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Update in Transplantation Jeffrey J. Kaufhold, MD FACP Nephrology Associates December 2003.

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Presentation on theme: "Update in Transplantation Jeffrey J. Kaufhold, MD FACP Nephrology Associates December 2003."— Presentation transcript:

1 Update in Transplantation Jeffrey J. Kaufhold, MD FACP Nephrology Associates December 2003

2 Update in Transplantation Summary Trends in Survival after transplant Trends in Survival after transplant Expanded Donor Kidneys Expanded Donor Kidneys Waiting list Management changes Waiting list Management changes Trends in IS protocols Trends in IS protocols Kidney Pancreas Update Kidney Pancreas Update Ethnic Disparities in Transplants Ethnic Disparities in Transplants Immunology and Tolerance Immunology and Tolerance New approach to Complications New approach to Complications

3 Scope of problem 300,000 dialysis patients in US 300,000 dialysis patients in US 55,000 patients on waiting List 55,000 patients on waiting List 17,000 recovered kidneys per year 17,000 recovered kidneys per year from deceased donors from deceased donors 6000 from living related donors 6000 from living related donors 1000 kidneys not used after recovery 1000 kidneys not used after recovery Average waiting time 5 years ! Average waiting time 5 years !

4 Survival after Transplant Patient Survival 1 yr Patient Survival 1 yr LRD98% LRD98% DD95 DD95 Allograft Survival 1 yr Allograft Survival 1 yr LRD95% LRD95% DD89 DD89 Allograft half-life Allograft half-life LRD 21 years LRD 21 years 5 yrs 5 yrs LRD 91 % DD81 5 years 5 years LRD76% DD61 DD 13.8 years

5 Transplant survival Relative risk of death Relative risk of death Transplanted in 1993 = 1.0 Transplanted in 1993 = 1.0 Transplanted in1998 = 0.74 Transplanted in1998 = 0.74 Currently on Wait list= 1.7 Currently on Wait list= 1.7 These are the healthy ones! These are the healthy ones! Patients not on wait list = 2.6 Patients not on wait list = 2.6

6 Transplant Update Annual Death Rates Annual Death Rates Pts on list6.3 % Pts on list6.3 % Diabetic pts on list 10.8 % Diabetic pts on list 10.8 % Pts not on list21 % Pts not on list21 % Note that death censored graft loss is standard measure used in transplant outcome reports since this is desired outcome. Note that death censored graft loss is standard measure used in transplant outcome reports since this is desired outcome.

7 Risk of Graft Loss Higher risk Higher risk Deceased donor Deceased donor Recipient over 60 Recipient over 60 Donor over 60 Donor over 60 Recipient race Recipient race Black / Hispanic Black / Hispanic Long Cold Ischemic time Long Cold Ischemic time Previous Txp Previous Txp High PRA High PRA Lower Risk Lower Risk Living donor Recipient under 60 Donor under 60 Recipient race Asian Short cold ischemia Higher HLA match Low PRA

8 Expanded Donor Kidneys Used when risk of Txp is better than life expectancy on dialysis Used when risk of Txp is better than life expectancy on dialysis Criteria Criteria Recipient/donor over 60 Recipient/donor over 60 Diabetics over 40 Diabetics over 40 Failing access for dialysis Failing access for dialysis Patient with poor Quality of Life Patient with poor Quality of Life

9 Transplant Update HLA Matching HLA Matching Main HLA groupsA B C D Main HLA groupsA B C D C not important for transplant survival C not important for transplant survival Host of minor antigens Host of minor antigens Most important antigens are B and D Most important antigens are B and D D antigen is inducible and responsible for more serious (vascular) rejections D antigen is inducible and responsible for more serious (vascular) rejections

10 Waiting list management Point system for UNOS Wait list Point system for UNOS Wait list 1 pt per year on list 1 pt per year on list 7 pts for 0 mismatch with B, DR antigens 7 pts for 0 mismatch with B, DR antigens 5 pts for 1 mm with B, DR 5 pts for 1 mm with B, DR 2 pts for 2 mm with B, DR 2 pts for 2 mm with B, DR 4 pts for match in pt with PRA > 80 % 4 pts for match in pt with PRA > 80 % 4 pts for Age < 11, 3 pts for age pts for Age < 11, 3 pts for age National sharing of 0 mismatch kidneys National sharing of 0 mismatch kidneys % of all transplants % of all transplants

11 Wait list Management Ethnic disparity in rates of transplant Ethnic disparity in rates of transplant Due to smaller pool of B antigens in AA population Due to smaller pool of B antigens in AA population UNOS is changing point system to reflect this UNOS is changing point system to reflect this Eliminating points for B antigen reduces the ethnic disparity in points awarded. Eliminating points for B antigen reduces the ethnic disparity in points awarded.

