Journal Article

Renal Effects of Sodium-Glucose Co-Transporter Inhibitors

Thomson, Scott C., Vallon, Volker

2019

Overview

Sodium-glucose co-transporter 2 (SGLT2) inhibitors immediately reduce the glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus. When given chronically, they confer benefit by markedly slowing the rate at which chronic kidney disease progresses and are the first agents to do so since the advent of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Salutary effects on the kidney were first demonstrated in cardiovascular outcomes trials and have now emerged from trials enriched in subjects with type 2 diabetes mellitus and chronic kidney disease. A simple model that unifies the immediate and long-term effects of SGLT2 inhibitors on kidney function is based on the assumption that diabetic hyperfiltration puts the kidney at long-term risk and evidence that hyperfiltration is an immediate response to a reduced signal for tubuloglomerular feedback, which occurs to the extent that SGLT2 activity mediates a primary increase in sodium and fluid reabsorption by the proximal tubule. This model will likely continue to serve as a useful description accounting for the beneficial effect of SGLT2 inhibitors on the diabetic kidney, similar to the hemodynamic explanation for the benefit of ACEIs and ARBs. A more complex model will be required to incorporate positive interactions between SGLT2 and sodium-hydrogen exchanger 3 in the proximal tubule and between sodium-glucose co-transporter 1 (SGLT1) and nitric oxide synthase in the macula densa. The implication of these latter nuances for day-to-day clinical medicine remains to be determined.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Angiotensin / Angiotensin-converting enzyme inhibitors / Cardiovascular disease / Clinical medicine / Clinical trials / Diabetes / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - metabolism / Diabetic kidney disease / Disease Progression / Drugs / Energy / Glomerular filtration / Glomerular filtration rate / Glomerular Filtration Rate - drug effects / Glomerular Filtration Rate - physiology / Glucose / Glucose transporter / Hemodynamics / Humans / Kidney - drug effects / Kidney diseases / Kidney Tubules - drug effects / Kidney Tubules - metabolism / Kidney Tubules, Distal - drug effects / Kidney Tubules, Distal - metabolism / Kidney Tubules, Proximal - drug effects / Kidney Tubules, Proximal - metabolism / Long-term effects / Metabolism / Na+/H+-exchanging ATPase / Nitric oxide / Nitric Oxide Synthase - metabolism / Nitric-oxide synthase / Peptidyl-dipeptidase A / Proximal tubule / Reabsorption / Renal Circulation - drug effects / Renal Circulation - physiology / Renal Insufficiency, Chronic - complications / Renal Insufficiency, Chronic - metabolism / Sodium / Sodium-Glucose Transporter 1 - metabolism / Sodium-Glucose Transporter 2 - metabolism / Sodium-Glucose Transporter 2 Inhibitors - pharmacology / Sodium-Glucose Transporter 2 Inhibitors - therapeutic use / Sodium-Hydrogen Exchanger 3 - metabolism / Theory / Tubuloglomerular feedback / Urine