title: Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy.
abstract: OBJECTIVE
  Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria in diabetic nephropathy (DN). Some studies have suggested that dual blockade of the renin-angiotensin system provides additive benefits in DN but others showed increased adverse events. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy for DN.
  
  
  METHODS
  Studies were identified by searching MEDLINE, EMBASE, PubMed, and CNKI. All trials involved ACEI + ARB (combination therapy), and ACEI or ARB alone (monotherapy) for DN. The outcomes measured were urinary total proteinuria (UTP), urinary albumin excretion rate (UAER), serum creatinine, glomerular filtration rate (GFR), end-stage renal disease (ESRD), hyperkalemia, hypotension, and acute kidney injury (AKI).
  
  
  RESULTS
  In the 32 included trials, 2596 patients received combination therapy and 3947 received monotherapy. UTP and UAER were significantly reduced by combined treatment compared with monotherapy. It was notable that low doses of combination therapy reduced UTP more than high doses. Serum creatinine, GFR, and ESRD were not significantly different between the two groups. In severe DN, the occurrence of hyperkalemia and AKI were higher with combination therapy. However, in mild DN, the prevalence of hyperkalemia and AKI were the same in both the groups. In mild DN, the occurrence of hypotension was higher with combination therapy; however, in severe DN, it was not different between the two groups.
  
  
  CONCLUSIONS
  Our meta-analysis suggests that combination therapy can be used on DN with proteinuria, but should be used with caution in those with decreased renal function, especially with severe renal failure.
authors.affiliation: Department of Nephrology and Rheumatology and.
authors.forename: Feifeng
authors.initials: F
authors.lastname: Ren
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Yin
authors.initials: Y
authors.lastname: Cai
authors.forename: Xin
authors.initials: X
authors.lastname: Yuan
authors.forename: Wenhan
authors.initials: W
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Yaning
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006801:Humans; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: ACEI; ARB; combined treatment; diabetic nephropathy; meta-analysis