title: Long-term effects of addition of mineralocorticoid receptor antagonist to angiotensin II receptor blocker in patients with diabetic nephropathy: a randomized clinical trial.
abstract: BACKGROUND
  Addition of spironolactone (SPR) to angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) might provide antiproteinuric effects beyond what is gained by either medication alone. This study was designed to assess the long-term efficacy of SPR/ARB combination in comparison with the standard ACE/ARB regimen in diabetic nephropathy.
  
  
  METHODS
  In an open-label, parallel-group, single-center, randomized clinical trial (NCT01667614), 136 patients with diabetes and proteinuria, already treated with enalapril and losartan, were included. In 74 patients, ACE inhibitors were discontinued. After a wash-out period of 2 weeks, 25 mg SPR daily was initiated. The remainder of the patients (n = 62) received ACE inhibitors and ARBs as before. Patients were followed every 3 months for 18 months. During each visit, systolic and diastolic blood pressure (BP), urinary albumin excretion (UAE), serum creatinine, estimated glomerular filtration rate (eGFR) and serum potassium concentrations were determined.
  
  
  RESULTS
  After 18 months, three patients in the SPR/ARB group developed asymptomatic hyperkalemia. SPR/ARB significantly reduced both systolic and diastolic BP (P < 0.001 and 0.001, respectively). SPR/ARB decreased UAE by 46, 72 and 59% after 3, 12 and 18 months, respectively. Compared with the continuation regimen, SPR/ARB was superior in UAE reduction (P = 0.017 after 18 months), independent of BP change. In both groups, eGFR declined significantly over the trial course and the decline rate did not differ significantly between the two groups.
  
  
  CONCLUSIONS
  Addition of SPR to ARB provides added benefits with respect to BP control and proteinuria diminution. These antiproteinuric effects are not accompanied by prevention of eGFR loss compared with conventional therapy with ACE/ARB.
authors.affiliation: Endocrinology and Metabolism Research Center (EMRC), Vali-Asr Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Esteghamati
authors.forename: Sina
authors.initials: S
authors.lastname: Noshad
authors.forename: Sorour
authors.initials: S
authors.lastname: Jarrah
authors.forename: Mostafa
authors.initials: M
authors.lastname: Mousavizadeh
authors.forename: Seyed Hamid
authors.initials: SH
authors.lastname: Khoee
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Nakhjavani
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011379:Prognosis; D011507:Proteinuria / Q000188:drug therapy; D018161:Receptors, Mineralocorticoid / Q000737:chemistry; D013148:Spironolactone / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone
keywords: blood pressure control; diabetic nephropathy; glomerular filtration rate; mineralocorticoid receptor antagonist; urinary albumin excretion