Nephrology Diseases Nephrology Diseases & Chemotherapy& Chemotherapy

Idiopathic Nephrotic Idiopathic Nephrotic Syndrome (NS)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

Idiopathic Nephrotic Idiopathic Nephrotic Syndrome (NS)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.

PathophysiologyPathophysiologyThe exact pathogenesis remains unclear.Possible theories postulated point to role

of lymphokines and T cellsImmunosupressive therapies are used

because of interlukine and T cell involvement.1. Alkylating agents : Cyclophosphamide or Chlorambusil2. Combination immunosuppression:

Vincristine+cyclophosphamide+prednisone.3. Cyclosporine4. Cellcept or Prograf

Membranous Membranous NephropathyNephropathyIt is a antibody mediated disease

with unclear mechanism Treatment strategies involve:

1. Chlorambucil + Prednisone2. Cyclosporine + Prednisone3. Cellcept+ Prednisone4. Rituximab

Recent report indicate that patient treated with CD 20 had remission and reversal of pathological changes in the follow up biopsy.

Systemic Vasculitis Systemic Vasculitis with Kidney with Kidney InvolvementInvolvementTypes 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.

Systemic Vasculitis Systemic Vasculitis with Kidney with Kidney InvolvementInvolvement3. 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

PathogenesisPathogenesisVasculitis is caused by the

activation of inflammatory mediator systems in vessel walls.

Putative immunologic causes of vasculitis:1. Immune complex Mediated2. Antineutrophil cytoplasmic antibody mediated3. Cell mediated

TreatmentTreatmentTreatment strategies are based on

counteracting the immunogenic stimulus:

1. High dose solumedrol2. Cyclophosphamide3. Azathioprine4. Plasmapheresis5. Newer agents like Cellcept

are being used for treatment of relapse, CD20 antibodies, severe disease and/or relapse

Kidney TransplantKidney TransplantT8 cells are predominant T cells

involved in kidney rejection.Henceforth, protocols involve usage of:

1. Antithymocyte globulin2. 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.

Kidney TransplantKidney TransplantAntibody 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)

Small Vessel: Immune complex Small Vessel: Immune complex vasculitis vasculitis Henoch Shonlein Purpura (HSP)Henoch Shonlein Purpura (HSP)

One if the most common Vasculitides in ChildrenClinical 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

Henoch Shonlein Purpura Henoch Shonlein Purpura (HSP)(HSP)• Criteria for diagnosis : at least two of the Criteria for diagnosis : at least two of the

following criteriafollowing criteria– Palpable purpuraPalpable purpura– Less than 20 years old at onsetLess than 20 years old at onset– Bowel anginaBowel angina– Wall granulocytes on biopsyWall granulocytes on biopsy

• TreatmentTreatment– Supportive: hydration, nutrition, and pain control Supportive: hydration, nutrition, and pain control – Occasionally short term steroid burstOccasionally short term steroid burst– In presence of severe disease: steroids, cytotoxic In presence of severe disease: steroids, cytotoxic

medicationmedication• PrognosisPrognosis– 2/3 resolve within 4 weeks2/3 resolve within 4 weeks– 1/3 have re-occurrences between 6wks to 2 years on 1/3 have re-occurrences between 6wks to 2 years on

onsetonsetCassidy, 2005

Small Vessel: Immune complex Small Vessel: Immune complex vasculitis vasculitis

Henoch Shonlein Purpura (HSP)Henoch Shonlein Purpura (HSP)