Trial reportDiabetes, obesity & metabolism2022
Mechanisms of action of the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin on tubular inflammation and damage: A post hoc mediation analysis of the CANVAS trial.
Trial report in Diabetes, obesity & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Management of subjects with type 2 diabetes hospitalized in internal medicine units: a cluster-randomized, multicenter study before and after an educational program.Internal and emergency medicine · 2026Trial
- Effect of empagliflozin on urinary albumin excretion and hypoxic biomarkers in early diabetic kidney disease: A randomised double-blind, placebo-controlled trial.Diabetes, obesity & metabolism · 2026Trial
- Effect of administration and withdrawal of the sodium-glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single-arm study (RESTORE-nephropathy study).Journal of diabetes investigation · 2025Trial
- Effects of dapagliflozin and dapagliflozin-saxagliptin on erythropoiesis, iron and inflammation markers in patients with type 2 diabetes and chronic kidney disease: data from the DELIGHT trial.Cardiovascular diabetology · 2023 · on this mapTrial
- Mechanisms of action of the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin on tubular inflammation and damage: A post hoc mediation analysis of the CANVAS trial.Diabetes, obesity & metabolism · 2022 · on this mapTrial
- Urinary Biomarkers for the Risk Assessment and Management of Heart Failure: Pearls and Pitfalls.Current heart failure reports · 2026Review
- More than Glucose Elimination: Additional Benefits of SGLT2 Inhibitors in Glomerular Diseases.Drugs · 2026Review
- SGLT2 Inhibitors, Muscle Loss, and Creatinine-Based Estimated GFR: An Integrative Conceptual Review of Renoprotection.Kidney medicine · 2026Review
- Urine as a source of biomarkers and biological knowledge in chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Empagliflozin and Ultrafiltration Volume in Patients Undergoing Peritoneal Dialysis.Kidney international reports · 2026Article
- Review
- Mitochondrial Quality Control Systems in Septic AKI: Molecular Mechanisms and Therapeutic Implications.International journal of medical sciences · 2025Article
- Evaluating the Safety and Efficacy of SGLT-2 Inhibitors on Reducing Cardiovascular and Renal Mortality, Morbidity and Inflammatory Outcomes in Various Patient Populations: A Systematic Review and Meta-Analysis of 92 920 Patients.Clinical Medicine Insights. Cardiology · 2025Article
- Insights into the Novel Biomarkers Expressed in Diabetic Nephropathy: Potential Clinical Applications.Current pharmaceutical design · 2025Review
- The association between sodium-glucose cotransporter 2 inhibitors and contrast-associated acute kidney injury in patients with type 2 diabetes undergoing angiography: a propensity-matched study.European journal of medical research · 2024Article
- Longitudinal Trajectories of Biomarkers of Kidney Tubular Function in Type 1 Diabetes.Kidney international reports · 2024Article
- Effect of SGLT2 inhibitors on the proteinuria reduction in patients with IgA nephropathy.Frontiers in medicine · 2023Article
- SGLT2 inhibitors suppress epithelial-mesenchymal transition in podocytes under diabetic conditionsFrontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo test the hypothesis that the reduction in urinary kidney injury molecule-1 (KIM-1) observed with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin is mediated through its effects on urine albumin to creatinine ratio (UACR) and monocyte chemoattractant protein-1 (MCP-1) by assessing the proportion of the effect of canagliflozin on KIM-1 that is mediated through its effects on MCP-1 and UACR in patients with type 2 diabetes and albuminuric kidney disease. MATERIAL AND
methodsWe measured KIM-1 and MCP-1 levels in urine samples from the CANVAS trial at baseline and Week 52 with the Mesoscale QuickPlex SQ 120 platform. KIM-1 and MCP-1 were standardized by urinary creatinine (Cr). The proportion of the effect of canagliflozin that is mediated through UACR and MCP-1/Cr on KIM-1/Cr was estimated with G-computation.
resultsIn total, 763 patients with micro- or macroalbuminuria (17.6% of the total cohort) were included. Baseline characteristics were well balanced between the canagliflozin and placebo group. At Year 1, canagliflozin compared to placebo reduced UACR, MCP-1/Cr and KIM-1/Cr by 40.4% (95% CI 31.0, 48.4), 18.1% (95% CI 8.9, 26.4) and 30.9% (95% CI 23.0, 38.0), respectively. The proportion of the effect of canagliflozin on KIM-1/Cr mediated by its effect on UACR and in turn on MCP-1/Cr was 15.2% (95% CI 9.4, 24.5).
conclusionCanagliflozin reduces urinary KIM-1, suggesting decreased tubular damage. This effect was partly mediated through a reduction in MCP-1, indicative of reduced tubular inflammation, which was in turn mediated by a reduction in UACR. This post hoc analysis suggests that urinary albumin leakage may lead to tubular inflammation and induction of injury, and provide mechanistic insight for how canagliflozin may ameliorate tubular damage, but further research is required to confirm these findings.
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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.