater estimated glomerular filtration rate (eGFR) decline [-1.63 mL/min/1.73m2/year, p=0.007, and -0.63 mL/min/1.73m2, p=0.042], relative to the first tertile. Acute hyperglycemia stimulated PLA (p<0.0001) and ULA (p=0.001) in patients with T1D (n=39), and in kidney sections incubated with high glucose. Compared to wild-type, SGLT2-deficient mice had lower ULA levels. LA above 2.5 mM inhibited oxygen consumption rate in HK2 cells. Elevated ULA/creatinine ratio inhibits mitochondrial function in diabetes and identifies subjects at risk of rapid renal decline independent of chronic glycemic control. Disclosure L.Kugathasan: None. L.Natarajan: None. S.Lim: None. S.Waikar: None. Y.M.Osman: None. J.He: None. V.Vallon: Research Support; NIH - National Institutes of Health, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Maze Therapeutics, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca. S.Hallan: None. D.Cherney: Other Relationship; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. K.Sharma: Advisory Panel; Reata Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc. Cric study investigators: n/a. M.Darshi: Employee; Janssen Research & Development, LLC. V.Srinivasan sridhar: Other Relationship; Merck & Co., Inc. V.Drel: None. J.Tumova: None. J.Liu: None. J.Wang: None. B.A.Perkins: Advisory Panel; Dexcom, Inc., Insulet Corporation, Novo Nordisk, Sanofi, Vertex Pharmaceuticals Incorporated, Other Relationship; Abbott, Medtronic, Sanofi, Research Support; Novo Nordisk, Bank of Montreal (BMO). Y.Lytvyn: None.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".