1. KTP 후 신기능 저하로 내원한 28 세 남자 신장내과 pf. 이태원 / R2 황인경

2.  Chief complaint elevated creatinine  Present illness M/28, 1996 년 HSP 진단, 1998 년 RPGN 진단 후 ESRD 로 진행하여 1999 년 3 월 HD 시작했으며 2000 년 첫 번째 KTP 시행한 환자임. (donor : mother) 2002 년 chronic rejection 으로 2005 년부터 HD 재개 하였으며 2011 년 3 월 deceased donor 로부터 두 번째 KTP 받음. 이후 2011 년 5 월 acute rejection imp. 하 MPD pulse therapy 시행후 퇴원하였으나 creatinine 재상승하여 검사 위해 입원. 11370867 오 O 호 (M/28) Adm date : 2011.06.01

3.  Past Medical History DM/HTN/TB/Hepatitis(-/+/-/-) : 12 년 전 진단 HSP ESRD s/p KTP #2 Medication : PDL 10mg qd, Taclorimus 3mg bid, Mycophenolate 720mg bid Madipine 10mg qd  Personal History Smoking(-) Alcohol(-)  Family History  Operative History 2000 년 7 월 KTP (donor : mother)  2011 년 3 월 KTP (donor : deceased ) pRBC 2 pints transfusion

4. Past medical History 1996~2011 19961998.10 1999.032000.07 2002.03 2005.12 2011.03 MPD 1g pulse Tx. plasmapheresis RPGN HSP HD1 st KTP Renal Bx 1.Chronic tubulointerstitial infla. 2.Glomerualr sclerosis Renal Bx 1.Chronic tubulointerstitial infla. 2.Glomerualr sclerosis HD2 nd KTP 2005.07 MPD 1g pulse Tx 1.0 4.8 1.8 2.6 6.3 12.5 10.3 1.2 2.32.2 2.8 3.6 4.2 10.8 12.0 15.0 16.0 PRA class I 84% (anti Bw4 CREG, A1, A29, Cw2) PRA class II 0% HLA cross matching (-) BKV PCR : Urine (-), Plasma (-) CMV IgG (+), IgM (-) tacrolimus level 4~5 ng/mL PRA class I 84% (anti Bw4 CREG, A1, A29, Cw2) PRA class II 0% HLA cross matching (-) BKV PCR : Urine (-), Plasma (-) CMV IgG (+), IgM (-) tacrolimus level 4~5 ng/mL RecipientDonor A+A+ A+A+ RecipientDonor HLA A311HLA A211 HLA B350HLA B762 HLADR411HLA DR112

5. Past medical History 4.4 1.7 2.9 Renal Bx2 nd KTP MPD 1g pulse Tx 5/63/17 2.0 1.3 1.4 1.5 Viral marker (5/6) Serum CMV PCR (+) CMV antigenemia (-) & culture (-) BK virus PCR Plasma (-), Urine (+) Urine decoy cell : not observed Tacrolimus 3mg bid Mycophenolate 720mg bid PDL 50mg  10mg bid

6. Renal Biopsy (2011/5/6)

7. I. Glomerulus 1. Number of Glomerulus: 13 2. Glomerulosclerosis (GS): (N) 3. Capillary wall thickening: 0 4. Lumen of capillary: intact 5. Capsular adhesion: (N) 6. Duplication(Tram-track) of capillary wall: 0 7. Wire-loop formation of capillary wall: 0 8. Intraluminal hyalinosis: 0 9. Capillary necrosis: 0 10. Mesangial matrix expansion: 0 11. Mesagnial cell proliferation: 0 12. Mesangiolysis: 0 13. Inflammatory cell infiltration: 0 14. Crescent: (N) 15. Glomerulitis: 0 16. Periglomerular fibrosis: (N) Ⅱ. Tubulointerstitium 1. Mononuclear cell infiltration: 2 2. Neutrophilic infiltration: 0 3. Interstitial fibrosis: 0 4. Tubular atrophy: 0 5. Acute tubular necrosis: 0 6. Tubular cast: 0 7. Tubulitis (No/tubule): 0 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 Diagnosis : 1. Chronic tubulointerstitial inflammation 2. No specific alteration, glomerulus Diagnosis : 1. Chronic tubulointerstitial inflammation 2. No specific alteration, glomerulus Immunohistochemical finding: C4d (-), BK virus (-) Immunohistochemical finding: C4d (-), BK virus (-)

8.  General fatigue(-) general weakness(-) fever (-) chills(-) weight change(-) sweating (-)  Skin rash(-) itching(-) pigmentation(-)  H&ENT headache(-) stiffness(-) sore throat(-) rhinorrhea (-) nasal obstruction (-) otorrhea(-)  Respiratory cough(-) sputum(-) dyspnea(-)  Cardiac angina(-) palpitation(-) orthopnea(-) exertional dyspnea(-) Review of System