12 Trends in Transplantation Rejection rates and Creatinine at 6 months are now surrogates for allograft survival Rejection rates and Creatinine at 6 months are now surrogates for allograft survival Due to improved survival, a study of a new drug would need over 9000 enrollees to show a difference. Due to improved survival, a study of a new drug would need over 9000 enrollees to show a difference. Rejection rates are down 50 % Rejection rates are down 50 % Cardiovascular death rate improving. Cardiovascular death rate improving.

13 Trends in Transplantation Overall Mortality is unchanged! Overall Mortality is unchanged! Death with functioning graft increasing Death with functioning graft increasing Donor Age older Donor Age older Recipient age is older Recipient age is older Time on waiting list is longer Time on waiting list is longer Older, sicker patients are getting transplants Older, sicker patients are getting transplants

14 Induction Immunosuppression Biological Agents Biological Agents Steroid use vs steroid sparing Steroid use vs steroid sparing Cellcept used in place of Imuran Cellcept used in place of Imuran Calcineurin Inhibitors / Sirolimus Calcineurin Inhibitors / Sirolimus

15 Induction Immunosuppression Biological Agents Biological Agents OKT-3 rarely used OKT-3 rarely used Thymoglobulin (rabbit) Thymoglobulin (rabbit) ATG (polyclonal) ATG (polyclonal) Basiliximab (Simulect) Chimeric Basiliximab (Simulect) Chimeric Anti CD 25/ anti IL-2 receptor monoclonal Anti CD 25/ anti IL-2 receptor monoclonal Daclizumab (Zenapax) Humanized Daclizumab (Zenapax) Humanized Anti CD 25 Monoclonal Anti CD 25 Monoclonal

16 Induction Immunosuppression Biological Agents Biological Agents Expensive, complex to use Expensive, complex to use Use in high risk patients: Use in high risk patients: High PRA High PRA Second transplant Second transplant African American recipient African American recipient Delayed Graft function Delayed Graft function

17 Induction Immunosuppression Biological Agents Biological Agents Basiliximab and Daclizumab Basiliximab and Daclizumab Anti CD 25 monoclonals Anti CD 25 monoclonals Do not deplete lymphocytes Do not deplete lymphocytes Will not stop ongoing rejection Will not stop ongoing rejection Other immunosuppression (CNI, steroid, MMF) should continue during use Other immunosuppression (CNI, steroid, MMF) should continue during use OKT-3, ATG OKT-3, ATG Deplete lymphocytes, stop rejection, Deplete lymphocytes, stop rejection, reduce or withhold other immunosuppression while in use reduce or withhold other immunosuppression while in use

18 Induction Immunosuppression New Biological Agents coming soon: New Biological Agents coming soon: CTL4 Ig CTL4 Ig stimulates CTL4 coreceptor on T cell which leads to stimulates CTL4 coreceptor on T cell which leads to Decreased activation Decreased activation Apoptosis of the activated cell line Apoptosis of the activated cell line LEA 29 Y LEA 29 Y a second generation CTL4 Ig a second generation CTL4 Ig

19 Regulation of T-Cell Activation APC T-Cell MHC TCR CD 40 CTL4 Negative stimulatory CD 80/86 CD 25 Positive stimulation IL -2 Receptor IL-2 Antigen

20 T cell Costimulation

21

22 Induction Immunosuppression Biological Agents recommendations Biological Agents recommendations Low risk patient: Low risk patient: IL-2 receptor antibody, consider steroid sparing regimen IL-2 receptor antibody, consider steroid sparing regimen High Risk patient High Risk patient Thymoglobulin plus 3 drug regimen Thymoglobulin plus 3 drug regimen CNI, Steroids, MMF CNI, Steroids, MMF

