Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) is a long-term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of the Kidney Disease Improving Global Outcomes (KDIGO) classifications. Early recognition and management of CKD affords the opportunity to prepare for progressive kidney impairment and impending kidney replacement therapy and for intervention to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosterone system. Beneficial effects of ACEi and ARB on kidney outcomes and survival in people with a wide range of severity of kidney impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain. This is an update of a review that was last published in 2011. OBJECTIVES: To evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD who do not have diabetes mellitus (DM). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 6 July 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and Embase, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have DM were selected for inclusion. Only studies of at least four weeks duration were selected. Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS: , 95% CI 3.03 to 6.97), presence of proteinuria (MD -0.65 g/24 hours, 95% CI -0.78 to -0.52), systolic blood pressure (MD -0.80 mm Hg, 95% CI -3.89 to 2.29), or diastolic blood pressure (MD -1.10 mm Hg, 95% CI -3.29 to 1.09) because the certainty of the evidence is very low. It is uncertain whether ACEi (enalapril 20 mg, perindopril 2 mg or trandolapril 1 mg) compared to ARB (olmesartan 20 mg, losartan 25 mg or candesartan 4 mg) (1 study, 26 participants) reduces: proteinuria (MD -0.40, 95% CI -0.60 to -0.20), systolic blood pressure (MD -3.00 mm Hg, 95% CI -6.08 to 0.08) or diastolic blood pressure (MD -1.00 mm Hg, 95% CI -3.31 to 1.31) because the certainty of the evidence is very low. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have DM. The available evidence is overall of very low certainty and high risk of bias. We have identified an area of large uncertainty for a group of patients who account for most of those diagnosed as having CKD.