Long-Term Surveillance of the Kidney Transplant Patient. Introduction. Chronic Allograft Nephropathy. UCSF Post Kidney Transplant Clinic

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1 UCSF Post Kidney Transplant Clinic Long-Term Surveillance of the Kidney Transplant Patient Allison Webber, MD Melanie Macaraig, NP University of California, San Francisco Multidisciplinary team: -5 Transplant Nephrologists -2 NPs -LVN -Social Workers -Dietician Short-term clinic: post-op < 90 days Long-term clinic: post-op > 90 days - Kaiser Nephrology Specialty Department Patients return to local provider after 3 months AND continue visits at UCSF. Approx 3500 post transplant patients followed at UCSF Introduction Despite significant improvement in acute rejection rates, long term renal allograft survival has remained unchanged since The major causes of late allograft loss are chronic allograft nephropathy and death with a functioning graft Chronic Allograft Nephropathy Two main types: Immunologic injury (true chronic rejection) Mixed, nonimmunologic causes (due to either acute or chronic injury) Meier-Kriesche, HU. AJT 2004 March;4(3). 1

2 Causes of death with function, Late Issues-Outline USRDS 2009 Patients age 18 & older, Chronic allograft dysfunction and deterioration 2. Metabolic syndromes a. DM b. HTN c. Hyperlipidemia d. Bone disease e. Chronic anemia 3. Infections 4. Malignancy Chronic Allograft Dysfunction-How can you help? Adherence Drug Monitoring Medication Adherence 15% to 55% of patients exhibit nonadherence at one time or another Rate of non-adherence to immunosuppression medication is highest among kidney tx pts Major cause of graft failure Nonadherent patients have 4 to 5 times greater risk of graft loss Graft loss can occur as early as 3 to 6 months posttransplant 1. Greenstein S, et al. Transplantation. 1998;66: Dehhaerynck K, et al. Transplant International. 2005; 18: Nevins TE, et al. Kidney Int. 2001;60: Dew MA, et al. Transplantation, 2007; 83:

3 Medication Adherence Recognizing these factors can guide the health care team with behavioral and educational interventions to promote compliance and decrease risk of nonadherence related rejection. Prendergast, MB, Gaston, RS. CJASN. 2010; 5: Provide lifelong education, individualize post transplant care, evaluate treatment burden, take into account patient belief and social factors, multidisciplinary approach. Drug Monitoring Measure trough levels of calcineurin inhibitors (cyclosporine or tacrolimus) every 1-3 months after 1 year Drug Interactions Increases Cyclosporine/Tacrolimus levels Diltiazem/Nicardipine/Verapamil Fluconazole/Itraconazole/Ketoconazole Clarithromycin/Erythromycin Decreases Cyclosporine/Tacrolimus levels Rifabutin/Rifampin Carbamazepime/Phenobarbital/Phenytoin St. John s Wort 3

4 Causes of death with function, Cardiovascular Events The annual rate of fatal or nonfatal CVD events in kidney transplant recipients is 3.5-5%, 50-fold higher than in the general population. USRDS 2009 Patients age 18 & older, USRDS 2007 Annual data report Late Issues-Outline 1. Chronic allograft dysfunction and deterioration 2. Metabolic syndromes a. DM b. HTN c. Hyperlipidemia d. Bone disease e. Chronic anemia 3. Infections 4. Malignancy Traditional Risk Factors for CVD High blood cholesterol and lipoproteins High blood pressure (>140/90 mm Hg) Diabetes mellitus Metabolic syndrome Tobacco use (chewing, smoking, or environmental exposure) Physical inactivity Obesity/overweight (BMI >25 kg/m 2 ) American Heart Association. Heart Disease and Stroke Statistics 2005 Update

