Pediatrics Intern Seminar Childhood Nepbrotic Syndrome - PowerPoint PPT Presentation

Title: Pediatrics Intern Seminar Childhood Nepbrotic Syndrome


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Pediatrics Intern SeminarChildhood Nepbrotic
Syndrome

• Supervisors ??? ??
• ??? ??
• Intern ???

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Patient Information

• ? ??? ? 5 y/o male
• ? 5 y/o male ? G3P3NO, NSD, Full term
• ? BW 21.1 kg (2550) Ht 109.2 cm (7590)

CC Generalized edema for 2 weeks
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Brief History
92/12/08
Periorbital edema noted Generalized edema face,
limbs, scrotum, abdominal distension,
oligouria Wt gain 20 kg ? 22 kg (in days)
?? Hospital admission U/A protein (), Alb
1.7, cholesterol 455 Impression nephrotic
syndrome Prednisolone Albumin Lasix CXR
Rt pleural effusion s/p thoracentesis
92/12/17
92/12/22
Transferred to ?? Ped ward by familys request
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Urine Analysis

• ? SG 1.015 ? BIL -
• ? pH 8.0 ? ERY 10
• ? LEU 15 ? WBC 1 - 3
• ? NIT - ? RBC 1 - 2
• ? PRO gt 300 ? Epith 0 - 1
• ? Glu - ? Cast -
• ? KET - ? Crystal -
• ? UBG normal ? Bacteria -

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Lab Results
WBC Seg Lymph Mono Band CRP
13900? 80? 14? 6 - lt 7.0
RBC Hb BUN Cr GOT GPT
5.27 14.1 19 0.5? 28 18
Plt Na K P Ca Cl
652k? 139 4.5 3.9 8.6 107
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Lab Results
Albumin T protein TG Cholesterol
3.0 5.6? 606? 433?
C3 C4 ASLO IgG HbsAg
102 19.6 lt 25.0 143? -
? CCr 60.7 ml/min ? DPL 11.9 g/24hrs ?
Protein selective index 0.056 lt 0.1 (selevtive)
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Impression

• Neprotic syndrome, r/o steroid-resistance
• ? Prednisolone 2 mg/kg/day since 12/17
• ? Albumin infusion x 6 courses

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DiscussionTreatments MethodsforChildhood
Idiopathic Nephrotic Syndrome
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Clinical Characteristics

• ? Proteinuria gt 40 mg/m2/hr (gt 1 g/m2/24hrs)
• ? Hypoproteinemia Total protein lt 5.5 g/dL Alb lt
  2.5 g/dL
• ? Hyperlipidemia Cholesterol gt 250 mg/dL
• ? Edema Periorbital, lower limbs, scrotum,
  generalized, pitting

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Pathophysiology
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Yet to be identified
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Pathophysiology

• ? Charge-selective barrier
• Sialoprotein (-) / polyanionic
  glycosaminoglycans
• 69 150 kd restricted (i.e. Albumin)
• Loss of charge-selectivity ? MCNS
• ? Size-selective barrier
• Pore size in GMB
• gt 150 kd restricted
• Loss of size-selectivity ? MN

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Pathogenesis Uncertain ?

• Altered T-lymphocyte response
• ?
• Plasma factor ?
• ?
• Podocyte protein expression / function
• ?
• Glomerular capillary wall permeability
• Eddy A, et al., The Lancet, 2003

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Epidemiology

• ? Incidence 2 3 per 100000 children
• ? Idiopathic nephrotic syndrome 90
• Primary
• Nephritis (-)
• Primary extrarenal disease (-)
• Onset 2 7 y/o
• Male female (21)
• Three common histologies

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Histopathology

• 1. Minimal change nephroytic syndrome 85
• Effacement of podocyte foot process
• 95 steroid-responsive
• 2. Focal segmental glomerulosclerosis 10
• Juxtamedullary segmental scarring
• lt 20 steroid-responsive
• Progressive, ESRD in 2 5 yrs
• 3. Membranous nephropathy 5
• Increased mesangial cells / matrix
• 50 steroid-responsive

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Complications

• ? Infection Spontaneous peritonitis 2 6
• ? Thromboembolic diseases risk of renal vein
  thrombosis

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Treatment Goals

• ? Non-specific relieve S/S and secondary effects
  
• ? Specific immunosuppressive therapy aimed at
  modulating the immune component of the disease
• ? Minimize complications and those of
  immunosuppressive drugs

