The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy - A Randomized Cross-Over Study

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.