Renal and cardiovascular effects of SGLT2 inhibitors among hypertensive patients with chronic kidney disease: A systematic review and meta-analysis.

Abstract

<h4>Background</h4>Chronic kidney disease (CKD) is frequently complicated by hypertension, a dual contributor to disease progression and cardiovascular risk. Despite standard therapy with renin-angiotensin-aldosterone system inhibitors, residual risk remains high. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a novel therapy with proven renal and cardiovascular benefits, but their effects in hypertensive CKD patients remain less well defined.<h4>Methods</h4>We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated SGLT2 inhibitors in CKD patients with baseline systolic blood pressure ≥140 mmHg or renovascular disease. PubMed, Embase, and Cochrane Library were searched from inception to August 2024. Eligible RCTs compared an SGLT2 inhibitor versus placebo and reported outcomes in hypertensive subgroups. Primary outcome was a composite of kidney failure, sustained decline in estimated glomerular filtration rate (eGFR ≥40-50 %), or cardiovascular death. Secondary outcomes included kidney-specific endpoints, cardiovascular composite outcomes, and serious adverse events (SAEs). Pooled odds ratios (ORs) were calculated using random-effects models.<h4>Results</h4>Three RCTs were included: CREDENCE (canagliflozin), DAPA-CKD (dapagliflozin), and EMPA-KIDNEY (empagliflozin), encompassing 5436 hypertensive participants. For the primary outcome, SGLT2 inhibitors reduced risk compared with placebo (OR 0.76, 95 % CI 0.65-0.88). Kidney outcomes showed consistent benefit (OR 0.70, 95 % CI 0.58-0.85). Cardiovascular events were modestly reduced (OR 0.79, 95 % CI 0.64-0.97). SAEs were slightly lower with SGLT2 inhibitors (OR 0.85, 95 % CI 0.74-0.96). Overall certainty of evidence was graded as moderate.<h4>Conclusions</h4>Among hypertensive patients with CKD, SGLT2 inhibitors significantly reduce renal disease progression and cardiovascular events while maintaining favorable safety. These findings support their integration into standard therapy for this high-risk population.