Effects of the SGLT‐2 inhibitor dapagliflozin on glomerular and tubular injury markers

• Published in: Diabetes, obesity & metabolism Vol. 20; no. 8; pp. 1988 - 1993
• Main Authors: Dekkers, Claire C. J., Petrykiv, Sergei, Laverman, Gozewijn D., Cherney, David Z., Gansevoort, Ron T., Heerspink, Hiddo J. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2018; Wiley Subscription Services, Inc
• Subjects: acute kidney injury; Acute Kidney Injury - complications; Acute Kidney Injury - immunology; Acute Kidney Injury - prevention & control; Adult; Albuminuria - etiology; Albuminuria - prevention & control; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antidiabetics; Benzhydryl Compounds - adverse effects; Benzhydryl Compounds - therapeutic use; Biomarkers - blood; Biomarkers - urine; Brief Report; Brief Reports; Cell injury; Cross-Over Studies; dapagliflozin; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetic Nephropathies - immunology; Diabetic Nephropathies - prevention & control; Double-Blind Method; Epidermal growth factor receptors; Excretion; Glomerular Filtration Rate - drug effects; Glucosides - adverse effects; Glucosides - therapeutic use; Hepatitis A Virus Cellular Receptor 1 - metabolism; Humans; Immunoglobulin G; Inflammation; Inflammation Mediators - blood; Inflammation Mediators - urine; Interleukin-6 - urine; Kidney Glomerulus - drug effects; Kidney Glomerulus - immunology; Kidney Glomerulus - physiopathology; Kidney Tubules - drug effects; Kidney Tubules - immunology; Kidney Tubules - physiopathology; KIM‐1; MCP‐1; Netherlands; Renal Elimination - drug effects; SGLT‐2; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; type 2 diabetes; Netherlands; KIM-1; MCP-1; acute kidney injury; type 2 diabetes; dapagliflozin; SGLT-2
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.13301

The mechanisms by which SGLT‐2 inhibitors lower albuminuria are incompletely understood. We assessed in a post‐hoc analysis of a cross‐over trial the effects of the SGLT2 inhibitor dapagliflozin on glomerular markers (IgG to IgG4 and IgG to albumin), tubular markers (urinary KIM‐1, NGAL and LFABP) and inflammatory markers (urinary MCP‐1 and IL‐6) to provide more insight into kidney protective effects. Dapagliflozin decreased albuminuria by 43.9% (95% CI, 30.3%‐54.8%) and eGFR by 5.1 (2.0‐8.1) mL/min/1.73m2 compared to placebo. Dapagliflozin did not change glomerular charge or size selectivity index compared to placebo. Dapagliflozin decreased urinary KIM‐1 excretion by 22.6% (0.3%‐39.8%; P = .05) and IL‐6 excretion by 23.5% (1.4%‐40.6%; P = .04) compared to placebo, whereas no changes in NGAL, LFABP and MCP‐1 were observed. During dapagliflozin treatment, changes in albuminuria correlated with changes in eGFR (r = 0.36; P = .05) and KIM‐1 (r = 0.39; P = .05). In conclusion, the albuminuria‐lowering effect of 6 weeks of dapagliflozin therapy may be the result of decreased intraglomerular pressure or reduced tubular cell injury.