The aim of this cross-over trial is to assess aliskiren, a direct renin inhibitor, as a novel treatment to block complement activation in the kidneys and thereby attenuate renal disease and stabilize or improve kidney function and compare it to the currently used treatment with the angiotensin converting enzyme inhibitor, enalapril, in patients with the complement-mediated renal disease C3 glomerulopathy. Patients will be randomized to one or the other treatment for the first 6 months and then switch to the other treament for the following 2.5 years. Treatment will continue for altogether 3 years for each patient.
Children ≥ 6 years and adults.
Initial diagnosis of Dense Deposit Disease and C3 glomerulonephritis confirmed by kidney biopsy obtained not more than 2 years before the first dose of the study drug.
Either absence of treatment at the study start or ongoing treatment with aliskiren, angiotensin converting enzyme inhibitors, angiotensin receptor blockers or immune suppressive medications (such as mycophenolate mofetil/MMF or corticosteroids)
the patient's legal guardians if the patient is less than 15 years old
Known allergy to aliskiren, ACEi or substances contained in these preparations.
Angioedema caused by aliskiren or enalapril
Weight < 25 kg
Glomerular filtration rate ≤ 50 ml/min/1.73 m2 (measured by iohexol clearance) in children and ≤ 30 ml/min/1.73 m2 in adults.
Crossover
Aliskiren
DrugPatients will be randomized to start treatment with aliskiren tablet 150 mg every other day up to 300 mg daily depending on weight. After 6 months switch to enalapril 2.5-20 mg daily and continue with that 2.5 years.
Enalapril
DrugPatients will be randomized to start with enalapril 2.5-20 mg daily depending on weight. After 6 months switch to aliskiren tablet 150 mg every other day up to 300 mg daily depending on weight and continue with this treatment for 2.5 years.
C3 levels in serum
To assess the effect and safety of aliskiren as compared to enalapril on reducing systemic complement activation as assayed by C3 levels in serum.
Complement deposition in kidneys
To quantify complement deposition in kidney biopsies from patients with C3 glomerulopathy using immunohistological staining
C3a in serum
To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on C3a in serum
C3dg in plasma
To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on C3dg in plasma
C5a in serum
To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on C5a in serum
Glomerular basement membrane thickness
To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on glomerular basement membrane thickness assessed by electron microscopy measurement
Renal function
To assess the effect of aliskiren compared to currently used treatment with the ACEi enalapril on kidney function measured as iohexol clearance glomerular filtration rate
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