Transplantation Dealing with the Landmines

Transplantation:Dealing with Landmines: 

Transplantation: Dealing with Landmines Shamkant Mulgaonkar MD Chief Transplant Division Saint Barnabas Health Care System New Jersey

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Death Death Death Death Death Death Death Death

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Nancy 28 year Old Dialysis nurse Type I Diabetes age 5 High BP, Proteinuria age 18 Age: 23, Creatinine 3.5 Creatinine Clearance 25 Healthy Parents 50’s 3 Healthy Siblings Age: 26, Develops Retinopathy Starts PD Peritonitis Hemodialysis.. Access problems

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Age: 27, Develops Dyspnea CHF Toe gangrene Age 28, Referred for Transplant Issues upon arrival Abnormal NST Abnormal ECHO Low EF Abnormal Carotids Abnormal PV studies Age 29, Needs CABG Carotid Bypass Stent both femorals Died at age 29 Death

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Team approach to serious problems Cardiac testing Vascular w/u Immediate transplant Referral to transplant Kidney or SPK Explore Living donors Dialysis preparation Diagnosis Treatment, tight BS+BP control ACEI ARB Pancreas or islet cell transplant Treatment of newly diagnosed DM Tight BS control Nancy 28 year Old Dialysis nurse Type I Diabetes age 5 High BP, Proteinuria age 18 Age: 23, Creatinine 3.5 Creatinine Clearance 25 Healthy Parents 50’s 3 Healthy Siblings Age: 26, Develops Retinopathy Starts PD..Peritonitis Hemodialysis.. Access problems

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Died at age 29 Vasculopathy Needs aggressive w/u Arrives alone, blind in a wheelchair Support, many problems Advanced cardiovascular Ineligible ! Age: 27, Develops Dyspnea CHF Toe gangrene Age 28, Referred for Transplant Issues upon arrival Abnormal NST Abnormal ECHO Low EF Abnormal Carotids Abnormal PV studies Age 29, Needs CABG Carotid Bypass Stent both femorals Death

What have we learned ?: 

What have we learned ? Reduce progression to ESRD : 10 years Surveillance cardiovascular : 10 years Early referral to transplant Prepare for dialysis Adequate dialysis Avoid cardiac and infection problems Early transplant with the best kidney : 20 years Early SPK or PAK transplant : 10 years Projected life expectancy: 65 years

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Jack 54 year old Truck driver African American ESRD unknown cause Permacath Hemodialysis Noncompliant from Day 1 5 foot 11 inches 312 lbs 1 ppd smoker Access clotted 4 times Transfused 4 units PC Unemployed Lost insurance

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Remains on dialysis 5 years Family ? No car Uncontrolled BP Dietary noncompliance 8 lb weight gain bet HD Referred to transplant center Leg Graft 59 year old, High PRA No work up in 5 years 2 brothers healthy 1 daughter All in Alabama

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W/u Renal tumor Hypernephroma Abnormal NST stent COPD Uncontrolled BP Dietary noncompliance 8 lb weight gain bet HD Continues to smoke Listed after w/u, insurance and counseling High PRA 90 % + crossmatch family no LD Died of MI at age 60 Death

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Jack 54 year old Truck driver African American ESRD unknown cause Permacath Hemodialysis Noncompliant from Day 1 5 foot 11 inches 312 lbs 1 ppd smoker Access clotted 4 times Transfused 4 units PC Unemployed Lost insurance Proper assessment of vascular access Coagulation studies Psychosocial issues Assist with insurance Approach to Obesity Smoking cessation Referral to transplant Creation of AV access Recurrent Nephropathy

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Remains on dialysis 5 years Family ? No car Uncontrolled BP Dietary noncompliance 8 lb weight gain bet HD Referred to transplant center Leg Graft 59 year old, High PRA No work up in 5 years 2 brothers healthy 1 daughter All in Alabama Willing donors Now an emergency !! Highly sensitized ? Medical problems of ESRD, Smoking, obesity Role of MD/RN/Dietitian Compliance Lost wait time for transplant Where is the family? Importance of transportation

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W/u Renal tumor Hypernephroma Abnormal NST stent COPD Uncontrolled BP Dietary noncompliance 8 lb weight gain bet HD Continues to smoke Listed after w/u, insurance and counseling High PRA 90 % + crossmatch family no LD Died of MI at age 60 May never get a transplant PERFECT PATIENT !!! Cancer and transplantation Stent or CABG and wait time Sleep apnea, COPD Death

What have we learned?: 

What have we learned? Diagnose cause of ESRD : Recurrence Surveillance cardiovascular Early referral to transplant W/U Hypercoagulation Aggressive counseling: Dialysis Compliance, Diet, Meds, Cigarette Smoking, Pot Involve family members Assist in insurance matters Adequate dialysis Avoid anemia and transfusions Early transplant with the best kidney

