단백뇨 소견을 보인 27세 남자 환자 R3 박선희/Prof. 임천규

M/27. 만성 B형 간염 진단 받은 자로 02년도 고대 병원에서 단백뇨 11637416 김O태 (M/27) Adm:2011.01.04 Chief Complaint Facial edema o/s) remote 3년 전 recent 한달 전 Present Illness M/27. 만성 B형 간염 진단 받은 자로 02년도 고대 병원에서 단백뇨 소견으로 renal biopsy 시도하였으나 실패하였던 과거력 있음. 내원 3년 전부터 과로시마다 facial edema소견 보였으며 한달 전부터 상기 소견 악화되어 local clinic 방문하여 시행한 검사상 단백뇨, 혈뇨 보여 자세한 검사위해 본원 내원.

Past Medical history Personal History Family History DM / HTN / Tb / Hepatitis ( - / -/ - / +) Chronic hepatitis B (+) : 수직감염 Op Hx(+) : Lt . Shoulder dislocation op (2005년) Medication : local clinic에서 이뇨제 처방받아 복용 Herbal medication : none Personal History Smoking (-) Alcohol (+): 주1회, 소주 2병 Family History 어머니 : Chronic hepatitis B, HTN

Preclinical course 2002.9 2002. 12 2010.12.20 2011.1.4 CHB 고대병원 본원 IN OPD 본원 IN OPD Adm U/A Protein (+~2+) Occult blood (3+) mRBC 30-60/HPF 24hr Urine Protein 496mg/d C3 72.9 mg/dL C4 12.3 mg/dL HBe Ag (+) Chemistry BUN/Cr 11/0.8 mg/dL U/A Protein (-) Occult blood (3+) mRBC 10-29/HPF Chemistry Pro/Alb 4.2/2.2 g/dL AST/ALT 93/97 IU/L BUN/Cr 10/1.0 mg/dL U/A Protein (3+) Occult blood (2+) mRBC 2-4/HPF Microscopic hematuria IG consult

Review of System General generalized weakness (-) fatigue (-) facial edema (+) febrile sense (-) chilling (-) weight change (-) Skin rash (-) itching (-) pigmentation (-) Eye & ENT visual disturbance (-) otalgia(-) rhinorrhea(-) sore throat(-) Respiratory cough (-) sputum (-) dyspnea (-) tachypnea (-) Cardiac chest pain (-) palpitation (-) orthopnea (-)

Review of System Gastrointestinal A/N/V/D/C (-/-/-/-/-) dysphagia (-) abdominal pain (-) hematemesis (-) hematochezia (-) melena (-) Urinary dysuria (-) frequency (-) urgency (-) gross hematuria (-) residual urine sense (-) flank pain (-) Musculoskeletal & Extremities myalgia (-) LBP(-) both leg edema (+ / +) Neurologic syncope (-) seizure (-) numbness (-)

Physical Examination Vital sign 120/80 mmHg – 84회/min – 20회/min – 36.6 °c Ht: 171cm Wt: 57kg (BMI: 19.5 kg/m2) General alert consciousness not so ill - looking appearance Skin rash(-) pigmentation(-) petechiae(-) Head & Neck neck vein engorgement (-) neck LN enlargement (-) Eye & ENT isocoric pupil with PLR (++/++) whitish sclera pinkish conjunctiva

Physical Examination Thorax Clear breathing sound without rale, wheezing Regular heart beat without murmur Abdomen Soft and flat abdomen Normoactive bowel sound No tenderness / rebound tenderness No palpable mass No splenomegaly no hepatomegaly Back & Extremities CVA tenderness (-/-) pretibial pitting edema (+/+) motor: V V sensory: 100 100 V V 100 100

Initial lab finding CBC/DC Chemistry 6,730/mm² - 13.7 g/dl – 43.0% - 210K (seg 58.1%) PT (INR) 1.01 aPTT 34.7 Chemistry TB 0.44 mg/dL Prot/Alb 4.0/2.1g/dL( A/G ratio 1.1 ) AST/ALT 170/173 IU/L ALP/GGT 62/67 IU/L BUN/Cr 17/0.9 mg/dL Na/K/Cl 141/4.0/104 mmol/L CRP <0.3 mg/dl Uric acid 5.4 mg/dL Ca/P/Mg 7.6/5.0/2.1 mg/dL ( Corrected Ca : 9.1 mg/dL ) Cholesterol 497 mg/dl Glucose 103 mg/dl LD/CK 520/2297 U/L U/A Occult blood (2+) Protein (3+) Glucose (-) Leukocytes (-) Nitrite (-) RBC 5-9/HPF WBC 0-1/HPF

Chest X-ray (2011.1.4)

EKG (2011.1.4) .Normal sinus rhythm .Rightward axis

Initial problem lists #1. facial edema, pretibial pitting edema #2. proteinuria #3. microscopic hematuria #4. hypoalbuminemia #5. hypercholesterolemia #6. elevated LFT #7. elevated CK, LDH #8. h/o chronic hepatitis B Nephrotic syndrome Acute exacerbations

Initial Assessment #1. Nephrotic syndrome #2. h/o chronic hepatitis B r/o MCD r/o MGN r/o IgA nephropathy r/o PSGN r/o MPGN #2. h/o chronic hepatitis B r/o acute exacerbation d/t drug d/t alcohol d/t other viral infection

Initial Diagnostic & Therapeutic Plan #1. Nephrotic syndrome D> Spot urine protein to creatinine ratio 24h urine collection Abdomen US Serologic marker (complement level, ANCA, ANA, immunoglobulin, cryoglobulin, ASO titer) viral marker Dysmorphic RBC, urine MCV if needed, Renal biopsy T> If no renal a. , stenosis  ARB Diuretics

Initial Diagnostic & Therapeutic Plan #2. Chronic hepatitis B D> Viral marker, tumor marker ( HBs Ag, Anti-HBs Ab, Anti-HBc Ab, Anti-HBe Ab, HBe Ag, HBV DNA Titer, anti-HAV Ab, anti-HCV Ab ) Abdomen US T> Antiviral agent

Clinical course

Abdomen & renal doppler (2011.1.5) 11.5cm 11.5cm Rt kidney 11.5cm , Rt RI 0.5 Lt kidney 11.5cm

Viral markers HBsAg (+) Anti-HBs Ab (-) Anti-HBc Ab Anti-HCV Ab Anti-HIV Ab Anti-HAV IgG VDRL Serologic marker IgG (mg/dL) 343 IgA (mg/dL) 119 IgM (mg/dL) 88.5 C3 (mg/dL) 91 C4 (mg/dL) 13.1 RA factor (IU/mL) 10.1 ASO titier 50.9 ANA - P-ANCA C-ANCA Cryoglobulin HBeAg (+) Anti HBe Ab (-) Real time PCR >9.89 x 108 copies/mL Tumor marker AFP 2.57

Urine RBC morphology <5% Urine MCV 88.2 fl Urine MCV/serum MCV = 88.2/84.1 =1.04 Urine RBC morphology <5% Spot urine Protein/Cr ratio = 700/161 = 4.35 g/day 24hr urine collection CrCl 75 ml/min Total urine volume 3320 ml 24hr urine protein 5607 mg/d 24hr urine Cr 1195 mg/d

Renal biopsy 2011.1.5

200배 PAS

x400

C1q C3 Fibrinogen IgA IgG IgM

U END CL

LM Ⅰ. Glomerulus Ⅱ. Tubulointerstitium 1. Number of Glomerulus: 8 2. Glomerulosclerosis (GS): (Y) 3 / 8 (%) Global glomerulusclerosis: 3 / 8 (%) 3. Capillary wall thickening: 3 4. Lumen of capillary: obliteration, focal 5. Capsular adhesion: (Y) 4 / 8 (%) 6. Duplication(Tram-track) of capillary wall: 2 7. Wire-loop formation of capillary wall: 0 8. Intraluminal hyalinosis: 0 9. Capillary necrosis: 0 10. Mesangial matrix expansion: 3 11. Mesagnial cell proliferation: 3 12. Mesangiolysis: 0 13. Inflammatory cell infiltration: 0 14. Crescent: (Y) 1 / 8 (%) Cellular cresent: 1 / 8 (%) 15. Glomerulitis: 0 16. Periglomerular fibrosis: (Y) 3 / 8 (%) Ⅱ. Tubulointerstitium 1. Mononuclear cell infiltration: 3 2. Neutrophilic infiltration: 0 3. Interstitial fibrosis: 3 4. Tubular atrophy: 3 5. Acute tubular necrosis: 0 6. Tubular cast: 1 7. Tubulitis (No/tubule): 1 Ⅲ. Vessels 1. Vasculitis, endotheliitis: 0 2. Necrosis: 0 3. Intraluminal thrombi: 0 4. Art. intimal hyalinosis: 0 5. Art. medial nodular hyalinosis: 0 6. Fibrous wall thickening: 0

IF C1q 12/12 - ++ C3 + IgA +/- IgG +++ IgM Antisera Number G.linear G.granular Mesangial GCW Tubules Interstitium Vessels C1q 12/12 - ++ C3 + Fibrinogen IgA +/- IgG +++ IgM

EM Diagnosis) Focal proliferative glomerulonephritis Ⅰ. Glomerulus 1. Epithelium 1) Foot process effacement (Y, diffuse) 2) Deposits (N) 2. GBM 1) Thickness (nm) - thickening 2) Contour - no pathologic abnormality 3) Texture- no pathologic abnormality 4) Deposits (Y) - location: intramembranous, subendothelial - type: immune type 3. Mesangium: Deposits, increase of mesangial matrix 4. Endothelium: No pathologic abnormality Diagnosis) Focal proliferative glomerulonephritis

PCR Cr Renal biopsy 2011.1.5 2011.1.17 2011.3 2011.6 2011.8 2011.12 2012.3 2012.6.18 exforge Olmesartan 20mg qd thiazide Entecavir 0.5mg qd DNA titer copies/ml ALT AST

Final diagnosis #1. MPGN, type I a/w hepatitis B infection #2. Chronic hepatitis B