ACE-inhibitors in Extracapillary Glomerulonephritis

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Monia Lorini
• Collaborator: Istituto Di Ricerche Farmacologiche Mario Negri
• Treatments: Angiotensin-Converting Enzyme Inhibitors; Lisinopril

Criteria

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.