When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I<sup>2</sup>=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I<sup>2</sup>=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I<sup>2</sup>=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I<sup>2</sup>=1.3%).
SGLT2 inhibitors reduced the risk of dialysis, transplantation, or death due to kidney disease in individuals with type 2 diabetes and provided protection against acute kidney injury.
Given the raising clinical use of SGLT2 inhibitors, our review should stimulate further basic science and clinical studies in order to definitively understand the role of SGLT2 inhibitors in acute kidney injury.
The caveats of the non-adjudicated reporting of AKI in the trials notwithstanding, these data suggest that SGLT2 inhibitors may protect vulnerable patients with type 2 diabetes from AKI and that prospective studies to evaluate this additional aspect of kidney protection are warranted.
<b>Conclusion:</b> Lower risk of eGFR decrease over 40% and AKI-related hospitalization was found in all SGLT2 inhibitor users across the different CKD stages.
SGLT2 inhibitors have been associated with genital mycotic infections, increased risk of acute kidney injury, dehydration, orthostatic hypotension, and ketoacidosis.
This review focusses on the effects of SGLT2 inhibitors on the kidney and renal outcome: it briefly outlines renal glucose handling in diabetes and its role in glomerular hyperfiltration and renal hypoxia; describes how SGLT2 inhibitors induce an early, reversible reduction in glomerular filtration rate (GFR) and preserve GFR in the long-term in patients with T2DM; discusses whether the enhanced active transport in the renal outer medulla (OM) in response to SGLT2 inhibition is friend or foe; proposes how the blood pressure lowering and heart failure protective effect of SGLT2 inhibitors can be preserved in chronic kidney disease (CKD) despite attenuated antihyperglycemic effects; and examines whether SGLT2 inhibition enhances the incidence or severity of acute kidney injury (AKI).
Use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation (incidence rate 2.7 <i>v</i> 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 <i>v</i> 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 <i>v</i> 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 <i>v</i> 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 <i>v</i> 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 <i>v</i> 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 <i>v</i> 1.2, 1.16, 0.64 to 2.12).
The proportion of reports with ARF among reports with SGLT2 inhibitor was almost three-fold higher compared to reports without these drugs (ROR 2.88, 95% CI 2.71-3.05, p < 0.001).
The early onset of acute kidney injury events with SGLT2 inhibitors in postmarketing reports probably reflects the acute changes in eGFR attibutable to the known renal haemodynamic effects of SGLT2 inhibition.
We identified 377 SGLT2 inhibitor users and 377 nonusers in the Mount Sinai cohort, of whom 3.8 and 9.7%, respectively, had an AKI<sub>KDIGO</sub> event over a median follow-up time of 14 months.