To the editor:
We have read with immense interest the review article by Yau-K et al.1 titled “Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations”; a revision that evaluates the practical aspects related to the prescription of these medications, dose adjustments, having in mind special situations such as volume status and adverse effects. Reviewing the recommendations thoroughly, we would like to consider several aspects of importance.
In the subtitle “Consideration of Diuretic Effect and Volume Status,” the authors recommend that euvolemic patients with previous loop diuretic therapy should have their concomitant SGLT-2 dose reduced. Whereas this is a logical recommendation based on the diuretic effects of SGLT-2 inhibitors, in a secondary analysis of the dapagliflozin and prevention of adverse outcomes in CKD, the effect of dapagliflozin versus placebo was assessed according to baseline diuretic and aldosterone receptor antagonists use.2 It concluded that dapagliflozin was well tolerated and the safety profile was consistent between the treatment groups when stratified by baseline diuretic and aldosterone receptor antagonists use. In addition, in this analysis, the renal composite outcome (sustained ≥50% estimated glomerular filtration rate decline, end stage kidney disease, renal death) benefit with dapagliflozin was observed regardless of baseline diuretic and aldosterone receptor antagonists use. In summary, it is a logical recommendation, but without strong evidence to support it.
On the other hand, in the subtitle “stage 4 CKD,” it is mentioned that the published evidence of SGLT-2 inhibitors was mainly derived from the dapagliflozin and prevention of adverse outcomes in CKD trial, which included patients with estimated glomerular filtration rate down to 25 ml/min per 1.72 m2. In addition, the EMPEROR-preserved and EMPEROR-reduced trials of empagliflozin in heart failure included patients with estimated glomerular filtration rate greater than 20 ml/min per 1.72 m2 give complementary information in renal outcomes. Though it was not the primary outcome, it was included in the secondary analyses.3,4
Lastly, the revision also mentions the combination of SGLT-2 inhibitors with GLP-1 agonists. They refer to the limited evidence of this combination of drugs from the DURATION-8, AWARD-10 and SUSTAIN-9 studies.5, 6, 7 It is worth mentioning that these studies had the primary objective to evaluate safety and efficacy, not the renal and cardiovascular outcomes, because they did not include patients with chronic kidney disease with baseline estimated glomerular filtration rate greater than 60 ml/min per 1.72 m2.
References
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