23 Maintenance Immunosuppression Categories of Agents: Categories of Agents: Steroids Steroids Calcineurin Inhibitors Calcineurin Inhibitors Intracellular signal modifiers Intracellular signal modifiers Cyclosporine, Tacrolimus, Prograf Cyclosporine, Tacrolimus, Prograf Adjuvant Agents Adjuvant Agents Interfere with cell cycling Interfere with cell cycling Sirolimus, Rapamicin Sirolimus, Rapamicin Cellcept (MMF) Cellcept (MMF) Imuran (azothioprine) Imuran (azothioprine)

24 Maintenance Immunosuppression Three Drug Regimen: Three Drug Regimen: Steroid - prednisone Steroid - prednisone Calcineurin Inhibitor Calcineurin Inhibitor Cyclosporine, Tacrolimus (Prograf) Cyclosporine, Tacrolimus (Prograf) Adjuvant Agent Adjuvant Agent Cellcept (MMF) Cellcept (MMF) Steroid Sparing Regimen: Steroid Sparing Regimen: Prograf + MMF or Rapamicin Prograf + MMF or Rapamicin

25 Drug Dosages Steroid Steroid 10 mg daily or every other day 10 mg daily or every other day CyA CyA 4-6 mg/Kg/day usually BID 4-6 mg/Kg/day usually BID Levels 1-6 months: Levels 1-6 months: Level after 6 months: 100 – 250 Level after 6 months: 100 – 250 Imuran Imuran 50 – 100 mg daily at bedtime 50 – 100 mg daily at bedtime

26 Drug Dosages Prograf Prograf 0.1 – 0.2 mg/kg/day 0.1 – 0.2 mg/kg/day Usually about 5 mg BID Usually about 5 mg BID Levels 5-15 by ELISA Levels 5-15 by ELISA Rapamicin Rapamicin 6 mg po load then 2 mg po daily 6 mg po load then 2 mg po daily Cellcept (MMF) Cellcept (MMF) 1000 mg BID, taper if low WBC or anemia, GI intolerance mg BID, taper if low WBC or anemia, GI intolerance.

27 Drug Conversion for Cause Refractory Rejection: CyA -> Tac Refractory Rejection: CyA -> Tac Cardiovasc Dz: CyA -> Tac Cardiovasc Dz: CyA -> Tac Rapa -> MMF Rapa -> MMF Diabetes:decrease steroid dose Diabetes:decrease steroid dose Tac -> CyA may be helpful Tac -> CyA may be helpful Hirsuitism: CyA -> Tac Hirsuitism: CyA -> Tac Gout: Azo -> MMF Gout: Azo -> MMF Gingival Hyperplasia: CyA -> Tac Gingival Hyperplasia: CyA -> Tac Stop dihydropyridines (procardia XL) Stop dihydropyridines (procardia XL)

28 Kidney – Pancreas Transplant

29 Cost: Cost: Kidney Txp:$ 60,000 Kidney Txp:$ 60,000 Islet cells 53,000 Islet cells 53,000 Panc Txp alone 105,000 Panc Txp alone 105,000 SPK (K-P) 130,000 SPK (K-P) 130,000 Each year on dialysis: $27,000 Each year on dialysis: $27,000

30 Kidney – Pancreas Transplant Rejection rates improved Rejection rates improved Options for pancreas placement: Options for pancreas placement: Attach to bladder Attach to bladder Dumps lots of bicarb, Cystitis Dumps lots of bicarb, Cystitis Easy to identify rejection by measuring urine amylase Easy to identify rejection by measuring urine amylase Attach to intestine (enteric anastomosis) Attach to intestine (enteric anastomosis) Eliminates problems with acidosis and cystitis Eliminates problems with acidosis and cystitis Rejection harder to identify early. Rejection harder to identify early.

31 Kidney – Pancreas Transplant Rejection Diagnosis: Rejection Diagnosis: Hyperglycemia Hyperglycemia May also occur in face of high steroids, sepsis May also occur in face of high steroids, sepsis Increased serum amylase level Increased serum amylase level Decreased urine amylase level in bladder anastomosis patients. Decreased urine amylase level in bladder anastomosis patients. Maintenance immunosuppression Maintenance immunosuppression Tacrolimus/Cellcept preferred combo Tacrolimus/Cellcept preferred combo Avoid steroids if possible Avoid steroids if possible

