title: Antihypertensive agents for preventing diabetic kidney disease.
abstract: BACKGROUND
  Various blood pressure-lowering agents, and particularly inhibitors of the renin-angiotensin system (RAS), are widely used for people with diabetes to prevent the onset of diabetic kidney disease (DKD) and adverse cardiovascular outcomes. This is an update of a Cochrane review first published in 2003 and updated in 2005.
  
  
  OBJECTIVE
  This systematic review aimed to assess the benefits and harms of blood pressure lowering agents in people with diabetes mellitus and a normal amount of albumin in the urine (normoalbuminuria).
  
  
  METHODS
  In January 2011 we searched the Cochrane Renal Group's Specialised Register through contact with the Trials Search Co-ordinator.
  
  
  METHODS
  Randomised controlled trials (RCTs) comparing any antihypertensive agent with placebo or another agent in hypertensive or normotensive patients with diabetes and no kidney disease (albumin excretion rate < 30 mg/d) were included.
  
  
  METHODS
  Two investigators independently extracted data on kidney and other patient-relevant outcomes (all-cause mortality and serious cardiovascular events), and assessed study quality. Analysis was by a random effects model was applied to analyse results which were expressed as risk ratio (RR) and 95% confidence intervals (CI).
  
  
  RESULTS
  We identified 26 studies that enrolling 61,264 participants. Angiotensin-converting enzyme inhibitors (ACEi) reduced the risk of new onset of microalbuminuria, macroalbuminuria or both when compared to placebo (8 studies, 11,906 patients: RR 0.71, 95% CI 0.56 to 0.89), with similar benefits in people with and without hypertension (P = 0.74), and when compared to calcium channel blockers (5 studies, 1253 participants: RR 0.60, 95% CI 0.42 to 0.85). ACEi reduced the risk of death when compared to placebo (6 studies, 11,350 participants: RR 0.84, 95% CI 0.73 to 0.97). No effect was observed for angiotensin receptor blockers (ARB) when compared to placebo for new microalbuminuria, macroalbuminuria or both (5 studies, 7653 participants: RR 0.90, 95% CI 0.68 to 1.19) or death (5 studies, 7653 participants: RR 1.12, 95% CI 0.88 to 1.41); however, meta-regression suggested possible benefits from ARB for preventing kidney disease in high risk patients. There was a trend towards benefit from use of combined ACEi and ARB for prevention of DKD compared with ACEi alone (2 studies, 4171 participants: RR 0.88, 95% CI 0.78 to 1.00).The risk of cough was significantly increased with ACEi when compared to placebo (6 studies, 11,791 patients: RR 1.84, 95% CI 1.24 to 2.72), however there was no significant difference in the risk of headache or hyperkalaemia. There was no significant difference in the risk of cough, headache or hyperkalaemia when ARB was to placebo. On average risk of bias was judged to be either low (27% to 69%) or unclear (i.e. no information available) (8% to 73%). Blinding of participants, incomplete outcome data and selective reporting were judged to be high in 23%, 31% and 31% of studies, respectively.
  
  
  CONCLUSIONS
  ACEi were found to prevent new onset DKD and death in normoalbuminuric people with diabetes, and could therefore be used in this population. More data are needed to clarify the role of ARB and other drug classes in preventing DKD.
authors.affiliation: Renal andMetabolic Division, The George Institute for Global Health, Camperdown, Australia.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Lv
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.forename: Celine V
authors.initials: CV
authors.lastname: Foote
authors.forename: Maria E
authors.initials: ME
authors.lastname: Craig
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.forename: Giovanni F M
authors.initials: GF
authors.lastname: Strippoli
mesh_terms: D000419:Albuminuria / Q000517:prevention & control; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers