Background: Despite optimal management of diabetic kidney disease (DKD)
with intensive glycemic control and administration of agents blocking the renin-angiotensinaldosterone-
system, the residual risk for nephropathy progression to end-stage-renal-disease
(ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent
a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their
glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial
evidence supporting a protective effect of SGLT-2 inhibitors on DKD.
Methods: A systematic literature search of bibliographic databases was conducted to identify
preclinical studies and randomized trials evaluating the effects SGLT-2 inhibitors on
Results: Preclinical studies performed in animal models of DKD support the renoprotective
action of SGLT-2 inhibitors showing that these agents exert albuminuria-lowering effects
and reverse glomerulosclerosis. The renoprotective action of SGLT-2 inhibitors is strongly
supported by human studies showing that these agents prevent the progression of albuminuria
and retard nephropathy progression to ESRD. This beneficial effect of SGLT-2 inhibitors
is not fully explained by their glucose-lowering properties. Attenuation of glomerular hyperfiltration
and improvement in a number of surrogate risk factors, including associated reduction
in systemic blood pressure, body weight, and serum uric acid levels may represent plausible
mechanistic explanations for the cardio-renal protection offered by SGLT-2 inhibitors.
Furthermore, the tubular cell metabolism seems to be altered towards a ketone-prone pathway
with protective activities.
Conclusion: SGLT-2 inhibition emerges as a novel therapeutic approach to type 2 diabetes
with anticipated benefits towards cardio-renal risk reduction. Additional research efforts are
clearly warranted to elucidate this favorable effect in patients with overt DKD.
Keywords: albuminuria, diabetic nephropathy, ESRD, SGLT-2.
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