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.

Trial registration: ClinicalTrials.gov NCT00870493.

Figure 1. Summary of the study design and overall arrangement of treatment.

Figure 2. Serial change in proteinuria during the periods of aliskiren (closed circles) and placebo (open circles) treatment.

Error bars denote standard error of mean. Post-hoc comparisons were performed by paired Student’s t test: *p<0.05 and **p<0.0001 as compared to baseline level; ^$p<0.01 as compared to the period of placebo treatment. All P values were computed with Bonferroni adjustment for multiple comparisons.

Figure 3. Serial change in estimated glomerular filtration rate (eGFR) during the periods of aliskiren (closed circles) and placebo (open circles) treatment.

Error bars denote standard error of mean. Post-hoc comparisons were performed by paired Student’s t test: *p<0.05 as compared to baseline level. All P values were computed with Bonferroni adjustment for multiple comparisons.

Figure 4. Serial change in systolic and diastolic blood pressure (BP) during the periods of aliskiren (closed circles) and placebo (open circles) treatment.

Error bars denote standard error of mean. Post-hoc comparisons were performed by paired Student’s t test: *p<0.0001 as compared to baseline level; ^$p<0.05 as compared to the period of placebo treatment. All P values were computed with Bonferroni adjustment for multiple comparisons.

Figure 5. Serial change in plasma renin activity during the periods of aliskiren (closed circles) and placebo (open circles) treatment.

Error bars denote standard error of mean. Post-hoc comparisons were performed by paired Student’s t test: *p<0.0001 as compared to baseline level; ^$p<0.0001 as compared to the period of placebo treatment. All P values were computed with Bonferroni adjustment for multiple comparisons.

Figure 6. Serial change in serum potassium level during the periods of aliskiren (closed circles) and placebo (open circles) treatment.

Error bars denote standard error of mean. Post-hoc comparisons were performed by paired Student’s t test: *p<0.001 as compared to baseline level; ^$p<0.001 as compared to the period of placebo treatment. All P values were computed with Bonferroni adjustment for multiple comparisons.