Who is responsible for the death of Nancy and Jack?: 

Who is responsible for the death of Nancy and Jack? Patient and family Society Internist Endocrinologist Nephrologist Predialysis educator Dialysis nurse Dialysis social worker Transplant center

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Projected Years of Life from WL for WL Dialysis vs. Transplant Patients by Age Group Projected Years of Life 40 0 20-39 40-59 60-74 Wait List Dialysis Transplant Age Group 20 00079

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Projected Years of Life from WL for WL Dialysis vs. Transplant by DM (Age 40-59) DM Non-DM Projected Years of Life 40 0 20 Wait List Dialysis Transplant 00082

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63 % 29 % 58 % 78 % Graft survival in of 2,405 recipients of paired kidneys months post-transplant 0-6 months on dialysis >24 months on dialysis

Take Charge : 

Take Charge Think Death Think Early intervention Think Team approach Think Family Think Insurance Think Compliance Assume responsibility Think Death

Conclusions: 

Conclusions Renal transplantation is associated with a survival advantage This survival advantage over maintenance dialysis is maintained even when marginal kidneys are used for transplantation Waiting time on dialysis is associated with an increased risk for graft loss and patient death after renal transplantation

Incompatible Renal TransplantationorHigh Risk Transplantation: 

Incompatible Renal Transplantation or High Risk Transplantation

High Risk Renal Transplantation: 

High Risk Renal Transplantation Demographic : Child or age>60, African American Medical : Diabetic, Uncontrolled BP, cardiac problems, High BMI, + Viral infections, Sickle cell disease Surgical : Major abdominal surgery, access, vascular Psychosocial : Noncompliance, Lack of family support, Lack of insurance, alcohol/substance abuse Allograft : Imported, DCD or ECD Immunologic :High PRA, Sensitizing events, Incompatible Blood group

Incompatible Renal Transplantation: 

ABO Blood Group Incompatible HLA (Cross Match) Incompatible Incompatible Renal Transplantation

Blood Group: ABO: 

Blood Group: ABO O : Universal donor can receive only O or A2 A : Can receive from A or O B: Can receive from B or O AB : Universal recipient, Can receive from A,B,AB or O

Facts: 

Facts It is possible that blood group antigens may be shared by some bacteria, leaves and seeds of plants. Infants have low levels and older patients have higher levels due to this exposure.

Jill: 

Jill 25 year old type I diabetes age 4. Creatinine 5 ( Creatinine clearance 10). Blood group O. Parents : Medical problems. 1 Brother willing donor : Blood group A. No other donors.

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Plasma exchange IVIG

OutcomesShort termLong term: 

Outcomes Short term Long term

Post transplant: 

Post transplant Nonadherance

Introduction: 

Introduction “Drugs don’t work in patients who don’t take them” -C. Everett Koop, M.D. Non-adherence to transplant medications Important and leading cause of transplant failure Gaston RS, Hudson SL, Ward M, Jones P, Macon R. Late renal allograft loss: noncompliance masquerading as chronic rejection. Transplantation Proceedings. 1999;31(4, Supplement 1):21S-23S. Precedes over 1/3 of transplant failures Butler JA, Roderick P, Mullee M, Mason JC, Peveler RC. Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. Transplantation. 2004;77(5):769-776.

Non-adherence in general nephrology: 

Non-adherence in general nephrology Hemodialysis Newmann JM, Litchfield WE. Adequacy of dialysis: the patient's role and patient concerns. Semin Nephrol. 2005;25(2):112-9. Hecking E, Bragg-Gresham JL, Rayner HC, et al. Haemodialysis prescription, adherence and nutritional indicators in five European countries: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant. 2004;19(1):100-7. Peritoneal dialysis Bernardini J, Piraino B. Compliance in CAPD and CCPD patients as measured by supply inventories during home visits. Am J Kidney Dis. 1998;31(1):101-7.

