7-2 Transplantation Case-Based Discussion

Transcription

1 The 58 th JSN APSN Continuing Medical Education Course Transplantation Case-Based Discussion Tadashi Sofue, MD, PhD Division of Nephrology and Dialysis, Department of Internal Medicine, Kagawa University Hospital Division of Nephrology and Dialysis, Department of CardioRenal and CerebroVascular Medicine, Faculty of Medicine.

2 Statement of Disclosure The author does not have any financial conflict of interest regarding the material in this presentation.

3 Case Presentation Patient: 35-year-old Male Past History:Type-2 Diabetes (from 15 years old) Diabetic retinopathy Family History:Older sister: DM Mother: DM Present illness 15 y.o. Diagnosed with diabetes and hypertension (No treatment) 25 y.o. Treatment with sulfonylurea 30 y.o. Kidney dysfunction with nephrotic syndrome 34 y.o. Initiation of hemodialysis (HD) 35 y.o. He consulted our hospital for the purpose of a living-donor kidney transplantation from his father.

4 Status before KT Status Height:165 cm Body weight:72 kg BMI: 26.5 Blood pressure: 162/87 mmhg Heart rate:60/min Lung: clear, no rale. Heart: regular, no murmur Abdomen: soft and flat Leg edema: none, left forearm: AVF Patient background Occupational history: sake dealer (drank two cans of beer/day) Smoking history: years (stopped smoking before KT) Medication: Candesartan 8 mg 1 tab/day Amlodipine 5 mg 2 tab/day Doxazosin 2 mg 1 tab/day Lansoprazole 15 mg 1 tab/day

5 Laboratory Data before KT CRP 0.11 mg/dl TP 7.0 g/dl Alb 3.7 g/dl BUN 57.8 mg/dl Cr mg/dl Na 140 meq /L K 5.3 meq /L Cl 99 meq /L Ca 9.4 mg/dl IP 7.6 mg/dl T-bil 0.3 mg/dl GOT 3 U/L GPT 9 U/L ALP 229 U/L LDH 144 U/L GGTP 15 U/L CHE 222 U/L WBC 5,690 /μl RBC /μl Hb 11.0 g/dl Ht 34.1 % Plt /μl C3 70 mg/dl C4 27 mg/dl CH ANA 40 fold IgA 218 mg/dl IgG 1,237 mg/dl IgM 88 mg/dl ipth 152 pg/ml β2mg 24.7 mg/l HbA1c (NGSP) 6.7 %

6 Examination before KT CT: no malignancy Gastrointestinal endoscopy: n.p. Colorectal endoscopy: n.p. HCV-ab, HBV-ag: negative Chest Xp ECG Echo cardiography CTR = 44% Myocardial Ischemia? Sinus rhythm Left ventricular hypertrophy Ejection fraction: 49%, Wall motion: diffuse, mild hypokinesis

7 Donor Examination (1) Father (72 years old) Height: 168 cm Body weight: 72 kg BMI: 25.5 Smoking: 10/day 50 years Past history: hypertension Medication: Carvedilol 20 mg 1 tab/day Amlodipine 5 mg 1 tab/ day Blood pressure:128/70 mmhg Kidney function:cr 0.77 mg/dl egfr 75.7 ml/min/1.73 m 2 Urinary protein (dipstick): negative Urinary occult blood (dipstick): negative Urinary albumin excretion (UAE):16.7 mg/gcr

8 Gastrointestinal endoscopy: atrophic gastritis Immunochemical fecal occult blood test: negative ECG:within normal range UCG:EF 73%, no asynergy HCV-ab, HBV-ab: negative 99m Tc-MAG3 scintigraphy Donor Examination (2) Enhanced 3D-CT Split kidney function: right/left=48/52 No abnormality of renal artery or vein

9 Immunological Condition Histocompatibility test CDC XM : T( ) Bw ( ) Bc ( ) Flow XM : T( ) B( ) Flow PRA : class I (+) class II ( ) HLA mismatch: 3/6 Blood-type Incompatible (B+ O+) Recipient anti-b IgG 64-fold Recipient anti-b IgM 64-fold

10 Problems Associated with this Case Type-2 diabetes Possibility of myocardial ischemia Marginal donor with hypertension ABO-incompatible KT Indication or contraindication for LDKT?

