Aliskiren combined with losartan in immunoglobulin A nephropathy: an open-labeled pilot study

Abstract

INTRODUCTION AND AIMS: 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 IgA nephropathy (IgAN) in whom the ratio of protein to creatinine, as measured in early morning urine samples, remained > 113 mg/mmol (1,000 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 6 months with changes in proteinuria and serum/urine cytokines as the main outcome measures. RESULTS: Twenty-five consecutive patients were enrolled. Treatment with aliskiren for 6 months reduced the mean urinary protein-to-creatinine ratio reduced by 22% (95% CI, 9.1 to 36.7; P=0.029 vs baseline), with a reduction of 50% or more in 35% of patients. There were significant reductions in plasma renin activity (P<0.0001), and serum interleukin-6 (P<0.05) and transforming growth factor-b (P=0.01) levels, compared with baseline. Two patients (8%) developed mild allergic reactions and 6 (24%) had transient hyperkalemia (K>5.5 mmol/l) during the study. CONCLUSIONS: Aliskiren may have renoprotective effects in IgAN patients with persistent proteinuria who are receiving the recommended renoprotective treatment. Further prospective, randomized trials are warranted. This trial is registered with the ClinicalTrials.gov number NCT00922311.