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Non - Specific Tx

• Severe edema
• Pleural effusion, ascites, scrotal edema
• ? Restricted water / salt (lt 2 g/day)
• ? 25 Albumin ivd (1 g/kg/day)
• ? Furosemide (1 2 mg/kg/4hrs)
• ? Monitor vol. depletion, e- disturbance, renal
  function

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Specific Tx

• 1. First-line
• Oral corticosteroid
• 2. Second-line
• Pulse methylpredisolone, Cyclophosphamide,
  Cyclosporin
• 3. Other immunosuppressive agents
• Levamisole, Mycophenolate mofetil

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Oral Corticosteroid

• ? 1 8 y/o steroid-responsive MCNS 87
• Try steroid therapy, hold renal biopsy
• ? Prednisolone (2 mg/kg/day 60 mg/m2/day) po
  divided dose
• ? Proteinuria (1 or less) for 4 consecutive days
  ? steroid-responsive
• ? 75 MCNS remission by 2 wks
• ? Prednisolone (60 mg/m2/day) qod for 4 wks

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Response to Steroid

• ? Steroid-resistant
• Proteinuria (2 or more) after 1 month of daily
  Prednisolone use
• Renal biopsy indicated
• ? Steroid-dependent
• Relapse (proteinuria edema) after switching to
  or terminating qod Prednisolone Tx
• ? Frequently relapsing
• gt 2 relapses in 6 months of initial response or
  gt 4 relapses in any 12 months
• gt 60 relapse in steroid-responsive cases

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Specific Tx

• 1. First-line
• Oral corticosteroid
• 2. Second-line
• Pulse methylpredisolone, Cyclophosphamide,
  Cyclosporin
• 3. Other immunosuppressive agents
• Levamisole, Mycophenolate mofetil

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Pulse Methylprednisolone

• ? 10 30 mg/kg bolus (Max 1000 mg) iv qod x 6
  doses
• Weekly pulse x 4 wks
• Every-other-week pulse x 4 doses
• ? Combination with oral corticosteroids,
  cyclophosphamide, or cyclosporin
• ? Remission rate 64 (27/42) in
  steroid-resistant NS by 13.112.5 wks
• Kirpekar R, et al., Am J of Kidney Disease,
  2002

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Adverse Effects of Steroid

• ? Buffalo hump / moon face
• ? Cutaneous striae
• ? Osteoporosis
• ? Hypertension
• ? Hyperglycemia
• ? Dyslipidemia
• ? Muscle weakness / fatigability
• ? Infection

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Cyclophosphamide (Endoxan)

• ? Alkylating agent used in C/T
• ? Interferes DNA cross-link covalently
• ? For steroid-resistant / dependent / frequently
  relapsing NS
• ? 2 2.5 mg/kg/day for 8 12 wks
• ? Combined Prednisolone qod Tx
• ? Remission 25 30 steroid-unresponsive pts
• Eddy A, et al., The Lancet, 2003

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Cyclophosphamide
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Side Effects of Cyclophosphamide
? Myelosuppression 32 ? Hemorrhagic cystitis
2.2 ? Bladder carcinoma ? Alopecia ? Gonadal
toxicity aspermia, amenorrhea Latta K, et al.,
Ped Nephrology, 2001
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Cyclosporin (Sandimmun)

• ? Immunosuppressant for transplantation
• ? Calcineurin inhibitor ?IL-2,IL-3,IL-4, GM-CSF,
  TNF-a ? ?T cell proliferation
• ? 5 6 mg/kg/day oral Prednisolone use
• ? Remission rate 85 for steroid-responsive NS
• ? Side effects gingival-hyperplasia, hirsutism,
  risk of cyclosporin-induced vasculopathy
• ? High nephrotoxicity monitor renal function
• Eddy A, et al., The Lancet, 2003

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Cyclosporin
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Cyclosporine
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Specific Tx

• 1. First-line
• Oral corticosteroid
• 2. Second-line
• Pulse methylpredisolone, Cyclophosphamide,
  Cyclosporin
• 3. Other immunosuppressive agents
• Levamisole, Mycophenolate mofetil

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Mycophenolate Mofetil(CellCept)

• ? Prevents allograft rejection
• ? Suppress de novo purine synthesis
• ?T cell / B cell / smooth muscle cell /
  fibroblast proliferation
• ? 0.8 1.2 g/m2/day
• ? Leukopenia, GI discomfort, diarrhea, malaise,
  splenomegaly
• Barletta G, et al., Ped Nephrology, 2003

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MMF
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Levamisole