11 Transplantation for Diabetic Patients Diabetic patients with ESRD Transplant with diabetes Waiting list with diabetes Factors aggravating BS control CNI PSL Weight gain Non-candidates with diabetes KT for diabetic patients markedly improves survival rates. Diabetic patients are not contraindicated for KT Sørensen VR, et al. Diabetologia 2007;50(5):922-9

12 Possibility of Myocardial Ischemia (1) Myocardial perfusion scintigraphy (Recipient) Negative Negative Myocardial perfusion imaging and degree of coronary artery stenosis CAD>70% Although a positive myocardial perfusion study is predictive of CAD (more than 70%), a poor negative predicted value (64.6%) was reported in cases of ESRD with DM. Welsh RC, et al. Transplantation 2011;91(2):213-8

13 CAG Possibility of Myocardial Ischemia (2) LVG No apparent stenosis was observed in his coronary artery. Wall motion: intact, EF 68% Overall, he showed a low risk of cardiovascular events in the peri-operative period.

14 Plasmapheresis for ABO-incompatible KT To prevent acute antibody-mediated rejection caused by antiblood-type antigen, we treat recipients before ABO-incompatible KT by antibody removal therapy (plasma exchange and doublefiltration plasmapheresis) and inhibition of antibody production.

15 Marginal Donor (living-kt) This donor candidate had many marginal factors Age > 70 years old egfr <80 (>70) ml/min Hypertension Two anti-hypertensive drugs UAE<30 mg/gcr Acceptable as a living-donor?

16 Living-donor Criteria in the World and Japan Amsterdam forum Marginal criteria in Japan Age Kidney function (ml/min/1.73 m 2 ) egfr 80 egfr 70 BMI 35 kg/m 2 32 kg/m 2 Hypertension 140/80 mmhg with less than 1 drug (age>50, UAE 30 ) 140/80 mmhg with no drug or 130/80 mmhg with less than 2 drugs + UAE 30 mg/gcr Proteinuria 300 mg/day 150 mg/day or UAE 30 mg/gcr Diabetes Excluded HbA1c 6.5% + UAE 30 mg/gcr Our donor candidate Age: 72 years old egfr: 76 ml/min/1.73 m 2 Hypertension Two anti-hypertensive drugs UAE: 17 mg/gcr Acceptable as living marginal donor Pre-transplant lifestyle modifying is also important Donor criteria for living-donor kidney transplantation in Japan 2014 Amsterdam Forum; Delmonico F, Transplantation. 2005;79(6 Suppl):S53-66

17 Living-donor KT from Hypertensive Donors with High-normal Albuminuria (15-30 mg/gcr) Hypertension and the degree of albuminuria did not affect the donor kidney function after donation. Recipients of hypertensive donors with high-normal albuminuria showed lower egfr than other recipients. Sofue T, et al. Transplantation 2014; 97(1):

18 Problems before KT Type-2 diabetes Suspected myocardial ischemia ABO incompatible Marginal donor (Hypertension, egfr) Indication for LDKT? YES (in Japan)

19 Clinical Course (1) HD Rituximab 200 mg DFPP mpsl (mg) MMF (mg) 1,000 2,000 1,500 Prolonged-release Tacrolimus: Trough 8-10 ng/ml HD HD HD DFPPPE Basiliximab S-Cr (mg/dl) Anti-B IgG titer 8 4 Kidney Transplantation Day -7 Day -5 Day -2 Tx Day 7 Day 14

20 Donor Nephrectomy Laparoscopy with hand assist Urologist Left kidney

21 Recipient Operation Preimplantation (0 h) biopsy at bench Recipient internal iliac artery Donor renal artery Donor renal vein Donor ureter Recipient common iliac vein Donor kidney After perfusion First-catch urine