32 Kidney – Pancreas Transplant Surgical Complication rate 10% at 1 yr. Surgical Complication rate 10% at 1 yr. Immunologic Failure Rates: Immunologic Failure Rates: Type of Txp% graft loss at 1 yr. Type of Txp% graft loss at 1 yr. PAK7 % PTA8 SPK2 Gruessner, Clinical Transplantation 2002, p 52

33 Kidney – Pancreas Transplant Effect of Pancreas Txp on outcomes Effect of Pancreas Txp on outcomes No significant QOL improvement compared to kidney alone No significant QOL improvement compared to kidney alone Insulin free for diabetics 50 – 90 % Insulin free for diabetics 50 – 90 % Neuropathy improves Neuropathy improves Microvasculature improves Microvasculature improves Retinopathy – no improvement Retinopathy – no improvement Survival improved compared to wait list pts Survival improved compared to wait list pts May be slightly better than kidney alone. May be slightly better than kidney alone.

34 Ethnic Disparities in Transplant Rate of transplantation lower than any other ethnic group Rate of transplantation lower than any other ethnic group % of AA patients hearing about the option of transplant is only about 70% of other groups % of AA patients hearing about the option of transplant is only about 70% of other groups Rate of referral once they hear about transplant is only about 70% of other groups. Rate of referral once they hear about transplant is only about 70% of other groups.

35 Ethnic Disparities in Transplant Socioeconomic Factors: Socioeconomic Factors: 70% of AA children born into single parent homes 70% of AA children born into single parent homes Less likely to have insurance Less likely to have insurance Barriers to travelling to appts Barriers to travelling to appts Less likely to be available when called Less likely to be available when called No phone or wont answer due to debtors No phone or wont answer due to debtors Higher PRA, fewer AA donors Higher PRA, fewer AA donors Mistrust of system Mistrust of system

36 Ethnic Disparities in Transplant Insurance Impact on Transplant: Insurance Impact on Transplant: Compared to pts of other ethnic groups with same insurance, % of eligible AA pts get to transplant Compared to pts of other ethnic groups with same insurance, % of eligible AA pts get to transplant HMO rates % of eligible pts get to transplant, evenly across races HMO rates % of eligible pts get to transplant, evenly across races Example of Rationing by Inconvenience Example of Rationing by Inconvenience Military patients demonstrate NO disparity in rates of transplant or Graft survival. Military patients demonstrate NO disparity in rates of transplant or Graft survival.

37 Ethnic Disparities in Transplant Immunologic Factors Immunologic Factors Once transplanted, AA pts fare worse Once transplanted, AA pts fare worse AA with 0 MM does about as well as Caucasian with 6 MM and 1 rejection episode in first year. AA with 0 MM does about as well as Caucasian with 6 MM and 1 rejection episode in first year. Require higher doses of Immunosuppression Require higher doses of Immunosuppression Dont tolerate steroid or other drug withdrawal nearly as well as other groups Dont tolerate steroid or other drug withdrawal nearly as well as other groups Higher levels of IL-6, CD-80, TGF-B, Endothelin, Renin. Higher levels of IL-6, CD-80, TGF-B, Endothelin, Renin. More Hypertensive, which worsens overall survival More Hypertensive, which worsens overall survival

38 Rejection Clinical Diagnosis: Clinical Diagnosis: Hypertension Hypertension Increased Creatinine Increased Creatinine Decreased urine output Decreased urine output Biopsy findings: Biopsy findings: Tubulitis – usual Vasculitis - bad Tubulitis – usual Vasculitis - bad Interstitial infiltration Interstitial infiltration Fixing of C 4 d Fixing of C 4 d

39 Rejection Biopsy findings

40 Rejection and Complement Circulating Proteins in blood: Circulating Proteins in blood: #1Albumin #1Albumin #2Immunoglobulin #2Immunoglobulin #3Complement, esp C 3. #3Complement, esp C 3. Triggers of Complement fixation Triggers of Complement fixation Ischemia reperfusion injury (IP - 10) Ischemia reperfusion injury (IP - 10) Brain injury in donor Brain injury in donor Dialysis after transplant Dialysis after transplant Infection Infection

41 Immunology of Rejection HLA A and B are constitutive antigens HLA A and B are constitutive antigens HLA D is inducible antigen HLA D is inducible antigen Infection, ischemia induce D antigen expression Infection, ischemia induce D antigen expression D antigen expression leads to vascular rejection which is worst type D antigen expression leads to vascular rejection which is worst type How does Bactrim SS MWF help? How does Bactrim SS MWF help?

