Minimal Change Disease R1 조윤호

Introduction Major Cause of Nephrotic syndrome(NS) Minimal change disease(MCD) Focal segmental glomerulosclerosis(FSGS) - Podocytopathies - Primary lesion of podocyte or Glomerular epitherlial cell

MCD vs FSGS Same By Different By (in some) Diffuse foot process fusion No Immune deposit, Severe functional defect, Glomerular permselectivity Glucocorticoid Tx. Responsive (MCD>FSGS) Different By (in some) Pathogenically MCD – Glomerular permeability factor FSGS – Eleveated Soluble urokinase response

Pathology Glomeruli appear normal, Foot process withdrow, No complement or immunoglobulin deposits, Glomerular size normal Diffuse fusion of Epithelial foot processes Degree of fusion – Not correlated with Proteinuria

Pathology - Genesis Glomerular permeablility factor T cell dysfunction – 세포성 면역이 주요병발 원인이라 가정 Measles infection lead to Remission Hodgkin lymphoma 호발, Atopic individual 호발 Glucocorticoid & Cyclophosphamide (Modify cell immune) 동물실험에서 CD34 발현하는 미완성 T cell 이 MCD에서 확인됨. B cell dysfunction MCD에서 Rituximab 효과 있음 Glomerular permeability factor – B cell or T cell에서 발현

Pathology - Genesis Glomerular permeability factor T cell hybridoma 투여시 쥐에서 MCD 발생 Hodgkin lymphoma 환자에서 MCD 호발, Prednisone과 Cyclosporine 비효과적, Rituximab ChemoTx. 효과적 사람에게 확인 안됨, 동물실험에서 IL-13가 Albuminuria 유발 Role of Glomerular Basement Membrane 추정적 가설, Capillary wall은 완벽하게 이해 안됨 Glomerular capillary wall – Fenestrated endothelium, Glomerular basement membrane(GBM), Slit diaphragm(podocyte사이) Endothelium and GBM – Strongly anionic -> Albumin 밀어냄 Glomerular permiablity factor가 Anionicity 줄임 -> Albuminuria Genetic disease – NPHS2 연관

Etiology Drug, Neoplasm, Infection, Allergy Drugs Neoplasm Infection NASIDs, Selective COX-2 inhibitors Ampicillin, Rifampicin, cephalosporins, Lithium D-penicillamine, Tiopronin, Pamidronate and Bisphosphate, Sulfasalazine Neoplasm Hematologic Malig. - Hodgkin lymphoma, Non-HL, Leukemia MCD 후 Hodgkin lymphoma 병발 Solid tumor 에서 rare Infection Rare but Syphilis, TB, Mycoplasma, HCV, HIV Allergy MCD 30%는 allergy 병력 있음

Clinical manifestations AGE Under 10 – Nephrotic syndrome 90%는 MCD 있음 Over 10 – Nephrotic syndrome 50%는 MCD 있음 Adult - Nephrotic syndome 10-15% Ethnicity Highest on Asian and Caucasian Presenstation Sudden onset a week or two, After URI Proteinuria, Mostly albuminuria – 3.5~4g/day 이상 Weight gain ,Edema, Hypoalbuminemia(1.5-2g/dl), Hyperlipidemia Sudden onset Children sudden onset – Bx. 불필요 Adult sudden onset – MCD 의심 가능 but Bx. 필요

Clinical manifestations Adult vs Children Micro Hematuria – Adult(common) > Children Serum creatinine – Modestly 30-40% Adult MCD Age 45, SCr 1.4mg/dl, eGFR 72ml/min, Proteinuria 9.9g/day, Hematuria 29%, SAlb 2.2g/dl, HTN 43%, ARF 18% Complication Thromboembolism, Encapsulated org infection Risk

Diagnosis Children Adult DDX from other NS MCD vs FSGS Presumptive diagnosis Short glococorticoid Tx. 효과적 2개월 이상 Full dose steroid Tx. 효과 없을시 SR-NS로 정의 Adult 다른 Glomerular disease와 구분 어려움, short steroid Tx. 비효과적 8주 내에 관해 오기도 하나 16주 이상 치료 필요하기도 함. DDX from other NS Light Micro – Norm glomeruli, No complement& immune deposit Electron Micro – Epithelial foot processes diffuse fusion MCD vs FSGS FSGS – Segmental Glomerulosclerosis least one

Diagnosis MCD on Elder Histologic DDx. Difficult – Glomeruli 쇄퇴, Vascular lesion, interstitial fibrosis Aging -> Focal and global Gmsclerosis Collapsing, tip // IgM deposit -> FSGS 가능성 더 큼

Treatment - Adult Prednisolon 4개월 이상 치료시 90%에서 관해 50-65%는 재발, 10-25%는 재재발 단백뇨는 2-3주 사이 완전관해, 부분적으로 관해 확인되면 Misdiagnosis 확률 높음 Initial 1mg/kg (Max 80mg/day), 12-16주, 6개월간 Tappering 단기 치료시 재발 가능성 커짐 Steroid-sensitive pt.의 경우 Side 적으면 1개월 Full dose Tx. 후 1개월간 Tappering 하기도 함. 재발이 자주 발생하는 Side 적은 환자는 15mg alternate day로 Low dose Tx. 하기도 함. 상기 치료시 재발할 경우 주당 5mg씩 안정적 관해 이루어질 때까지 증량

Treatment - Adult Frequent relapses + Avoidance of Steroid Oral cyclophosphamide > Cyclosporine Initial dose 2mg/kg/day, 12 weeks Leukocyte count에 따라 용량 조절 Frequent relapses + Initial Cyclophosphamide Cyclosporine, tacrolimus, Low dose prednisone 시도가능 Cyclophosphamide, Cyclosporine, 시도 후 안될시 Rituximab 시도 가능 375mg/m^2 6개월 후 두번째 시도 가능

Referance UPTODATE