Hydroxychloroquine Sulfate for Reduction of Proteinuria in Patients With IgA Nephropathy: a Self- Controlled Study
Condition: Primary IgA Nephropathy
MeSH terms: Kidney Diseases; Glomerulonephritis, IGA
Study type: Interventional
Phase: Phase 4

Summary: 
      IgA nephropathy is the most common type of primary glomerulonephritis and might caused by
      deposition of immune complex containing IgA in mesangium and causing local immune activation.
      Hydroxychloroquine reduces the activation of dendritic cells and the inflammatory process and
      showed the potential effect of treatment of patients with IgA nephropathy.

      The investigators study will recruite IgA nephropathy patients with proteinuria range from
      0.75 to 3.5g/d even after three-month treatment by sufficient ACEi/ARB. The patients were
      treated with Hydroxychloroquine 300-400mg/d according to eGFR. The proteinuria will recorded
      every two months and total four months. Then, the drug will be stopped for two months for
      observation of change of proteinuria.
    

Detailed description: 
      Immunoglobulin A (IgA) nephropathy is the most common type of primary glomerulonephritis
      worldwide. Several studies indicated that 6-43% of IgA nephropathy patients would develop
      end-stage kidney disease (ESKD) over a period of 10 years. The clinical risk factors for
      progression are hypertension, protienuria, impaired renal function and histologic lesions at
      presentation. There is no well accepted optimal therapy for patients with IgA. Current
      established therapies include full RAS inhibition and optimal blood pressure control for
      patients with proteinuria and/or hypertension.

      Hydroxychloroquine has been used for many years to treat malaria. It is also used to treat
      systemic lupus erythematosus, rheumatic disorders like rheumatoid arthritis and Sjögren's
      Syndrome. Recently, several studies found that Hydroxychloroquine could reduce the risk of
      ESRD in patients with lupus nephrits. The mechanism of the treatment wasn't well known so
      far. Some investigators found that Hydroxychloroquine increases lysosomal pH in antigen
      presenting cells. In inflammatory conditions, it blocks toll-like receptors on plasmacytoid
      dendritic cells (PDCs). Toll-like receptor 9 (TLR 9), which recognizes DNA-containing immune
      complexes, leads to the production of interferon and causes the dendritic cells to mature and
      present antigen to T cells. Hydroxychloroquine, by decreasing TLR signaling, reduces the
      activation of dendritic cells and the inflammatory process.

      The pathogenesis of IgA nephropathy included the deposition of immune complex containing IgA
      in mesangium and causing local immune activation and injury to kidney. Therefore,
      Hydroxychloroquine might have the potential effect of anti-inflammation in patients with IgA
      nephropathy, reduced the proteinuria and had the renal protect effect.

      Our study will recruite IgA nephropathy patients with proteinuria range from 0.75 to 3.5g/d
      even after three-month treatment by sufficient ACEi/ARB. The patients were treated with
      Hydroxychloroquine 300-400mg/d according to eGFR. The proteinuria will recorded every two
      months and total four months. Then, the drug will be stopped for two months for observation
      of change of proteinuria.
    

Intervention name(s): Hydroxychloroquine Sulfate
Intervention type(s): Drug
Intervention description(s): Hydroxychloroquine Sulfate: 0.1 Tid(eGFR 30-59);0.2 Bid (eGFR>60)
Intervention MeSH terms: Hydroxychloroquine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment