Sodium–glucose cotransporter 2 inhibitor‐induced reduction in the mean arterial pressure improved renal composite outcomes in type 2 diabetes mellitus patients with chronic kidney disease: A propensity score‐matched model analysis in Japan

Abstract

Aims/Introduction Large‐scale clinical trials have reported that, in patients with type 2 diabetes mellitus, sodium–glucose cotransporter 2 (SGLT2) inhibitor treatment affords favorable renal outcomes; the underlying mechanisms, however, remain unclear. Thus, this study investigated how SGLT2 inhibitor‐induced changes in the mean arterial pressure (MAP; denoted as ΔMAP) are associated with renal outcomes in type 2 diabetes mellitus patients with chronic kidney disease (CKD). Materials and Methods We retrospectively assessed the data of 624 Japanese type 2 diabetes mellitus patients with CKD who had been using SGLT2 inhibitors for >1 year. For propensity score matching (1:1 nearest neighbor match, with caliper value = 0.053, no replacement), patients were categorized into two groups based on the ΔMAP (>−4 mmHg [n = 329] and ≤−4.0 mmHg [n = 295]). Composite albuminuria progression or a ≥15% annual reduction in the estimated glomerular filtration rate was regarded as the end‐point. Results Per group, 173 propensity‐matched patients were compared. Patients with ΔMAP ≤−4 mmHg had a significantly lower incidence of composite renal outcomes than those with ΔMAP ≥−4 mmHg (5.8% [n = 10] vs 15.6% [n = 27], P = 0.003). Although the between‐group differences in the estimated glomerular filtration rates were non‐significant, patients with a ΔMAP ≤−4 mmHg had significantly larger reductions in the logarithmic urine albumin‐to‐creatinine ratio (P = 0.005). Conclusions The degree of blood pressure reduction after SGLT2 inhibitor treatment influenced renal composite outcomes in Japanese type 2 diabetes mellitus patients with CKD, confirming the importance of blood pressure management in type 2 diabetes mellitus patients with CKD, even when they are under SGLT2 inhibitor treatment.

Polypharmacy influences the renal composite outcome in patients treated with sodium‐glucose cotransporter 2 inhibitors

“… 17 , 18 , 19 , 20 However, the appropriate end points are not completely agreed upon and should be chosen depending on the study design or participants. According to our previous study, 5 , 6 we defined the renal composite outcome as ACR progression, a greater than 15% annual decrease in the eGFR, or both.…”

“…If this is true, then GPs must address polypharmacy, for example, by reducing the number of concomitant medications via better lifestyle management. Our interest is not only in the effect of polypharmacy; we have already analyzed the conditions under which the renoprotective effect of an SGLT2i is deteriorated (e.g., some levels of blood pressure management after SGLT2i treatment, 5 , 6 differences among dissimilar types of SGLT2i treatments, 7 and effects of an SGLT2i with or without dipeptidyl peptidase 4 (DPP4) inhibitors during SGLT2i treatment (Journal of Diabetes Research, in press).…”

The roles of sodium and volume overload on hypertension in chronic kidney disease

“…Among them, sodium excretion in the proximal tubule followed by increased sodium delivery to the macula densa and tubuloglomerular feedback results in a short-term increase in the excretion of renal sodium [ 50 ]. BP reduction as the one of the important mechanisms of cardiorenal protection has been proven in CKD patients [ 51 , 52 ]. Although precise interactions or differential effects between loop diuretics and SGLT2I require further studies or analyses, it was reported in terms of heart failure that SGLT2I prevents the increase of the dose of loop diuretics, and that it can overcome the resistance of loop diuretics [ 53 ].…”

The combination of dapagliflozin and statins ameliorates renal injury through attenuating the activation of inflammasome‐mediated autophagy in insulin‐resistant rats

“…[12] In addition, preclinical and animal studies documented the secondary effects of glycemic control by an SGLT2 inhibitor, such as improved mean arterial blood pressure, pancreatic endoplasmic reticulum (ER) stress, hepatic steatosis, and injury. [13][14][15] However, the effects of combination therapy of dapagliflozin with atorvastatin focusing on kidney injury, renal autophagy, and inflammasome activation in insulin-resistant rat models have not been clarified. This study aimed to investigate the effects of dapagliflozin monotherapy or combination with atorvastatin on kidney injury associated with autophagy impairment and inflammasome activation induced by high-fat high-fructose diet feds rats (HFF) consumption in insulin-resistant rats.…”