Use of sodium–glucose cotransporter-2 inhibitors and risk of acute kidney injury in older adults with diabetes: a population-based cohort study

Iskander, Carina; Cherney, David Z.I.; Clemens, Kristin K.; Dixon, Stephanie N.; Harel, Ziv; Jeyakumar, Nivethika; McArthur, Eric; Muanda, Flory T.; Parikh, Chirag R.; Paterson, J. Michael; Tangri, Navdeep; Udell, Jacob A.; Wald, Ron; Garg, Amit X.

doi:10.1503/cmaj.191283

Cited by 60 publications

(64 citation statements)

References 56 publications

(63 reference statements)

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“…In individual CVOTs, AKI risk was either neutral or reduced with SGLT2 inhibitors, and in meta-analyses involving cardiorenal outcome studies, AKI risk was reduced by approximately 25% [ 7 – 10 , 17 , 18 ]. Similarly, in propensity-matched score analyses with electronic medical record data, AKI risk was lower with SGLT2 inhibitors than with other glucose-lowering therapies [ 29 ]. Consistent with this previous literature, our analysis found no indication of an increase in AKI risk with ertugliflozin.…”

Section: Discussionmentioning

confidence: 99%

Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

et al. 2021

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Aims/hypothesis In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration ClinicalTrials.gov NCT01986881 Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

et al. 2021

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“…Adverse event (AE) post-marketing reporting on AKI led the US Food and Drug Administration to issue warnings for SGLT2i to be used with caution in patients at risk of AKI. 9 However, data from clinical trials, 1,3,4,10 and large observational cohorts, [11][12][13][14] reported reduced AKI risk with SGLT2i.…”

Section: Introductionmentioning

confidence: 99%

Characterization and implications of the initial estimated glomerular filtration rate ‘dip’ upon sodium-glucose cotransporter-2 inhibition with empagliflozin in the EMPA-REG OUTCOME trial

Kraus

Weir

Bakris

et al. 2021

Kidney International

133

135

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“…Rampersad et al have therefore reported a robust clear clinical message about the kidney safety of SGLT2-inhibitor use in the real world, regardless of the definition of AKI, that is consistent with observations from clinical trials and other recent large retrospective propensity-matched cohort studies. 14 The consistency of this analysis is a major strength and should provide reassurance to both health care providers and patients.…”

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confidence: 98%

We Can Finally Stop Worrying About SGLT2 Inhibitors and Acute Kidney Injury

Sridhar

Cherney

2020

American Journal of Kidney Diseases

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Use of sodium–glucose cotransporter-2 inhibitors and risk of acute kidney injury in older adults with diabetes: a population-based cohort study

Cited by 60 publications

References 56 publications

Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

Characterization and implications of the initial estimated glomerular filtration rate ‘dip’ upon sodium-glucose cotransporter-2 inhibition with empagliflozin in the EMPA-REG OUTCOME trial

We Can Finally Stop Worrying About SGLT2 Inhibitors and Acute Kidney Injury

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