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Nephrology Diseases & Chemotherapy

Nephrology Diseases & Chemotherapy. Idiopathic Nephrotic Syndrome (NS). Caused by renal diseases that increase the permeability across the glomerular filtration barrier. Characterized (first two are used diagnostically because the last two may not be seen in all patients) by:

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Nephrology Diseases & Chemotherapy

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  1. Nephrology Diseases & Chemotherapy

  2. Idiopathic Nephrotic Syndrome (NS) • Caused by renal diseases that increase the permeability across the glomerular filtration barrier. • Characterized (first two are used diagnostically because the last two may not be seen in all patients) by: 1. Nephrotic range proteinuria - Urine protein excretion >50 mg/kg per day 2. Hypoalbuminemia - Serum albumin <3 g/dL (30 g/L) 3. Edema 4. Hyperlipidemia

  3. Idiopathic Nephrotic Syndrome (NS) Two Common Types: 1. Steroid Resistant Minimal Residual Disease (MCD) with peak age between 2-3 years 2. Focal Segmental Glomerulosclerosis (FSGS) with peak age commonly seen at a later age.

  4. Pathophysiology • The exact pathogenesis remains unclear. • Possible theories postulated point to role of lymphokines and T cells • Immunosupressive therapies are used because of interlukine and T cell involvement. 1. Alkylating agents : Cyclophosphamide or Chlorambusil 2. Combination immunosuppression: Vincristine+cyclophosphamide+prednisone. 3. Cyclosporine 4. Cellcept or Prograf

  5. Membranous Nephropathy • It is a antibody mediated disease with unclear mechanism • Treatment strategies involve: 1. Chlorambucil + Prednisone 2. Cyclosporine + Prednisone 3. Cellcept+ Prednisone 4. Rituximab • Recent report indicate that patient treated with CD 20 had remission and reversal of pathological changes in the follow up biopsy.

  6. Systemic Vasculitis with Kidney Involvement Types of Vasculitis: 1. Polyarteritis Nodosa: Necrotizing inflammation of medium sized or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries or venules. 2. Kawasaki disease: Arteritis affecting large, medium and small arteries.

  7. Systemic Vasculitis with Kidney Involvement 3. Wegners’s Granulomatosis: Granulomatous inflammation involving respiratory tract and necrotizing vasculitis of the small to medium vessel. Glomerulonephritis is common. 4. Microscopic polyangitis: Necrotizing vasculitis affecting small vessel and causing glomerulonephritis

  8. Pathogenesis • Vasculitis is caused by the activation of inflammatory mediator systems in vessel walls. • Putative immunologic causes of vasculitis: 1. Immune complex Mediated 2. Antineutrophil cytoplasmic antibody mediated 3. Cell mediated

  9. Treatment • Treatment strategies are based on counteracting the immunogenic stimulus: 1. High dose solumedrol 2. Cyclophosphamide 3. Azathioprine 4. Plasmapheresis 5. Newer agents like Cellcept are being used for treatment of relapse, CD20 antibodies, severe disease and/or relapse

  10. Kidney Transplant • T8 cells are predominant T cells involved in kidney rejection. • Henceforth, protocols involve usage of: 1. Antithymocyte globulin 2. Monoclonal anti CD 25 antibodies 3. Prograf and 4. Cellcept. Although all these agents have different mode of action, they all mitigate the T cell proliferation or depletion.

  11. Kidney Transplant • Antibody mediated rejection is less commonly encountered but, carries a very high graft loss or dysfunction. • Treatment involves: 1. Plasmapheresis and 2. CD 20 antibodies (i.e.Rituximab)

  12. Small Vessel: Immune complex vasculitisHenochShonleinPurpura (HSP) One if the most common Vasculitides in Children Clinical Manifestations Palpable purpura: key to diagnosis; most common lower extremities and buttocks, color variation from red, purple, brown coloration Arthritis/arthralgia: 50-80%, usually large joints Glomerulonephritis: 1/3 of children have some level renal involvement Microscopic hematuria and mild proteinuria most common 10% have severe nephrotic syndrome GI involvement: 2/3 of children have some type of involvement Abdominal pain Gastrointestinal hemorrhage Cassidy, 2005

  13. HenochShonleinPurpura (HSP) Criteria for diagnosis : at least two of the following criteria Palpable purpura Less than 20 years old at onset Bowel angina Wall granulocytes on biopsy Treatment Supportive: hydration, nutrition, and pain control Occasionally short term steroid burst In presence of severe disease: steroids, cytotoxic medication Prognosis 2/3 resolve within 4 weeks 1/3 have re-occurrences between 6wks to 2 years on onset Cassidy, 2005

  14. Small Vessel: Immune complex vasculitisHenochShonleinPurpura (HSP)

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