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Pediatrics Intern Seminar Childhood Nepbrotic Syndrome Supervisors: 邱元佑 醫師 周信旭 醫師 Intern: 黃鈺堯.

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Presentation on theme: "Pediatrics Intern Seminar Childhood Nepbrotic Syndrome Supervisors: 邱元佑 醫師 周信旭 醫師 Intern: 黃鈺堯."— Presentation transcript:

1 Pediatrics Intern Seminar Childhood Nepbrotic Syndrome Supervisors: 邱元佑 醫師 周信旭 醫師 Intern: 黃鈺堯

2 Patient Information ● 黃啟展 ● 5 y/o male ● 5 y/o male ● G3P3NO, NSD, Full term ● BW: 21.1 kg (25~50%)Ht: cm (75~90%) CC: Generalized edema for 2+ weeks

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4 Brief History 92/12/08 Periorbital edema noted Generalized edema: face, limbs, scrotum, abdominal distension, oligouria W’t gain 20 kg → 22 kg (in days) 92/12/17 新樓 Hospital admission U/A: protein (+++), Alb: 1.7, cholesterol: 455 Impression: nephrotic syndrome Prednisolone + Albumin + Lasix CXR: R’t pleural effusion s/p thoracentesis 92/12/22 Transferred to 成醫 Ped ward by family’s request

5 ● SG: ● BIL: - ● pH: 8.0 ● ERY: 10 ● LEU: 15 ● WBC: ● NIT: - ● RBC: ● PRO: > 300 ● Epith: ● Glu: - ● Cast: - ● KET: - ● Crystal: - ● UBG: normal ● Bacteria: - Urine Analysis

6 Lab Results PltNaKPCaCl 652k↑ WBCSegLymphMonoBandCRP 13900↑80↑14↓6-< 7.0 RBCHbBUNCrGOTGPT ↓2818

7 Lab Results AlbuminT proteinTGCholesterol ↓606↑433↑ C3C4ASLOIgGHbsAg < ↓- ● CCr = 60.7 ml/min ● DPL = 11.9 g/24hrs ● Protein selective index = < 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 Discussion Treatments Methods for Childhood Idiopathic Nephrotic Syndrome

10 ● Proteinuria > 40 mg/m 2 /hr (> 1 g/m 2 /24hrs) ● Hypoproteinemia Total protein < 5.5 g/dL; Alb < 2.5 g/dL ● Hyperlipidemia Cholesterol > 250 mg/dL ● Edema Periorbital, lower limbs, scrotum, generalized, pitting Clinical Characteristics

11 Pathophysiology

12 Yet to be identified

13 ● 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 > 150 kd restricted Loss of size-selectivity → MN Pathophysiology

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

15 ● Incidence: 2 ~ 3 per children ● Idiopathic nephrotic syndrome 90% Primary Nephritis (-) Primary extrarenal disease (-) Onset: 2 ~ 7 y/o Male: female (2:1) Three common histologies Epidemiology

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

17 ● Infection: Spontaneous peritonitis 2~ 6% ● Thromboembolic diseases: risk of renal vein thrombosis Complications

18 ● 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 Treatment Goals

19 Severe edema: Pleural effusion, ascites, scrotal edema ● Restricted water / salt (< 2 g/day) ● 25% Albumin ivd (1 g/kg/day) ● Furosemide (1 ~ 2 mg/kg/4hrs) ● Monitor vol. depletion, e - disturbance, renal function Non - Specific Tx

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

21 ● 1 ~ 8 y/o: steroid-responsive MCNS 87% Try steroid therapy, hold renal biopsy ● Prednisolone (2 mg/kg/day; 60 mg/m 2 /day) po divided dose ● Proteinuria (1+ or less) for 4 consecutive days → “steroid-responsive” ● 75% MCNS remission by 2 wks ● Prednisolone (60 mg/m 2 /day) qod for 4 wks Oral Corticosteroid

22 ● 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: > 2 relapses in 6 months of initial response or > 4 relapses in any 12 months > 60% relapse in steroid-responsive cases Response to Steroid

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

24 ● 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 13.1±12.5 wks Kirpekar R, et al., Am J of Kidney Disease, 2002 Pulse Methylprednisolone