Case: 

Case 39 year old Black female ESRD due to HTN s/p deceased donor renal transplant 5/2002 Creatinine 0.8 in 2004 Recent serum Cr in 2.5-3.0 range Transplant biopsy spring 2005 Moderate chronic allograft nephropathy Immunosuppressive regimen Prednisone Cyclosporine (Neoral) Mycophenolate mofetil (Cellcept)

Case (continued): 

Case (continued) On emergency visit to transplant clinic, Complained of SOB and DOE for past week Ran out of metoprolol several weeks before Serum Cr 8.5 Admitted to Saint Barnabas Medical Center Repeat transplant biopsy Severe chronic allograft nephropathy Acute cellular rejection, grade 1B Treated with high-dose corticosteroids Upon further questioning, patient admitted Not taking prednisone for past several months Not taking mycophenolate mofetil for past 3 weeks Awaiting mail delivery of prescriptions

Case (continued): 

Case (continued) Hospital course Started on hemodialysis for uremic symptoms Immunosuppressive medications changed Cyclosporine replaced with tacrolimus When dialysis held, transplant failed to show any function Patient returned to maintenance dialysis

Profiles of non-adherent patients: 

Profiles of non-adherent patients Greenstein S, Siegal B. Compliance and noncompliance in patients with a functioning renal transplant: a multicenter study. Transplantation. 1998;66(12):1718-26. “Accidental” non-compliers Disorganized Medication ingestion is not a priority “Invulnerables” Believe that they do not need to take their immunosuppressive medications regularly “Decisive” noncompliers Independent rationales for non-adherence

Reasons for non-adherence:Medication costs: 

Reasons for non-adherence: Medication costs Anti-rejection medications with 20% co-pay: $260.64 Other transplant medications: $1101.41 Having a working transplant kidney and staying off dialysis: Priceless

Reasons for non-adherence:Complexity of treatment regimen: 

Reasons for non-adherence: Complexity of treatment regimen Increased dosing frequency Leads to decreased adherence Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296-310.

Reasons for non-adherence:Psychosocial factors: 

Reasons for non-adherence: Psychosocial factors Depression Kiley DJ, Lam CS, Pollak R. A study of treatment compliance following kidney transplantation. Transplantation. 1993;55:51-6. Stress Frazier PA, Davis-Ali SH, Dahl KE. Correlates of noncompliance among renal transplant recipients. Clin Transplant. 1994;8:550-7. Health locus of control Raiz LR, Kilty KM, Henry ML, Ferguson RM. Medication compliance following renal transplantation. Transplantation. 1999;68:51-5. Race Schweizer RT, Rovelli M, Palmeri D, Vossler E, Hull D, Bartus S. Noncompliance in organ transplant recipients. Transplantation. 1990;49:374-7.

Reasons for non-adherence: Side effects of medicines: 

Reasons for non-adherence: Side effects of medicines Medication side effects are under-recognized by transplant professionals Peters TG, Spinola KN, West JC, Aeder MI, Danovitch GM, Klintmalm GB, et al. Differences in patient and transplant professional perceptions of immunosuppression-induced cosmetic side effects. Transplantation. 2004;78:537-43. Cosmetic changes Important cause of non-adherence among adolescents and young adults

Prevalence of non-adherence: 

22% of transplant recipients were non-adherent Median of 36.4% of graft losses are associated with prior non-adherence Probably underestimates the actual incidence Prevalence of non-adherence

Interventions to increase adherence: 

Interventions to increase adherence Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487-97. Patient education Improved dosing schedules Improved communication between physicians and patients

Why there will not be a Steroid booth at Meetings ?: 

Why there will not be a Steroid booth at Meetings ? Weight gain Mood changes Cataract Osteoporosis Avascular necrosis Hypertension Diabetes mellitus Depression Peptic ulcer Infections Skin friability Abdominal strae Hyperlipidemia Cosmetic changes: moon face, hirsutism, acne

SBHCS Protocol : Immunosuppression: 

SBHCS Protocol : Immunosuppression Thymoglobulin 6 mg/kg over 3-4 days starting intra op Solumedrol 500 mg pre-op, then 250 mg bid post-op day 1, 125 mg bid post op day 2 and 60 mg bid post op day 3 Tacrolimus:Trough levels 10 for 90 days, 8-10 until 365 days,5-8 after 365 days Mycophenolate Mofetil 1 gram bid In Sirolimus arm : Levels 10 for 90 days, 5-8 until 365 days and 5 thereafter. Suspected ACR: Biopsy and treatment with Thymoglobulin, no steroids Prophylaxis: Bactrim DS, Mycelex, Valcyte

Results: 

Results 120 patients March 2003-March 2006 Patient survival 98% Kidney survival 96% BP controlled with less meds Decreased incidence of NOD No bone fractures Cosmesis excellent No psych problems Improved adherence

Graft Loss: 

Graft Loss Acute rejection Chronic allograft nephropathy Impact of return to dialysis

Treatment of Acute Rejection: 

Treatment of Acute Rejection

Chronic RejectionChronic Allograft Nephropathy[CAN]: 

Chronic Rejection Chronic Allograft Nephropathy [CAN] One of the most common causes of CKD 25 % Patients waiting for TSP have chronic allograft failure. 20% Kidneys go to patients who have failed 1 or more transplants.

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HLA Matching Acute rejection Non adherence Infections Hypertension Recurrent disease