Renal Effects of SGLT2 Inhibitors: An Update

Authors and Disclosures

Josselin Nespoux^a and Volker Vallon<sup>b,c

a</sup>British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK, ^bDepartment of Medicine, University of California, San Diego & VA San Diego Healthcare System and ^cDepartment of Pharmacology, University of California San Diego, San Diego, USA

Correspondence to
Volker Vallon, MD, Division of Nephrology & Hypertension, Department of Medicine, University of California San Diego & VA San Diego Healthcare System, 3350 La Jolla Village Drive (9151), San Diego, CA 92161, USA. Tel: +1 858 552 8585 x5945; e-mail: vvallon@ucsd.edu

Conflicts of interest
Over the past 36 months, V.V. has served as a consultant and received honoraria from Astra-Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceutical and Merck, and received grant support for investigator-initiated research from Astra-Zeneca, Bayer, Boehringer Ingelheim, Fresenius, and Janssen Pharmaceutical. J.N. has no conflicts of interest.

Sidebar

Key Points

• SGLT2 inhibition improves renal and cardiovascular outcomes in patients with CKD despite lesser blood glucose-lowering indicating a role for effects independent of glycemia control, and as a consequence, studies to define the effects of SGLT2 inhibitors on renal and cardiovascular outcomes in nondiabetic patients are on the way.

• By lowering hyperfiltration at the onset of therapy, SGLT2 inhibition reduces tubular metabolic demand and helps preserving GFR in the long-term, which possibly involves improving cortical oxygenation and preserving tubular mitochondrial function and autophagy.

• Mathematical modeling provided new insights that may explain why renal and cardiovascular effects in response to SGLT2 inhibition are preserved in CKD despite reduced blood glucose effects.

• SGLT2 inhibition also decreases the risk and severity of AKI, a known contributor to CKD development.

• SGLT1 in the macula densa senses luminal glucose and via stimulation of NOS1 contributes to diabetic glomerular hyperfiltration, a pathway that is expected to modulate the GFR response to SGLT2 inhibition.