Evaluation of Potential Kidney Transplant Recipients Donald E. Hricik MD Professor of Medicine and Chief, Division of Nephrology and Hypertension University Hospitals Case Medical Center Conflict of Interest Disclosure Donald E. Hricik, MD Employer: University Hospitals Case Medical Center Research Funding: Astellas Honoraria: Genentech, Novartis Overview Benefits and risks of kidney transplantation Indications and contraindications Special circumstances Recurrent kidney diseases Hepatitis/HIV Pre-existing malignancy Psychosocial issues High risk or known cardiovascular disease Evaluation Laboratory studies Imaging studies Principles of tissue typing and crossmatching Informed consent for Expanded Criteria Donor kidneys Projected Years of Life in Patients with ESRD Age and Diabetes Status Wait-Listed Transplanted 20-39 yr, no DM 20 31 20-39 yr, DM 8 25 40-59 yr, no DM 12 19 40-59 yr, DM 8 22 60-74 yr, no DM 7 12 60-74 yr, DM 5 8 Wolfe RA, et al. NEJM 1999; 341: 1725 1
Survival Benefit of Transplantation vs. Waiting on Dialysis Cost Comparison: Maintenance Dialysis vs Transplantation Wolfe RA et al, N Engl J Med 1999; 341:1725 Per Patient Per Year Costs Transplant Versus Dialysis Patients Waiting for A Kidney Transplant 2006 USRDS Annual Report 2005 USRDS Annual Report 2
Absolute Contraindications to Transplantation Active infection (HIV no longer an absolute contraindication) Active malignancy Active drug use, alcoholism, or psychosis High potential for noncompliance Anatomy that makes transplantation technically impossible Indications for Transplantation End stage renal disease (stage V CKD), or CKD with GFR < 20 ml/min*, or Significant symptoms of uremia, or Acid-base or electrolyte abnormalities that are unresponsive to medical interventions *required for waitlist activation Allograft Survival: Impact of Donor Source and Waiting Time Relative Contraindications to Kidney Transplantation Cardiovascular disease Coronary, peripheral, cerebrovascular Pulmonary disease Gastrointestinal or hepatic disease Active smoking High (BMI > 35,? 40,? higher) Systemic amyloidosis Psychosocial/financial situation resulting in inability to achieve adequate posttransplant care Advanced age 3
Recurrent Diseases SLE quiescent on < 10 mg prednisone for 6 months (?clinical vs serologic quiescence) Anti-GBM disease quiescent with undetectable ant- GBM antibody Vasculitides quiescent for 6 months (controversy about ANCA titers) FSGS 20-30% recurrence rate but much higher with history of recurrence in first allograft; 30% graft loss HUS higher recurrence rate in nondiarrheal form MPGN Recurrences of 50-100% in type 2 with high rate of graft loss Recurrent Diseases, continued Primary oxalosis high rate of graft loss from oxalate deposition. A staged or combined liverkidney transplant preferred for Type 1 IgA nephropathy recurrence rate 20-50%; low rates of graft loss Membranous recurrence rate 10%; rare cause of graft loss Diabetic nephropathy 100% recurrence ; rare cause of graft loss Prevalence of Hepatitis in Transplant Candidates Pre-transplant Evaluation and Management of Patients with Hepatitis B or C Hepatology consult Screening for HCC (ultrasound) Liver biopsy consider combined liver transplantation for severe disease Encourage pre-transplant therapy; IFN increases risk of rejection post-transplant Consider hepatitis C positive donor for hepatitis C positive recipients 2004 USRDS Annual Report 4
Outcomes of Patients with Hepatitis B or C HIV and Kidney Transplantation Relatively high rates of acute rejection Strong interaction between HAART and immunosuppressants metabolized by CYP450 (CNIs, TOR Inhibitors) Long-term outcomes remarkably good (patients with hepatitis C do less well) NIH consortium performing ongoing studies in kidney and liver transplantation 2004 USRDS Annual Report Outcomes of Patients with HIV 2004 USRDS Annual Report Waiting Times for Preexisting Malignancies Most malignancies require at least a 2-year period of remission At least 5 years required for: Colorectal Dukes B1 or higher Advanced Breast cancer Invasive Cervical cancer Renal Cell Carcinoma > 5 cm or < 5 cm with invasion In situ lesions no wait Non-melanoma skin ca no wait Multiple myeloma contraindicated unless with stem cell transplant MGUS no wait 5
