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Transplantation: Dealing with Landmines. Shamkant Mulgaonkar MD Chief Transplant Division Saint Barnabas Health Care System New Jersey. Death. Death. Death. Death. Death. Death. Death. Death. Nancy 28 year Old Dialysis nurse Type I Diabetes age 5. High BP, Proteinuria age 18.
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Transplantation:Dealing with Landmines Shamkant Mulgaonkar MD Chief Transplant Division Saint Barnabas Health Care System New Jersey
Death Death Death Death Death Death Death Death
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
Age: 27, Develops Dyspnea CHF Toe gangrene Death Age 28, Referred for Transplant Issues upon arrival Died at age 29 Abnormal NST Abnormal ECHO Low EF Abnormal Carotids Abnormal PV studies Age 29, Needs CABG Carotid Bypass Stent both femorals
Nancy 28 year Old Dialysis nurse Type I Diabetes age 5 Treatment of newly diagnosed DM Tight BS control High BP, Proteinuria age 18 Diagnosis Treatment, tight BS+BP control ACEI ARB Pancreas or islet cell transplant Age: 23, Creatinine 3.5 Creatinine Clearance 25 Healthy Parents 50’s 3 Healthy Siblings Referral to transplant Kidney or SPK Explore Living donors Dialysis preparation Age: 26, Develops Retinopathy Starts PD..Peritonitis Hemodialysis.. Access problems Team approach to serious problems Cardiac testing Vascular w/u Immediate transplant
Age: 27, Develops Dyspnea CHF Toe gangrene Vasculopathy Needs aggressive w/u Age 28, Referred for Transplant Issues upon arrival Arrives alone, blind in a wheelchair Support, many problems Abnormal NST Abnormal ECHO Low EF Abnormal Carotids Abnormal PV studies Advanced cardiovascular Ineligible ! Death Age 29, Needs CABG Carotid Bypass Stent both femorals Died at age 29
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
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
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
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 Death Died of MI at age 60
Jack 54 year old Truck driver African American ESRD unknown cause Recurrent Nephropathy Permacath Hemodialysis Noncompliant from Day 1 Referral to transplant Creation of AV access 5 foot 11 inches 312 lbs 1 ppd smoker Approach to Obesity Smoking cessation Access clotted 4 times Transfused 4 units PC Unemployed Lost insurance Proper assessment of vascular access Coagulation studies Psychosocial issues Assist with insurance
Remains on dialysis 5 years Family ? No car Lost wait time for transplant Where is the family? Importance of transportation Uncontrolled BP Dietary noncompliance 8 lb weight gain bet HD Role of MD/RN/Dietitian Compliance Referred to transplant center Leg Graft 59 year old, High PRA No work up in 5 years Now an emergency !! Highly sensitized ? Medical problems of ESRD, Smoking, obesity 2 brothers healthy 1 daughter All in Alabama Willing donors
W/u Renal tumor Hypernephroma Abnormal NST stent COPD Cancer and transplantation Stent or CABG and wait time Sleep apnea, COPD Uncontrolled BP Dietary noncompliance 8 lb weight gain bet HD Continues to smoke PERFECT PATIENT !!! Listed after w/u, insurance and counseling High PRA 90 % + crossmatch family no LD May never get a transplant Death Died of MI at age 60
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? • Patient and family • Society • Internist • Endocrinologist • Nephrologist • Predialysis educator • Dialysis nurse • Dialysis social worker • Transplant center
Projected Years of Life from WL for WL Dialysis vs. Transplant Patients by Age Group Projected Years of Life 40 Wait List Dialysis Transplant 20 0 20-39 40-59 60-74 Age Group 00079
Projected Years of Life from WL for WL Dialysis vs. Transplant by DM (Age 40-59) 40 Projected Years of Life Wait List Dialysis Transplant 20 0 Non-DM DM 00082
Graft survival in of 2,405 recipients of paired kidneys 78 % 0-6 months on dialysis >24 months on dialysis 63 % 58 % 29 % months post-transplant
Take Charge • Think Death • Think Early intervention • Think Team approach • Think Family • Think Insurance • Think Compliance • Assume responsibility • Think Death
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
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
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 • 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 • 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. Should or Can we do this transplant?
No BG compatible donors ABOI Titers Plasma exchange IVIG Recheck Titers Prednisone Prograf Cellcept Retuximab Thymoglobulin Transplant PP IVIG
Post transplant Nonadherance
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 • 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 • 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) • 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) • 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 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: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: 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
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
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 Why there will not be a Steroid booth at Meetings ?
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 • 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 • Acute rejection • Chronic allograft nephropathy • Impact of return to dialysis
Chronic RejectionChronic 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.
Can We Prevent Chronic Allograft Nephropathy? • HLA Matching • Acute rejection • Non adherence • Infections • Hypertension • Recurrent disease