ACE-inhibitors in Extracapillary Glomerulonephritis

A Pilot, Prospective, Randomized, Open-label, Blinded Endpoint (Probe) Histopathology Trial to Assess the Effects of ACE- Inhibition Therapy on Glomerular Proliferative Lesions in Patients With Extracapillary Glomerulonephritis

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.

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.