Pediatrics Intern Seminar Childhood Nepbrotic Syndrome

1
Pediatrics Intern SeminarChildhood Nepbrotic
Syndrome

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

2
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
3
(No Transcript)
4
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
5
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 -

6
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
7
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)
8
Impression

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

9
DiscussionTreatments MethodsforChildhood
Idiopathic Nephrotic Syndrome
10
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

11
Pathophysiology
12
Yet to be identified
13
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

14
Pathogenesis Uncertain ?

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

15
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

16
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

17
Complications

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

18
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

19
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

20
Specific Tx

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

21
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

22
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

23
Specific Tx

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

24
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

25
Adverse Effects of Steroid

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

26
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

27
Cyclophosphamide
28
Side Effects of Cyclophosphamide
? Myelosuppression 32 ? Hemorrhagic cystitis
2.2 ? Bladder carcinoma ? Alopecia ? Gonadal
toxicity aspermia, amenorrhea Latta K, et al.,
Ped Nephrology, 2001
29
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

30
Cyclosporin
31
Cyclosporine
32
Specific Tx

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

33
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

34
(No Transcript)
35
MMF
36
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

37
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

38
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.

39
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.

40
Thank you !
41
(No Transcript)
42
Infections

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

43
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

44
Corticosteroid
Cyclosporine
MMF
Corticosteroid Cyclophosphamide
45
(No Transcript)
46
(No Transcript)
47
(No Transcript)
48
(No Transcript)
49
(No Transcript)
50
(No Transcript)
51
(No Transcript)
52
(No Transcript)
53
(No Transcript)
54
Dermatology Intern SeminarPityriasis Rubra
Pilaris

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

55
(No Transcript)
56
(No Transcript)
57
(No Transcript)
58
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.

59
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.

60

• Thank you !!!