25 ● Buffalo hump / moon face ● Cutaneous striae ● Osteoporosis ● Hypertension ● Hyperglycemia ● Dyslipidemia ● Muscle weakness / fatigability ● Infection Adverse Effects of Steroid

26 ● 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 p’ts Eddy A, et al., The Lancet, 2003 Cyclophosphamide (Endoxan)

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 ● Immunosuppressant for transplantation ● Calcineurin inhibitor: ↓IL-2,IL-3,IL-4, GM-CSF, TNF-α → ↓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 Cyclosporin (Sandimmun)

30 Cyclosporin

31 Cyclosporine

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

33 ● Prevents allograft rejection ● Suppress de novo purine synthesis: ↓T cell / B cell / smooth muscle cell / fibroblast proliferation ● 0.8 ~ 1.2 g/m 2 /day ● Leukopenia, GI discomfort, diarrhea, malaise, splenomegaly Barletta G, et al., Ped Nephrology, 2003 Mycophenolate Mofetil (CellCept)

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35 MMF

36 ● 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 Levamisole

37 ● 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 Conclusion

38 References ● Nelson 17th edition ● Eddy A., et al. Nephrotic syndrome in childhood. The Lancet. 362:629-39, ● Habashy D., et al. Interventions for steroid-resistant NS. Ped Nephrology. 18: , ● Schwarz A. New aspects of treatment of NS. J Am Soc Nephrol. 12: S44-47, ● Orth S., et al. The Nephrotic syndrome. NEJM. 338(17): , ● Ponticelli C, et al. Other immunosuppressive agents for FSGS. Seminars in Nephrol. 23(2): , ● Tenbrock K., et al. Levamisole treatment in steroid sensitive and steroid resistant NS. Ped Nephrology. 12: , 1998.

39 References ● Day C., et al. MMF in the treatment of resistant idiopathic NS. Nephrol Dial Transplant. 17: , ● Barletta G., et al. Use of MMF in steroid dependant and resistant NS. Ped Nephrology. 18: , ● Yorgin.P. Pulse methylprednisolone Tx of idiopathic steroid resistant NS. Ped Nephrology. 16:245-50, ● Kirpekar R., et al. Clinicopathgologic correlates predict... Am J of Kidney Diseases. 39(6): , 2001.

40 Thank you !

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42 ● Spontaneous peritonitis 2~ 6% Sepsis, pneumonia, cellulitis, UTI Streptococcus pneumoniae, GNB common ● Protein deficiency, ↓immunoglobulin, ↓complement, ascites, immunosuppressive therapy Infections

43 ● 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 Thromboembolic diseases

44 Corticosteroid Cyclosporine Corticosteroid Cyclophosphamide MMF

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54 Dermatology Intern Seminar Pityriasis Rubra Pilaris Intern: 黃鈺堯 Supervisor: 陳冠宇 醫師 許漢銘 醫師

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58 References ● Coupland S. E., et al. Ocular Adnexal Lymphoma: Five... Survey of Ophthalmology. 47(5): , 2002 Sept- Oct. ● Shields C. L., et al. Conjunctival Lymphoid Tumors: Clinical... Ophthalmology. 108(5): , ● Coupland S. E., et al. Lymphoproliferative Lesions of the Ocular Adnexa. Ophthalmology. 105: , ● Zhongxing Liao, et al. Mucosa-Associated Lymphoid Tissue Lymphoma With Initial Supradiaphragmatic Presentation: Natural... Int. J. Radiation Oncology Biol. Phys. 48(2): , ● Blasi M. A., et al. Local Chemotherapy with Interferon-a for Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma. Ophthalmology. 108: , 2001.

59 References ● Lee D. H., et al. Bilateral Conjunctival Mucosa- Associated Lymphoid Tissue Lymphoma Misdiagnosed as Allergic Conjunctivitis. Cornea. 20(4): , ● Akpek E. K., et al. Conjunctival Lymphoma Masquerading as Chronic Conjunctivitis. Ophthalmology. 106: , ● Sharara N., et al. Ocular Adnexal Lymphoid Proliferations: Clinical... Ophthalmology. 110: , 2003.

60 Thank you !!!


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