Abstract
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.
Keywords:
KIM-1; MCP-1; SGLT-2; acute kidney injury; dapagliflozin; type 2 diabetes.
© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
Publication types
-
Clinical Trial
-
Randomized Controlled Trial
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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
-
Benzhydryl Compounds / adverse effects
-
Benzhydryl Compounds / therapeutic use*
-
Biomarkers / blood
-
Biomarkers / urine
-
Cross-Over Studies
-
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
-
Glomerular Filtration Rate / drug effects
-
Glucosides / adverse effects
-
Glucosides / therapeutic use*
-
Hepatitis A Virus Cellular Receptor 1 / metabolism
-
Humans
-
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
-
Netherlands
-
Renal Elimination / drug effects
-
Sodium-Glucose Transporter 2 Inhibitors / adverse effects
-
Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
Benzhydryl Compounds
-
Biomarkers
-
Glucosides
-
HAVCR1 protein, human
-
Hepatitis A Virus Cellular Receptor 1
-
IL6 protein, human
-
Inflammation Mediators
-
Interleukin-6
-
Sodium-Glucose Transporter 2 Inhibitors
-
dapagliflozin