A clinical trial comparing aliskiren with enalapril for the treatment of C3 glomerulopathy

Abstract

Abstract Introduction To date there is no established, effective treatment for C3 glomerulopathy, encompassing both Dense Deposit Disease and C3 glomerulonephritis. We have previously reported that renin mediates complement activation by cleaving C3 and found that the direct renin inhibitor aliskiren blocked complement activation by renin and inhibited complement activation systemically and in the kidneys in three patients with Dense Deposit Disease. Theoretically enalapril should increase renin without blocking its effect and therefore we will conduct a clinical trial to compare these two treatments. Material and methods We will include patients to be treated with aliskiren or enalapril (15 in each arm). Recruitment will take place in Swedish hospitals. Children 6 years or older with a glomerular filtration rate equal to or above 50 ml/min/1.73 m2 and adults equal to or above 30 ml/min/1.73 m2 will be included. Patients will be randomized for treatment with aliskiren or enalapril, as monotherapy or in combination with immune suppressive medications. After 6 months patients will switch to the other treatment and continue on the second treatment for an additional 2.5 years. Patients will be followed regularly regarding renal function, proteinuria, blood pressure, activation of the renin-angiotensin system and complement activation assays. After 1–3 years, when medically indicated or at the end of the study, a repeat renal biopsy will be performed to validate the effect of treatment on renal morphology and complement deposition. Conclusions The results of this study may provide more scientific evidence for, or against, the use of aliskiren in patients with C3 glomerulopathy.