title: Proteinuric renal disease in type 2 diabetes-is remission of proteinuria associated with improved mortality and morbidity?
abstract: OBJECTIVE
  Patients with type 2 diabetes and macroalbuminuria are at high risk for end stage renal disease (ESRD), cardiovascular disease and death, but remission of proteinuria may improve prognosis. We examine the effectiveness of currently recommended treatments on inducing remission of proteinuria, and on morbidity and mortality.
  
  
  METHODS
  Observational study of 78 patients with type 2 diabetes (46 male) with mean age (SD) of 61.5 (11) years, with a urinary albumin/creatinine ratio (ACR)≥50 mg/mmol. All were treated with agents blocking the renin-angiotensin system. Follow-up was from recognition of ACR ≥ 50 mg/mmol until death or March 2011 (median 6 years). Remission of proteinuria was defined as ≥70 % reduction from peak ACR, sustained for ≥1 year.
  
  
  RESULTS
  Only 22 of 78 patients (28%) achieved remission of proteinuria. Thirty-six (46%) had at least one major event (death, dialysis or cardiovascular). Remission of proteinuria was associated with lower incidence of ESRD/death (9% vs 36%; p=0.02) but cardiovascular events were not reduced (32% vs 30%). A third of patients had no retinopathy when albuminuria was first recognised, suggesting that non-diabetic renal pathologies were prominent. There was a significant interaction between the severity of diabetic retinopathy and remission of proteinuria on the risk of ESRD/death (p=0.0003).
  
  
  CONCLUSIONS
  Remission of proteinuria was achieved in only a third of patients despite efforts to achieve blood pressure targets <130/80 mmHg. Failure to attain remission of proteinuria was associated with increased risk of ESRD or death, a risk compounded by the presence of severe diabetic retinopathy.
authors.affiliation: Auckland Diabetes Centre, Green Lane Clinical Centre, Auckland, New Zealand. Electronic address: Jasmineta@adhb.govt.nz.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Tan
authors.affiliation: Auckland Diabetes Centre, Green Lane Clinical Centre, Auckland, New Zealand.
authors.forename: Rebekah
authors.initials: R
authors.lastname: Jaung
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
authors.forename: Gregory
authors.initials: G
authors.lastname: Gamble
authors.affiliation: Auckland Diabetes Centre, Green Lane Clinical Centre, Auckland, New Zealand; Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
authors.forename: Tim
authors.initials: T
authors.lastname: Cundy
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000150:complications; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000401:mortality*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000401:mortality / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000401:mortality / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D009520:New Zealand / Q000453:epidemiology; D011507:Proteinuria / Q000401:mortality / Q000503:physiopathology*; D012074:Remission Induction; D012084:Renin-Angiotensin System; D015996:Survival Rate
keywords: ACE inhibitor; ACEi; ACR; ARB; Albuminuria; Diabetic retinopathy; ESRD; End-stage renal disease; GFR; Mortality; RAAS; Renin–angiotensin system antagonist; albumin creatinine ratio; angiotensin II receptor blocker; end-stage renal disease; glomerular filtration rate; renin–angiotensin–aldosterone system