Abstract
Introduction: The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials. However, the magnitude of renal benefits for CKD patients with different baseline features and underlying diseases remains unclear.Method: We systematically searched the Embase, PubMed, Web of Science, and Cochrane library databases from inception to April 15, 2021 to identify eligible trials. The primary outcome was a composite of worsening kidney function, end-stage kidney disease (ESKD), or renal death. Efficacy and safety outcomes were stratified by baseline features, such as type 2 diabetes, heart failure, atherosclerotic cardiovascular disease, proteinuria, and renal function.Results: A total of nine studies were included. These studies included 25,749 patients with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2 and 12,863 patients with urine albumin-to-creatinine ratio (UACR) >300 mg/g. SGLT2 inhibitors reduced the risk of the primary renal outcome by 30% in patients with eGFR<60 mL/min/1.73 m2 (HR 0.70, [95% CI 0.58–0.83], I2 = 0.00%) and by 43% in patients with UACR > 300 mg/g (HR 0.57, [95% CI 0.48–0.67], I2 = 16.59%). A similar benefit was observed in CKD patients with type 2 diabetes. SGLT2 inhibitors had no clear effects on renal outcomes in patients with eGFR<60 mL/min/1.73 m2 combined with atherosclerotic cardiovascular disease (HR 0.74, [95% CI 0.51–1.06], I2 = 0.00%). However, they reduced the risk of major renal outcomes by 46% (HR 0.54, [95% CI 0.38–0.76], I2 = 0.00%) in patients with atherosclerotic cardiovascular disease and macroalbuminuria (defined as UACR > 300 mg/g). SGLT2 inhibitors did not significantly reduce the risk of major renal outcomes in CKD patients with heart failure (eGFR<60 mL/min/1.73 m2: HR 0.81, [95% CI 0.47–1.38], I2 = 0.00%; UACR > 300 mg/g: HR 0.66, [95% CI 0.41–1.07], I2 = 0.00%). SGLT2 inhibitors showed consistent renal benefits across different levels of eGFR (P interaction = 0.48).Conclusion: SGLT2 inhibitors significantly reduced the risk of the primary outcome in CKD patients. However, for patients with different features and underlying diseases, there exists differences in the renal protective effect.
Highlights
The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials
Combined with the results in patients with CKD complicated with heart failure, we propose that SGLT2 inhibitors may not provide clinically relevant renal benefits in patients with CKD complicated with CVD, especially those with estimated glomerular filtration rate (eGFR)
SGLT2 inhibitors significantly reduced the risk of primary renal outcomes in patients with CKD, and this benefit was consistent across the spectrum of different levels of eGFR
Summary
The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on renal outcomes in patients with chronic kidney disease (CKD) were initially demonstrated in recent trials. The magnitude of renal benefits for CKD patients with different baseline features and underlying diseases remains unclear. Chronic kidney disease (CKD) has become a major global public health problem that imposes a heavy burden on families and society. Within the past two decades, the only approved renoprotective therapy for CKD patients, notably those with type 2 diabetes, has been reninangiotensin system (RAS) blockers [2]. It is encouraging that in recent years, more and more novel drugs have been developed that provide renoprotection for CKD patients [3,4,5], including sodium-glucose cotransporter-2 (SGLT2) inhibitors. The emergence of SGLT2 inhibitors has resulted in promising new options for renoprotection
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