Cardiorenal outcomes associated with sodium-glucose co-transporter-2 inhibitors in chronic kidney disease stage 5 (CKD V): A propensity score-matched analysis

Background: There remains a paucity of data regarding the cardio-renal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease stage 5 (CKD V) based on major clinical trials.

Objective: This retrospective study aimed to identify potential cardiovascular and renal outcomes associated with SGLT2i use in CKD V patients.

Methods: We queried the TriNetX Global collaborative network from Jan 2014 - Aug 2023 for patients ≥18 years diagnosed with CKD V but not on dialysis. Patients were stratified based on SGLT2i use. Propensity score matching for sociodemographics, comorbidities, and medication use resulted in 3465 patients in each cohort. The primary outcome was a composite of all-cause mortality, progression to end-stage renal disease (ESRD), or heart failure (HF). Secondary outcomes were ESRD, heart failure, all-cause mortality, acute myocardial infarction (AMI), ischemic stroke, cardiac arrest, hypertensive urgency, and hypertensive crisis. Cox proportional HRs were used to compare outcomes over a 5-year follow-up period.

Results: The SGLT2i cohort was associated with a significantly lower risk of the primary composite outcome (HR 0.644; 95 % CI: 0.601-0.733, p < 0.0001). SGLT2i use was also associated with lower risks of some secondary outcomes including all-cause mortality (HR 0.649; 0.587-0.717, p < 0.0001), ESRD (HR 0.597; 0.547-0.652, p < 0.0001), heart failure (HR 0.726; 0.625-0.844, p < 0.0001), development of AMI (0.649; 0.542-0.776, p < 0.0001), cardiac arrest (HR 0.595; 0.462-0.766, p < 0.0001), hypertensive urgency (HR 0.578; 0.3451-0.740, p < 0.0001), and hypertensive crisis (HR 0.603; 0.481-0.755, p < 0.0001).

Conclusion: Among CKD V patients, SGLT2i was associated with a significantly slowed progression of CKD to ESRD and reduced cardiac morbidity and mortality.