Special Procedures for Special Patients Patients with a history of drug or alcohol abuse may require random drug screening before proceeding further Patients with a history of noncompliance may be asked to comply with a compliance contract before proceeding further Cardiac Screening and Evaluation Men > 45 y.o.; women > 50 y.o. All diabetics Patients with history of coronary disease Patients with symptoms of coronary disease Patients with EKG evidence of ischemia Evaluation: Cardiac echo Stress testing with perfusion studies Cardiology consultation and catheterization for patients with a positive stress test Recipient Evaluation Laboratory Evaluation Patient education History and physical examination Social history Family history of medical/kidney disease Medications/allergies History of sensitizing events (blood transfusions, pregnancies prior transplants Colonoscopy > 50 y.o. or > 40 y.o. with family history Pap and pelvic examinations Chemistry BUN, Cr, electrolytes, LFTs, lipid panel Estimated GFR if predialysis Hematology ABO blood type HLA typing Panel reactive antibodies CBC, INR & PTT, Hypercoagulability panel if history of thromboses Serology Hepatitis B (core and surface Ab, surface Ag) CMV, EBV and Varicella antibody titers HIV Hepatitis C Ab screen (PCR to confirm) RPR or VDRL Urinalysis/Urine culture Urine drug screen PPD 6
Optional Laboratory Evaluation Urine cytology in patients exposed to cyclophosphamide, or if diagnosed with analgesic nephropathy or Chinese herbal nephropathy PSA men > 50 y.o. or > 45 y.o. if family history Imaging Studies Chest x-ray Mammograms women > 40 y.o. or > 35 y.o. if family history Imaging of aorto-iliac arterial tree (diabetics, age > 50 y.o., diminished pulses, history of PVD) Duplex scanning High resolution CT Optional Ancillary or Supplemental Evaluations Recipient Vaccinations Dental evaluation Social service evaluation Dietary evaluation Ophthalmologic evaluation Financial evaluation Psychiatric evaluation VCUG Peripheral vascular studies Upper endoscopy Pulmonary function tests Vaccinate pre-transplant! Hepatitis B Pneumovax if > 5 years since last dose Varicella if titers negative Tetanus and diptheria booster if > 10 years since last dose? Hepatitis A? HPV? Meningococcus? Hemophilus 7
Principles of Tissue Typing and Crossmatching Accurate tissue typing and crossmatching are essential for optimal transplant outcomes ABO Blood Group Typing ABO blood group must be compatible A2 into O and A2 and A2B into B are compatible combinations MHC GENE EXPRESSION The Pretransplant Crossmatch Standard complement dependent crossmatch (CDC, NIH technique) Anti-human globulin enhanced crossmatch Flow cytometry crossmatch (B cell crossmatching) Limited tissue distribution Found on all nucleated cells 8
Antiglobulin-Enhanced Technique More sensitive Can detect noncomplement binding antibodies Can detect antibodies present in small amounts Patel and Terasaki, NEJM 280:735, 1969 9
Role of Anti-Human Globulin Enhanced Crossmatch on Two Year Kidney Transplant Outcomes All patients had negative NIH standard crossmatches. Deceased Donor Recipients 1st Transplants Negative NIH Standard Crossmatch All Patients 81% (N = 166) Re-Transplants 64% (N = 70) Anti-Human Globulin Crossmatch Negative Two Year Graft Survival 82% (N = 151) 77% (N = 48) Positive 67% (N = 15) 36% (N = 22) P-Value < 0.01 < 0.01 Kerman et.al. Transplantation. 51:316, 1991 Flow Cytometry Crossmatch Most sensitive of all the crossmatches In some labs, not used if the less sensitive crossmatches are positive Can be used if the don or lymphocytes are dead 10
Purpose of Determining if a Patient Is Sensitized Defines high risk status triggers different management Simplifies work in the tissue typing laboratory Determines organ allocation Predicts when a patient might be transplanted Highly sensitized patients wait longer Highly sensitized patients have inferior graft survival rates Expanded Criteria Donor (ECD) 3-Year Graft Survival by Donor Type Deceased donor 60 years of age Deceased donor 50 to 59 years of age with at least two of the following: History of hypertension Terminal SCr >1.5 mg/dl Death from cerebral vascular accident Associated with 70% higher risk of graft failure compared with non-ecd transplants Merion RM et al. JAMA. 2005;294:2726-2733. Port FK et al. Transplantation. 2002;74:1281. OPTN/SRTR 2005 Annual Report www.ustransplant.org. OPTN/SRTR 2005 Annual Report www.ustransplant.org. 11
Survival Benefit of Kidney Transplantation ECD Rules Inform all potential recipients Informed consent required Who should get an ECD kidney?? Ojo et al. J Am Soc Nephrol 2001; 12: 589. 12