title: Aliskiren combined with losartan in immunoglobulin A nephropathy: an open-labeled pilot study.
abstract: BACKGROUND
  Aliskiren is a relatively new oral direct renin inhibitor (DRI) that has been increasingly used for the treatment of diabetic nephropathy and hypertension. Its potential efficacy in nondiabetic chronic kidney diseases that are driven by renin-angiotensin system activation remains to be explored.
  
  
  METHODS
  From a teaching and regional hospital in Hong Kong between July 2009 and March 2010, patients with biopsy-proven immunoglobulin A nephropathy (IgAN) in whom the ratio of protein to creatinine, as measured in early morning urine samples, remained >113 mg/mmol (1000 mg/g), despite receiving the maximum recommended dose of losartan (100 mg daily) were recruited to receive additional DRI treatment. They were followed prospectively for 12 months with changes in proteinuria as the main outcome measure.
  
  
  RESULTS
  Twenty-five consecutive patients were enrolled. Treatment with aliskiren for 12 months reduced the mean urinary protein-to-creatinine ratio by 26.3% (95% confidence interval, 20.1-43.6; P = 0.001 versus baseline), with a reduction of ≥ 50% in 24% of patients. There were significant reductions in plasma renin activity (P < 0.0001) and serum interleukin-6 (P < 0.05) and transforming growth factor-β (P = 0.01) levels, compared with baseline. Two patients (8%) developed mild allergic reactions and six (24%) had transient hyperkalemia (K >5.5 mmol/L) during the study.
  
  
  CONCLUSIONS
  Aliskiren confers an antiproteinuric effect in IgAN patients with significant residual proteinuria, despite receiving the recommended renoprotective treatment. Further prospective randomized trials are warranted to examine its long-term renoprotective potential. This trial is registered with the ClinicalTrials.gov number NCT00922311.
authors.affiliation: Nephrology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
authors.forename: Sydney C W
authors.initials: SC
authors.lastname: Tang
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Wo Shing
authors.initials: WS
authors.lastname: Au
authors.forename: Maggie K M
authors.initials: MK
authors.lastname: Ma
authors.forename: Desmond Y H
authors.initials: DY
authors.lastname: Yap
authors.forename: Yiu Wing
authors.initials: YW
authors.lastname: Ho
authors.forename: Kar Neng
authors.initials: KN
authors.lastname: Lai
mesh_terms: D000328:Adult; D000577:Amides / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005650:Fumarates / Q000009:adverse effects / Q000627:therapeutic use*; D005922:Glomerulonephritis, IGA / Q000175:diagnosis* / Q000188:drug therapy*; D006723:Hong Kong; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D007677:Kidney Function Tests; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010865:Pilot Projects; D011446:Prospective Studies; D011507:Proteinuria / Q000517:prevention & control; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D016896:Treatment Outcome; D016482:Urinalysis
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; C446481:aliskiren; D019808:Losartan