22 HD Rituximab 200 mg DFPP Clinical Course (2) 500 mpsl (mg) MMF ( mg ) 1,000 2,000 1,500 Prolonged-release Tacrolimus: Trough 8-10 ng/ml HD HD HD DFPPPE Basiliximab S-Cr (mg/dl) Anti-B IgG titer 8 4 Kidney Transplantation no acute antibody-mediated allograft rejection was observed Day -7 Day -5 Day -2 Tx Day 7 Day 14

23 Preimplantation Allograft Biopsy Pathological diagnosis: Fibrous intimal thickening Global glomerular sclerosis 4/20 No IgA deposition C3

24 S-Cr (mg/dl) 2 1 Clinical Course (3) 4 mg mpsl 2 mg MMF 1,500 mg 1,000 mg Prolonged-release Tacrolimus: Trough (ng/ml) 4~6 Recipient HbA1c (%) OB ( ) ( ) (+) UP ( ) ( ) ( ) (+) (++) ( ) (++) 1 month 6 months 1 year 2 years 3 years S-Cr (mg/dl) 2 1 Donor Lifestyle modifying (stop smoking, reduce Na intake) 0.77 Donation UP ( ) ( ) ( ) ( ) ( ) ( ) pre 6 months 1 year 2 years 3 years

25 Episode Allograft Biopsy Indication for episode allograft biopsy 30% increase in Cr from baseline Urinary protein > 0.5 g/gcr Appearance of occult blood in the urine KDIGO Transplant Work Group, Am J Transplant. 2009; 9 Suppl 3: S Possible causes of urinary abnormality in this case Chronic antibody-mediated rejection CNI toxicity Recurrent diabetic nephropathy De novo (or unknown-origin) glomerulonephritis

26 Causes of Proteinuria after KT n=98, from China Modified from Sun Q, et al. PLoS One. 2012;7(5):e36654

27 Results of Allograft Biopsy (1) Banff score: t0,i1,g0,v0,ci2,ct2,cg0,cv0,ah3,aah1,mm3,ptc0 No acute rejection, severe IF/TA Arteriolar hyaline thickening (due to diabetes?) No CNI toxicity AUC study: Tac-ER AUC ng h/ml

28 Results of Allograft Biopsy (2) Post-transplant IgA nephropathy Mesangial expansion + IgA deposition in the mesangial domain with tuft necrosis (no crescent formation) We could not diagnose de novo or recurrent IgA nephropathy, because he did not undergo kidney biopsy before KT. How can we treat this case? IgA

29 Treatment for IgA Nephropathy in Native Kidney From Japan Tonsillectomy with steroid pulse therapy reduced proteinuria in cases of IgA nephropathy involving the native kidney. Kawamura T, et al. Nephrol Dial Transplant. 2014;29(8):

30 Treatment for Recurrent IgA Nephropathy NS Modified from Kennoki T, et al. Transplantation. 2009;88: Courtney AE, et al. Nephrol Dial Transplant. 2006;21(12): Tonsillectomy alone, without steroid pulse therapy, reduced proteinuria in patients with recurrent IgA nephropathy. An effect of ARB on the improvement of graft survival was not evident.

31 Clinical Course (4) Tonsillectomy S-Cr (mg/dl) 2 1 Recipient month MMF 1,500 mg mpsl 2 mg 1 year Insulin 1,000 mg Prolonged-release Tacrolimus: Trough (ng/ml) 4~6 HbA1c (%) OB ( ) ( ) (+) UP ( ) ( ) ( ) (+) (++) 6 months years mpsl 1,000 mg 4 mg PSL 20 mg Rb ( ) (++) years (+) (+) Tonsillectomy + steroid pulse therapy reduced urinary abnormality, although his blood glucose was aggravated.

32 Our case shows that: Summary Diabetes, ABO incompatibility, and marginal donor are not contraindications for living-donor kidney transplantation. Allograft biopsy is needed to diagnose the causes of post-transplant urinary abnormality. Participation of a nephrologist is needed to prolong graft survival.