Extracapillary Glomerulonephritis
Conditions
Keywords
Extracapillary glomerulonephritis, crescentic glomerulonephritis, rapidly progressive renal failure, chronic kidney disease, ACE-inhibitors, fibrosis
Brief summary
The natural course of extracapillary glomerulonephritis is severe leading to End-Stage Renal Disease (ESRD) or death in most cases. Despite immunosuppressive treatment, long-term renal outcome remains poor since active crescents usually progress to fibrotic scars with glomerular occlusion and disruption.In experimental models Angiotensin Converting Enzyme (ACE)-inhibitor therapy targeting the over-expression of angiotensin type 1 (AT1) receptors, that are responsible for dysregulated proliferation of parietal cell progenitors, blocks the formation of crescents and their fibrotic evolution. Should these drugs have similar effects in humans, ACE-inhibitor therapy on top of standard immunosuppression might be instrumental to prevent ESRD and promote renal function recovery in clinical practice.
Interventions
DRUGLisinopril
Sponsors
Istituto Di Ricerche Farmacologiche Mario Negri
Monia Lorini
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Rapidly progressive renal failure associated with acute nephritic syndrome and/or nephrotic syndrome; * Histology evidence of extracapillary proliferation with less than 50% of sclerotic glomeruli and associated with: 1. Type I: Anti-Glomerular Basement Membrane (GBM) antibody glomerulonephritis, 2. Type II: Pauci-immune vasculitis or Anti Neutrophil Cytoplasmic Antibody (ANCA) associated vasculitis; 3. Type III: Immune-complex mediated glomerular diseases: Proliferative lupus nephritis (LN), IgA nephropathy (IgAN)/ Schönlein-Henoch purpura, Type I membranoproliferative glomerulonephropathy (MPGN), Primary or secondary membranous nephropathy (MN), Primary or idiopathic immune complex glomerulonephritis. * Clinical indication to immunosuppressive therapy; * No specific indication to treatment with Renin Angiotensin System (RAS) inhibitors such as heart failure or coronary ischemic disease; * Written informed consent.
Exclusion criteria
* Pre-existing advanced chronic renal failure (creatinine clearance less than 20 ml/min/1.73m2); * Evidence of B or C virus active infection; * HIV infection; * Recent diagnosis of malignancy; * Prolonged bleeding time and any other contraindication to kidney biopsy evaluation; * Any specific contraindication to ACE inhibitor therapy (that is: history of angioedema or other treatment-related serious adverse events); * Pregnancy or lactating; * Women of childbearing potential without following a scientifically accepted form of contraception; * Inability to understand the risks and benefit of the study or evidence of an uncooperative attitude; * Legal incapacity.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The extent of extracapillary proliferation on light microscopy, measured as % of total glomeruli with proliferative lesions at post-treatment repeat biopsy. | Changes from baseline and 6 and 18 month. |
Secondary
| Measure | Time frame |
|---|---|
| Expression of parietal cell proliferation markers at glomerular level, graded on a scale of 0 to 3 (0: no staining, 1: mild, 2: moderate, 3: strong diffuse | Changes from baseline and 6 and 18 month. |
| Number of fibrosclerotic crescents | Changes from baseline and 6 and 18 month. |
| Glomerular Filtration Rate (GFR) measured by iohexol plasma clearance | Changes from baseline and 6, 12 and 18 month. |
Countries
Italy
Contacts
Primary ContactBarbara Ruggiero, MD
Backup ContactEttore Sabadini, MD
Outcome results
None listed