9.  Gastrointestinal anorexia (-) nausea (-) vomiting(-) diarrhea (-) constipation(-) abdominal pain(-) bowel habit change(-) melena(-) hematochezia(-)  Genitourinary dysuria(-) hematuria(-) frequency(-) oliguria(-) hesitency(-) urgency(-) residual urine sensation(-)  Musculoskeletal edema (-/-) weakness (-/-)  Neurologic dizziness (-) pph. numbness (-)

10. V/S 120/80 mmHg- 100 회 / 분 - 20 회 / 분 -36.5°C Ht 175.6cm, Wt 62.8kgBMI 20.4 Kg/m2 1.General Alert consciousness not so-ill looking appearance 2.Skin No rash or pigmentation Normal skin turgor 3.Head and Neck Normocephaly No thyroid enlargement No neck vein engorgement 4.Eye/ENT Isocoric pupil and PLR (++/++) pinkish conjunctivae whitish sclerae PI (-) PTH (-/-) Physical Examination

11. 5.Thorax Symmetric chest expansion Clear breathing sound without rale Regular heart beat without murmur 6. Abdomen Soft and flat abdomen Normoactive bowel sound Td/rTd (-/-) No hepatosplenomegaly 7.Back / Extremity CVA tenderness (-/-) pretibial pitting edema (-/-) 8.Neurology Sensory Motor 100 Ⅴ Ⅴ Ⅴ Ⅴ

12. Lab finding  CBC/DC 4190/mm² - 10.6 g/dl – 32.2% - 234K (seg. 86.7%)  Chemistry AST/ALT /ALP 16/17/67 IU/L BUN/Cr 40/2.8 mg/dL Na/K/Cl 137/4.1/104 mmol/L Ca/P/Mg 8.0/3.0/2.0mg/dL Glucose 110 mg/dL Prot/Alb 5.9/3.6 g/dL CRP 0.46mg/dL  UA RBC 2-4 /HPF WBC 0-1/HPF Glucose (-) nitrite (-) proteinuria (-) Cr 1.3  2.8 eGFR 70.5  28.9 FENa 1.51% FEUrea 27.2% Cr 1.3  2.8 eGFR 70.5  28.9 FENa 1.51% FEUrea 27.2%

13. Chest X-ray

14. EKG

15. Problem lists 1. Acute allograft dysfunction 2. HTN 3. Anemia I.Prerenal Hypotension Volume depletion II.Postrenal Urinary bladder dysfunction Ureteral obstruction III. Renal Acute rejection Cyclosporine, tacrolimus nephrotoxicity Infection, such as CMV, BK virus Recurrence of the primary disease I.Prerenal Hypotension Volume depletion II.Postrenal Urinary bladder dysfunction Ureteral obstruction III. Renal Acute rejection Cyclosporine, tacrolimus nephrotoxicity Infection, such as CMV, BK virus Recurrence of the primary disease

16. Initial assessment #1. Acute allograft rejection r/o Infection (BK virus-induced nephropathy, CMV infection) r/o Tacrolimus nephrotoxicity r/o Recurrence of the primary disease #2. HTN #3. Anemia

17. Initial assessment & plan #1. Acute allograft rejection r/o infection (BK virus-induced nephropathy, CMV infection) r/o Tacrolimus nephrotoxicity r/o Recurrence of the primary disease Diagnostic Plan) Renal doppler sono Viral marker study - BK virus PCR (urine, serum), urine decoy cell CMV PCR, CMV antigenemia, CMV culture Tacrolimus level check Renal Biopsy Therapeutic Plan) MPD pulse therapy + increase immunosuppressants dose antiviral angent + decrease immunosuppressants dose

18. Initial assessment & plan #3. HTN Therapeutic Plan) Madipine 10mg qd 유지 #4. Anemia Diagnostic Plan) serum iron, TIBC, Ferritin vitamin B12, folate reticulocyte, PBS, stool occult blood Therapeutic Plan) ferrous sulfate vitamin B12, folate

19. Renal doppler sono

20. Lab finding  CMV PCR : 5/2 (+)  6/1 (+)  CMV antigenemia (-)  CMV IgM (-), IgG (+)  CMV culture (-)  Urine Decoy cell : suspicious of decoy cells  PRA class-I : 82% (anti Bw4 CREG, A1, A29, Cw2) PRA class-II : 0%  Taclorimus level : 3.5ng/mL (6/1)