42 Immunology of Rejection HLA A and B are constitutive antigens HLA A and B are constitutive antigens HLA D is inducible antigen HLA D is inducible antigen Infection, ischemia induce D antigen expression Infection, ischemia induce D antigen expression D antigen expression leads to vascular rejection which is worst type D antigen expression leads to vascular rejection which is worst type Bactrim SS MWF reduces bacteriuria Bactrim SS MWF reduces bacteriuria

43 Immunology of Rejection HLA A and B are constitutive antigens HLA A and B are constitutive antigens HLA D is inducible antigen HLA D is inducible antigen Infection, ischemia induce D antigen expression Infection, ischemia induce D antigen expression D antigen expression leads to vascular rejection which is worst type D antigen expression leads to vascular rejection which is worst type Bactrim SS MWF reduces bacteriuria Bactrim SS MWF reduces bacteriuria What is Acyclovir used for after Txp? What is Acyclovir used for after Txp?

44 Immunology of Rejection HLA A and B are constitutive antigens HLA A and B are constitutive antigens HLA D is inducible antigen HLA D is inducible antigen Infection, ischemia induce D antigen expression Infection, ischemia induce D antigen expression D antigen expression leads to vascular rejection which is worst type D antigen expression leads to vascular rejection which is worst type Bactrim SS MWF reduces bacteriuria Bactrim SS MWF reduces bacteriuria Acyclovir reduces shedding of Herpes Simplex virus in urine Acyclovir reduces shedding of Herpes Simplex virus in urine

45 Immunology of Rejection Chemoattractant Cytokines (chemokines) Chemoattractant Cytokines (chemokines) Leukocyte recruitment Leukocyte recruitment Most important CK is CXC Most important CK is CXC Receptor is CXC-R3 Receptor is CXC-R3 Transmembrane protein Transmembrane protein Activation of CXC R3 activates rejection pathway Activation of CXC R3 activates rejection pathway IP-10 Activates CXC R3 IP-10 Activates CXC R3 Both CXC R3 and IP-10 are present in urine of pts who are rejecting Both CXC R3 and IP-10 are present in urine of pts who are rejecting

46 Immunology of Rejection The Future Chemokine receptors: Chemokine receptors: CXC R3 antibody prolongs graft survival in monkey models CXC R3 antibody prolongs graft survival in monkey models Also in clinical trials: CCR-1, CCR-5 which bind CKs and prevent activation of receptor. Also in clinical trials: CCR-1, CCR-5 which bind CKs and prevent activation of receptor. Soluble Complement Receptor CR-1 Soluble Complement Receptor CR-1 Trypriline decreases synthesis of complement Trypriline decreases synthesis of complement WY14643 ligand for PPAR WY14643 ligand for PPAR

47 Immunology of Rejection The Future Protein Tyrosine Kinases Protein Tyrosine Kinases Src Src FAK FAK Paxillin Paxillin Akt Akt PPARS peroxisome proliferator activated receptors PPARS peroxisome proliferator activated receptors Ligands for PPARs tend to decrease inflammatory response Ligands for PPARs tend to decrease inflammatory response Include Piaglitizone, Lopid Include Piaglitizone, Lopid

48 Immunology of Rejection Tolerance is the best immunosuppression Tolerance is the best immunosuppression Has been known for years Has been known for years First seen in pts treated with Steroids/Imuran First seen in pts treated with Steroids/Imuran Patients present off all IS with stable renal function, normal biopsy. Patients present off all IS with stable renal function, normal biopsy. Cyclosporine seems to impair development of tolerance Cyclosporine seems to impair development of tolerance Has lead to research about T-Cell coreceptors Has lead to research about T-Cell coreceptors

49 Tolerance Inducing Mechanisms T- Cell deletion in Thymus T- Cell deletion in Thymus Thy – 1 cells lead to rejection Thy – 1 cells lead to rejection Peripheral T- Cell deletion Peripheral T- Cell deletion IL-2 dependent IL-2 dependent FAS dependent FAS dependent Veto Cells Veto Cells So immune system activation is required but apoptosis is favored over rejection So immune system activation is required but apoptosis is favored over rejection Peripheral Non-deletional mechanism Peripheral Non-deletional mechanism Anergy – loss of response to antigen Anergy – loss of response to antigen Thy 2 cells – regulatory/suppressor cell Thy 2 cells – regulatory/suppressor cell