• ? Antihelmintic drug
• ? Immunomodulatory effect ?
• ? 2.5 mg/kg qod, median 10 months
• ? ?relapse in frequently relapsing NS
• ? Risks of leukopenia, hepatoxity,
  agranulocytosis, vasculitis, encephalopathy
• Tenbrock K, et al., Ped Nephrology, 1998

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Conclusion

• ? Steroid-responsiveness most important
  prognostic factor
• ? Oral Prednisolone first-line drug
• ? Alkylating agents, immuno uppressants for
  steroid-resistant/dependant, frequently relapsing
  nephrotic syndrome
• ? Levamisole, MMF require larger trials for
  efficacy

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References

• ? Nelson 17th edition
• ? Eddy A., et al. Nephrotic syndrome in
  childhood. The Lancet. 362629-39, 2003.
• ? Habashy D., et al. Interventions for
  steroid-resistant NS. Ped Nephrology. 18906-912,
  2003.
• ? Schwarz A. New aspects of treatment of NS. J
  Am Soc Nephrol. 12 S44-47, 2001.
• ? Orth S., et al. The Nephrotic syndrome. NEJM.
  338(17)1202-1211, 1998.
• ? Ponticelli C, et al. Other immunosuppressive
  agents for FSGS. Seminars in Nephrol. 23(2)
  242-48, 2003.
• ? Tenbrock K., et al. Levamisole treatment in
  steroid sensitive and steroid resistant NS. Ped
  Nephrology. 12459-462, 1998.

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References

• ? Day C., et al. MMF in the treatment of
  resistant idiopathic NS. Nephrol Dial Transplant.
  172011-13, 2002.
• ? Barletta G., et al. Use of MMF in steroid
  dependant and resistant NS. Ped Nephrology.
  18833-837, 2003.
• ? Yorgin.P. Pulse methylprednisolone Tx of
  idiopathic steroid resistant NS. Ped Nephrology.
  16245-50, 2001.
• ? Kirpekar R., et al. Clinicopathgologic
  correlates predict... Am J of Kidney Diseases.
  39(6)1143-1152, 2001.

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Infections

• ? Spontaneous peritonitis 2 6
• Sepsis, pneumonia, cellulitis, UTI
• Streptococcus pneumoniae, GNB common
• ? Protein deficiency, ?immunoglobulin,
  ?complement, ascites, immunosuppressive therapy

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Thromboembolic diseases

• ? Risk of renal vein thrombosis, pulmonary
  emboli, deep vein thrombosis
• ? Urine loss of antithrombin III
• Fibrinogen clotting factors synthesis
• Platelet abnormalty thrombocytosis,
  ?aggregability
• Hyperviscosity
• Hyperlipidemia

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Corticosteroid
Cyclosporine
MMF
Corticosteroid Cyclophosphamide
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Dermatology Intern SeminarPityriasis Rubra
Pilaris

• Intern ???
• Supervisor ??? ??
• ??? ??

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References

• ? Coupland S. E., et al. Ocular Adnexal Lymphoma
  Five... Survey of Ophthalmology. 47(5)470-490,
  2002 Sept-Oct.
• ? Shields C. L., et al. Conjunctival Lymphoid
  Tumors Clinical... Ophthalmology.
  108(5)979-984, 2001.
• ? Coupland S. E., et al. Lymphoproliferative
  Lesions of the Ocular Adnexa. Ophthalmology.
  1051430-1441, 1998.
• ? Zhongxing Liao, et al. Mucosa-Associated
  Lymphoid Tissue Lymphoma With Initial
  Supradiaphragmatic Presentation Natural... Int.
  J. Radiation Oncology Biol. Phys. 48(2)399-403,
  2000.
• ? Blasi M. A., et al. Local Chemotherapy with
  Interferon-a for Conjunctival Mucosa-Associated
  Lymphoid Tissue Lymphoma. Ophthalmology.
  108559-562, 2001.

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References

• ? Lee D. H., et al. Bilateral Conjunctival
  Mucosa-Associated Lymphoid Tissue Lymphoma
  Misdiagnosed as Allergic Conjunctivitis. Cornea.
  20(4)427-429, 2001.
• ? Akpek E. K., et al. Conjunctival Lymphoma
  Masquerading as Chronic Conjunctivitis.
  Ophthalmology. 106757-760, 1999.
• ? Sharara N., et al. Ocular Adnexal Lymphoid
  Proliferations Clinical... Ophthalmology.
  1101245-1254, 2003.

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• Thank you !!!