In this editorial, we update the different postulated mechanisms involved in the cardiorenal protection afforded by SGLT2 inhibition in chronic kidney disease.
However, the use of drugs that target specific pathways to delay or halt CKD progression, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors is limited in clinical practice.
Three, multicentre, large-scale, randomized, placebo-controlled trials of cardiovascular outcomes with sodium-glucose co-transporter-2 (SGLT2) inhibitors have each shown substantial reductions in rates of hospitalization for heart failure and progression of chronic kidney disease in people with type 2 diabetes.
This study confirmed that the beneficial renal effects of SGLT2 inhibitor in Japanese type 2 diabetes mellitus patients with chronic kidney disease, similar to those reported in large-scale clinical trials conducted in Western countries.
This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of SGLT-2 inhibitors and GLP-1 analogues, analyses the potential mechanisms involved in these actions and discusses their place in the treatment of patients with CKD and DM.
However, in cardiovascular outcome trials, and a dedicated renal outcome trial, cardiovascular and renal benefits were seen in participants with CKD suggesting that mechanisms underlying the cardiovascular and renal benefits of SGLT2 inhibitors are likely largely independent of the glucose-lowering action of these agents.
These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes.
Baseline mean (SD) eGFR was higher among the SGLT2-i group compared with the DPP-4i group (88.3 [17.4] and 82.8 [23.7], respectively) but were similar when stratifying by chronic kidney disease (CKD) stages.
The blood pressure-lowering effect of SGLT2 inhibitors is maintained in people with CKD and could further contribute to reduced renal burden, as well as potentially offering synergistic effects with antihypertensive therapies in these patients.
There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes.
<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.
Based on such evidence, the recent guidelines for the management of type 2 diabetes now suggest that SGLT-2 inhibitors should be preferred among oral agents in combination with metformin, in patients at increased cardiovascular risk, chronic kidney disease or heart failure.
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have become the best choice of second-line oral antidiabetic drugs for patients with heart or chronic kidney disease.
This raises the possibility that the lowering of uric acid by SGLT2 inhibition may assist in reducing adverse CV events and slowing progression of CKD in type 2 diabetes.
Relation between Blood Pressure Management and Renal Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic Patients with Chronic Kidney Disease.
The current overview article summarises these aspects and discusses future treatment strategies with SGLT2 inhibitors in diabetic and non-diabetic individuals with chronic kidney disease, liver disease and heart failure.
These effects may contribute to the protective effects of SGLT2 inhibitors on blood pressure and heart failure observed in diabetic patients with chronic kidney diseases.
These data indicate that chronic treatment with an SGLT2 inhibitor does not activate the systemic and intrarenal RAS in subjects with non-diabetic CKD.
SGLT2 inhibitors display renoprotective effects in diabetic kidney disease, which creates a rationale for testing the therapeutic potential of this drug class in nondiabetic chronic kidney disease.
In this issue of Kidney International, Zhang et al. report renoprotective effects with the sodium glucose cotransporter 2 inhibitor lusogliflozin in an ischemia-reperfusion injury model under nondiabetic conditions, thereby providing important mechanistic insights into the use of these agents in chronic kidney disease.