Effects of ACE Inhibitors and Angiotensin Receptor Blockers in Normotensive Patients with Diabetic Kidney Disease

Abstract

The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in reducing the progression of albuminuria and risk of cardiovascular events in hypertensive patients with diabetic kidney disease (DKD) is well-documented. However, the efficacy and safety of these agents in normotensive patients with DKD are still controversial. MEDLINE, Embase, and Cochrane Library were searched for relevant random controlled trials. The odd risk (OR) reductions were calculated with a random-effects model. Decrease in albuminuria, changes in eGFR, major cardiovascular events, and drug-related adverse events were analyzed. Thirteen RCTs including 1282 patients were retrieved. Compared with placebo or other active agent groups, ACEIs or ARBs significantly decreased albuminuria (MD –80.28 mg/d, 95% CI –104.79 mg/d to –55.77 mg/d), and the efficacy is independent of changes in blood pressure and systolic blood pressure at baseline. The result of subanalysis showed the declining of albuminuria was more significantly in normotensive DKD patients with 2DM (p=0.005). No significant differences were found with regard to the declining of evaluated glomerular filtration rate (eGFR) (MD –0.29 ml/min/1.73 m2, 95% CI –2.99 to 2.41 ml/min/1.73 m2). There were no significant differences in the side effect of the drugs such as hypotension and hyperkalemia. This meta-analysis demonstrated that ACEIs or ARBs can decrease albuminuria to varying degree in normotensive patients with DKD, and better response occurred in patients with 2DM.

Diabetic kidney disease in type 2 diabetes: a review of pathogenic mechanisms, patient-related factors and therapeutic options

“…While the use of ACEis and ARBs in delaying the progression of DKD in hypertensive T2DM patients is well established, the use of these agents in normotensive patients remains controversial. A recent meta-analysis investigated the efficacy and safety of these therapeutic agents in normotensive patients with DKD and found they significantly reduced albuminuria independent of changes to blood pressure (He et al, 2020). There were no significant differences in adverse effect profiles of the treatments (hyperkalaemia and hypotension) and response to treatment was superior in normotensive people living with T2DM than in normotensive patients with DKD (He et al, 2020).…”

“…A recent meta-analysis investigated the efficacy and safety of these therapeutic agents in normotensive patients with DKD and found they significantly reduced albuminuria independent of changes to blood pressure (He et al, 2020). There were no significant differences in adverse effect profiles of the treatments (hyperkalaemia and hypotension) and response to treatment was superior in normotensive people living with T2DM than in normotensive patients with DKD (He et al, 2020). Conclusively, BP management does affect the development and progression of DKD and effective management is crucial in improving prognosis (McGrath & Edi, 2019).…”

Prediction models for risk of diabetic kidney disease in Chinese patients with type 2 diabetes mellitus

“…Of which, there are several medications that can improve cardiac and renal outcomes. BP lowering with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are proven to slow down the progression of DKD [ 5 , 6 ]. Mineralocorticoid receptor antagonists (MRAs) have efficacy in resistant hypertension, reducing albuminuria and DKD progression, as well as reduction of cardiovascular disease (CVD) and heart failure [ 7 , 8 ].…”

Lipidomic Analysis Reveals the Protection Mechanism of GLP-1 Analogue Dulaglutide on High-Fat Diet-Induced Chronic Kidney Disease in Mice

“…Unfortunately, patients treated with RAS inhibitors have a definite increase in the chances of hyperkalemia and hypotension and still have a high risk of ESRD ( Burns and Cherney, 2019 ; Zhang et al, 2020 ). The efficacy and safety of ACE inhibitors and ARB in DKD patients are still controversial ( Wang et al, 2018 ; He et al, 2020 ). Because DKD is associated with a widely heterogeneous range of pathological features, such as the progression of DKD, which can be either classical albuminuric or new non-albuminuric pathways ( Pugliese et al, 2020 ), different therapeutic strategies for the treatment of DKD are required.…”