Steroid resistant Minimal change disease : Focal segmental

Nephrology Diseases &
Idiopathic Nephrotic
Syndrome (NS)
Caused by renal diseases that increase the
permeability across the glomerular filtration
 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
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.
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
2. Combination immunosuppression:
3. Cyclosporine
4. Cellcept or Prograf
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.
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
2. Kawasaki disease: Arteritis affecting
large, medium and small arteries.
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
Vasculitis is caused by the activation of
inflammatory mediator systems in vessel
 Putative immunologic causes of vasculitis:
1. Immune complex Mediated
2. Antineutrophil cytoplasmic antibody
3. Cell mediated
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
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.
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)
Small Vessel: Immune complex vasculitis
Henoch Shonlein Purpura (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
 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 (HSP)
Criteria for diagnosis : at least two of the following
Palpable purpura
Less than 20 years old at onset
Bowel angina
Wall granulocytes on biopsy
– Supportive: hydration, nutrition, and pain control
– Occasionally short term steroid burst
– In presence of severe disease: steroids, cytotoxic medication
– 2/3 resolve within 4 weeks
– 1/3 have re-occurrences between 6wks to 2 years on onset
Cassidy, 2005
Small Vessel: Immune complex vasculitis
Henoch Shonlein Purpura (HSP)