title: The safety and short-term efficacy of aliskiren in the treatment of immunoglobulin a nephropathy--a randomized cross-over study.
abstract: BACKGROUND
  Laboratory research and previous study suggest that aliskiren, a direct renin inhibitor, has anti-proteinuric effects. We conducted a randomized crossover study to evaluate the anti-proteinuric effect of aliskiren in patients with immunoglobulin A (IgA) nephropathy.
  
  
  METHODS
  We studied 22 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Patients were randomized to either oral aliskiren 300 mg/day or placebo for 16 weeks and then crossed over to the other treatment arm after a washout period. Proteinuria, estimated glomerular filtration rate (eGFR), blood pressure, and serum potassium were monitored.
  
  
  RESULTS
  After aliskiren treatment, there was a significant reduction in proteinuria in 4 weeks (1.76±0.95 to 1.03±0.69 g:g-Cr, p<0.0001), which remained at a low level throughout the treatment period. There was a significant difference in proteinuria between the aliskiren and placebo groups from 4 to 16 weeks after treatment (p<0.01 for all comparisons). After aliskiren treatment, there were modest but statistically significant reductions in eGFR (57.2±29.1 to 54.8±29.3 ml/min/1.73 m(2), p = 0.013) and diastolic blood pressure (72.6±12.3 to 66.2±11.2 mmHg, p<0.0001). None of the patient developed severe hyperkalemia (serum potassium ≥6.0 mmol/l) during the study period.
  
  
  CONCLUSIONS
  Aliskiren has anti-proteinuric effect in patients with IgA nephropathy and persistent proteinuria despite ACE inhibitor or ARB. Further studies are needed to confirm the renal protecting effect of direct renin inhibition in chronic proteinuric kidney diseases.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00870493.
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China. ccszeto@cuhk.edu.hk
authors.forename: Cheuk-Chun
authors.initials: CC
authors.lastname: Szeto
authors.forename: Bonnie Ching-Ha
authors.initials: BC
authors.lastname: Kwan
authors.forename: Kai-Ming
authors.initials: KM
authors.lastname: Chow
authors.forename: Chi-Bon
authors.initials: CB
authors.lastname: Leung
authors.forename: Philip Kam-Tao
authors.initials: PK
authors.lastname: Li
mesh_terms: D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D012083:Renin / Q000097:blood; D016896:Treatment Outcome; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren