title: Beneficial long-term effect of aldosterone antagonist added to a traditional blockade of the renin-angiotensin-aldosterone system among patients with obesity and proteinuria.
abstract: BACKGROUND
  Over the past decade, obesity has become a risk factor for developing chronic kidney disease. Proteinuria is known to be an independent determinant of the progression of chronic kidney disease, and adipose tissue is a recognized source of components of the renin-angiotensin-aldosterone system (RAAS). Recent studies have shown that plasma aldosterone levels are disproportionately higher in patients with obesity. Drugs that block the RAAS are unable to inhibit aldosterone in the long term. The aim of our study was to analyze the renoprotective effect of an aldosterone antagonist in combination with RAAS blockers in patients with obesity and proteinuric nephropathy.
  
  
  METHODS
  This study is a substudy of previously published study on the renoprotective effect of mineralocorticoid receptor blockers in patients with proteinuric nephropathies. Patients with proteinuria levels >1g/24h who were taking spironolactone and were being treated with other RAAS blockers were divided according to body mass index (BMI) into an obesity group (BMI ≥30kg/m2) and a control group.
  
  
  RESULTS
  Seventy-one patients were included in the study, with a mean age of 56.7±15.1 years. More than 50% of the patients in both groups had diabetes. Thirty-two patients were included in the obesity group and 39 were included in the control group. There were no significant differences in renal function, proteinuria, blood pressure, serum potassium levels and the percentage of RAAS blockers in both groups. After a follow-up of 28.9 (14-84) months, there was a 59.4% reduction in proteinuria in the obesity group (2.8±2.1 vs. 1.3±1.6g/24h, p<.05). The reduction in proteinuria was greater than 50% in 22 (68.8%) cases, and the mean blood pressure showed a significant decrease (from 100.6±9 to 92.1±7.4mm Hg, p<.05). The control group showed a 69.6% reduction in proteinuria (1.9±1.4 to 0.8±0.5, p<0.05). The reduction of proteinuria was higher than 50% in 22 (68.8%) cases in obese patients and in 33 (84.6%) cases in non-obese group. Renal function remained stable in both groups during the follow-up. Nine patients (28.1%) in the obesity group experienced gynecomastia. The incidence of hyperkalemia was similar for the 2 groups (6.3%).
  
  
  CONCLUSIONS
  Aldosterone antagonist treatment in obese patients with proteinuric nephropathies induces a drastic and sustained reduction in proteinuria but not more than the non-obese group. There was a trend toward slowing progression of renal failure with few adverse events.
authors.affiliation: Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain. Electronic address: emorales.hdoc@salud.madrid.org.
authors.forename: Enrique
authors.initials: E
authors.lastname: Morales
authors.affiliation: Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gutiérrez
authors.affiliation: Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Jara
authors.initials: J
authors.lastname: Caro
authors.affiliation: Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Sevillano
authors.affiliation: Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rojas-Rivera
authors.affiliation: Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
mesh_terms: D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015992:Body Mass Index; D048909:Diabetes Complications / Q000188:drug therapy; D018450:Disease Progression; D057915:Drug Substitution; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077545:Eplerenone; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications*; D011446:Prospective Studies; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy*; D051437:Renal Insufficiency / Q000209:etiology / Q000517:prevention & control; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013148:Spironolactone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone
keywords: Aldosterone antagonist; Antagonista de la aldosterona; Nefropatía; Nephropathy; Obesidad; Obesity; Proteinuria