21. Renal Biopsy (2011/6/2)

22. I. Glomerulus 1. Number of Glomerulus: 10 2. Glomerulosclerosis (GS): 1/10 (%) 3. Capillary wall thickening: 0 4. Lumen of capillary: intact 5. Capsular adhesion: (N) 6. Duplication(Tram-track) of capillary wall: 0 7. Wire-loop formation of capillary wall: 0 8. Intraluminal hyalinosis: 0 9. Capillary necrosis: 0 10. Mesangial matrix expansion: 0 11. Mesagnial cell proliferation: 0 12. Mesangiolysis: 0 13. Inflammatory cell infiltration: 0 14. Crescent: (N) 15. Glomerulitis: 0 16. Periglomerular fibrosis: (N) Ⅱ. Tubulointerstitium 1. Mononuclear cell infiltration: 3 2. Neutrophilic infiltration: 0 3. Interstitial fibrosis: 0 4. Tubular atrophy: 0 5. Acute tubular necrosis: 0 6. Tubular cast: 0 7. Tubulitis (No/tubule): 0 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 Diagnosis : 1. Chronic tubulointerstitial inflammation Immunohistochemical finding: C4d (-), CMV virus (-) Immunohistochemical finding: C4d (-), CMV virus (-)

23. PDL 40mg  20mg Clinical course P- BK PCR 542,012copi/ml (5.73log) 460,476 (5.66log) 1,563,640 (6.19log) 27,486 ( 4.44 log) <700 U- BK PCR 12,218,552,620 (10.09log) 3,290,357,862 (9.52log) 29,019,108 (7.46log) 143,584 (5.16log) 200,900 (5.30 log) 33,860 (4.53log) Tacrolimus 3mg bid2mg bid mycophenolate 720mgbid Leflunomide 20mg bid Cyclosporine 100mg bid 360mg bid 5mg eod 7/24 Renal Bx. 2.8 1.7 3.0 3.6 4.2 2.6 2.4 2.2 MPD 1g pulse Tx Cidofovir 67kgx0.5mg q2wksGancyclovir for 3wks

24. Renal Biopsy (2011/7/25)

25. I. Glomerulus 1. Number of Glomerulus: 5 2. Glomerulosclerosis (GS): (N) 3. Capillary wall thickening: 0 4. Lumen of capillary: intact 5. Capsular adhesion: (N) 6. Duplication(Tram-track) of capillary wall: 0 7. Wire-loop formation of capillary wall: 0 8. Intraluminal hyalinosis: 0 9. Capillary necrosis: 0 10. Mesangial matrix expansion: 0 11. Mesagnial cell proliferation: 0 12. Mesangiolysis: 0 13. Inflammatory cell infiltration: 0 14. Crescent: (N) 15. Glomerulitis: 0 16. Periglomerular fibrosis: (Y) 1/5 (%) Ⅱ. Tubulointerstitium 1. Mononuclear cell infiltration: 4 2. Neutrophilic infiltration: 0 3. Interstitial fibrosis: 2 4. Tubular atrophy: 3 5. Acute tubular necrosis: 0 6. Tubular cast: + 7. Tubulitis (No/tubule): 3 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 Diagnosis : Consistent with acute cellular rejection, type IB Immunohistochemical finding: C4d (-), BK virus (-), CMV (-) Immunohistochemical finding: C4d (-), BK virus (-), CMV (-)

26. PDL 40mg  20mg Clinical course Tacrolimus 3mg bid2mg bid Mycophenolate 720mg bid leflunomide 20mg bid Cyclosporin 100mg bid Tacrolimus 2mg bid Mycophenolate 720mg bid 360mg bid 5mg eod 7/24 Renal Bx. PDL 5mg qd 2.8 1.7 3.0 3.6 4.2 2.6 2.4 2.2 P- BK PCR -- 542,012copi/ml (5.73log) 460,476 (5.66log) 1,563,640 (6.19log) 27,486 ( 4.44 log) --- U- BK PCR 12,218,552,620 (10.09log) 3,290,357,862 (9.52log) 29,019,108 (7.46log) 143,584 (5.16log) 200,900 (5.30 log) 33,860 (4.53log) 1,820 (3.25log) MPD 1g pulse Tx Cidofovir 67kgx0.5mg q2wks MPD 750mg pulse Tx Gancyclovir for 3wks

27. 3/17 5/4-5/10 8/82012/4/12 6/1-6/96/237/24 2 nd KTP Steroid pulse Tx #1 (5/4-5/7) Tubulointestitial inflammation Steroid pulse Tx #2 (6/1-6/4) BKV(+) Cidofovir 67kgx0.5mg q2wks Steroid pulse Tx#3 (8/3-8/7) 1.4 3.0 2.0 1.7 2.9 1.3 4.2 2.4 1.9 Clinical course 2011.03.17-2012.4.18 3/165/66/26/237/67/218/48/1710/26 P-BKV--5.73log5.66log6.19log4.44 log--- U-BKV-6.99log10.09log9.52log7.49log5.16 log5.30 log4.53log3.25log Cr 2.2 3.0 12/1910/268/26 2.0 Acute cellular rejection.

28. Final diagnosis #1.BK virus-induced nephropathy c Acute cellular rejection c Acute cellular rejection #2. CMV infection #3. HTN #4. Anemia of chronic illness