50 Tolerance in Practice Today For high PRA and Positive Crossmatch pts: For high PRA and Positive Crossmatch pts: IVIG/plasmapheresis before and after TXP IVIG/plasmapheresis before and after TXP Leads to decrease % Anti-donor antibody Leads to decrease % Anti-donor antibody After Txp, Antidonor Ab returns but does not lead to rejection After Txp, Antidonor Ab returns but does not lead to rejection Anergy Anergy Increase in Bcl - 2 Increase in Bcl - 2

51 Tolerance Tolerogenic Immunosuppression Tolerogenic Immunosuppression Rapamicin, Tacrilimus seem to be OK Rapamicin, Tacrilimus seem to be OK Cyclosporine blocks tolerance pathway Cyclosporine blocks tolerance pathway Starzl Lancet 2003 Starzl Lancet 2003 Sayegh Annals of Surgery 2003 Sayegh Annals of Surgery 2003

52 Complications of Transplant Hypertension Hypertension Correlates with Age Correlates with Age Diabetes Diabetes Race Race Graft Function Graft Function CNI use CNI use Steroids Steroids Graft Survival reduced if hypertension + Graft Survival reduced if hypertension +

53 Complications of Transplant Hypertension Hypertension Target SBP < 130 Target SBP < 130 Chronic Allograft Nephropathy Chronic Allograft Nephropathy Proteinuria Proteinuria Target BP 125 / 75 Target BP 125 / 75 Recommended Drugs: Recommended Drugs: B blockers B blockers ACE inhibitors ACE inhibitors CCBs and diuretics as needed. CCBs and diuretics as needed.

54 Complications of Transplant New Onset Diabetes after Txp New Onset Diabetes after Txp NODAT NODAT Decrease steroids if possible Decrease steroids if possible Consider Change from TAC to CyA. Consider Change from TAC to CyA. Cardiovascular Risk of a 25 y.o. recipient Cardiovascular Risk of a 25 y.o. recipient Equal to the risk for a 55 y.o. without renal disease. Equal to the risk for a 55 y.o. without renal disease. 10 fold higher at any age! 10 fold higher at any age!

55 Complications of Transplant Hyperlipidemia Hyperlipidemia Assume CV risk is present Assume CV risk is present LDL target < 100 LDL target < 100 Consider decreasing Steroids Consider decreasing Steroids Recommend changing CyA or Rapa to TAC. Recommend changing CyA or Rapa to TAC. Thrombin Activatable Fibrinolysis Inhibitor Thrombin Activatable Fibrinolysis Inhibitor TAFI levels are increased in Txp and Diabetes TAFI levels are increased in Txp and Diabetes Increase risk of DVT, Unstable Angina. Increase risk of DVT, Unstable Angina.

56 Complications of Transplant Post Transplant Bone Disease Post Transplant Bone Disease Osteoporosis in % of pts Osteoporosis in % of pts BMD decreases 6-10 % per year BMD decreases 6-10 % per year Fractures occurrence Rate Fractures occurrence Rate Diabetics:40-50 % Diabetics:40-50 % Non diabetics:10-15 % Non diabetics:10-15 % Contributing Factors: Contributing Factors: Renal osteodystrophy, Immunosuppressives Renal osteodystrophy, Immunosuppressives PTH, Age, Gender, Gonadal Status PTH, Age, Gender, Gonadal Status

57 Complications of Transplant Post Transplant Bone Disease Post Transplant Bone Disease Treatment Treatment Calcium 1200 mg Daily Calcium 1200 mg Daily Vit D 400 – 800 mcg daily Vit D 400 – 800 mcg daily Exercise, Tai Chi Exercise, Tai Chi Quit smoking! Quit smoking! Fosamax 70 mg week or 5 mg daily for 6-12 months. Fosamax 70 mg week or 5 mg daily for 6-12 months.

58 Update in Transplantation Summary Trends in Survival after transplant Trends in Survival after transplant Expanded Donor Kidneys Expanded Donor Kidneys Waiting list Management changes Waiting list Management changes Trends in IS protocols Trends in IS protocols Kidney Pancreas Update Kidney Pancreas Update Ethnic Disparities in Transplants Ethnic Disparities in Transplants Immunology and Tolerance Immunology and Tolerance New approach to Complications New approach to Complications


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