5 Hyperlipidemia Common in patients with chronic kidney disease and even more so in kidney transplant recipients Characterized by a significant increase in one or more of the following: Total cholesterol (>200 mg/dl) LDL-C (>130 mg/dl) Triglycerides (>150 mg/dl) VLDL-C (>35 mg/dl) Lipoprotein (a) Target Serum Lipid Levels for Kidney Transplant Recipients Total Cholesterol <200 mg/dl LDL-C HDL-C Triglycerides Kasiske B, et al. Am J Transplant. 2004;4(suppl 7): <100 mg/dl >40 mg/dl <150 mg/dl Hypertension Hypertension is found in 90% of kidney transplant recipients Common causes of transplant-associated hypertension include: Native kidney disease or preexisting comorbid conditions Immunosuppressive agents, such as corticosteroids and CNIs The allograft itself (ie, chronic dysfunction/rejection) Renal artery stenosis in either the native kidney or allograft Schwenger V, et al. Ann Transplant. 2001;6: Target Blood Pressure for Kidney Transplant Recipients Goal blood pressure: <130/80 mm Hg KDOQI 2004/ KDIGO Clinical Practice Guidelines AJT

6 Incidence of NODM in Nondiabetic Kidney Transplant Recipients Survival Free of Post-transplant Diabetes defined on the basis of Medicare Claims 25 Patients, % year 3 years 5 years 10 years 15 years Cosio FG, et al. Kidney Int. 2001;59: Time Posttransplant 3 months (9.1%) 12 months (16%) 36 months (24%) Kasiske B, et al Am J Transplantation 2003; 3: Screening-Diabetes The American Society of Transplantation recommends posttransplant screening Weekly for months 1 to 3 Every other week for months 4 to 6 Monthly for months 6 to 12 At least yearly after 12 months Management of Diabetes After Transplantation Complicated by the competing effects of changing renal function and diabetogenic immunosuppressants As renal function improves posttransplantation, insulin requirements increase Goals for adequate glycemic control: Fasting blood glucose 90 to 130 mg/dl A1c <7.0% Kasiske BL, et al. J Am Soc Nephrol. 2000;11:S1-S86. The American Association of Clinical Endocrinologists Medical Guidelines for the Management of Diabetes Mellitus: The AACE System of Intensive Diabetes Self-Management 2002 Update. Endocrine Practice. 2002;8(suppl):S40-S82. 6

7 Late Issues-Outline Causes of death with function, Chronic allograft dysfunction and deterioration 2. Metabolic syndromes a. DM b. HTN c. Hyperlipidemia d. Bone disease e. Chronic anemia 3. Infections 4. Malignancy USRDS 2009 Patients age 18 & older, Timing of Post-Transplant Infections Zero - 1 month Wound infections Line sepsis UTIs Pneumonia Herpesvirus Oral candidiasis Brennan DC, Bohl D. In: Clinical Nephrology, Dialysis and Transplantation. Timing of Post-Transplant Infections Two -6 months BKV CMV P carinii A fumigatus Candida species Nocardia species T gondii L monocytogenes Hepatitis B and C Histoplasmosis Coccidioidomycosis Brennan DC, Bohl D. In: Clinical Nephrology, Dialysis and Transplantation. 7

8 Timing of Post-Transplant Infections Late Issues-Outline Beyond 6 months Community infections CMV retinitis Cryptococcus Polyoma virus M. Tuberculosis Atypical mycobacterium Brennan DC, Bohl D. In: Clinical Nephrology, Dialysis and Transplantation. 1. Chronic allograft dysfunction and deterioration 2. Metabolic syndromes a. DM b. HTN c. Hyperlipidemia d. Bone disease e. Chronic anemia 3. Infections 4. Malignancy Screening for Malignancy Skin Cancer Most prevalent malignant condition in solid-organ transplant recipients. More aggressive than in the general population Recurrence and metastases are common Yearly skin examinations are recommended for all kidney transplant recipients Post-Transplant Lymphoproliferative Disorder (PTLD) Overall incidence is 1%, times higher than in the general population Usually B cell lymphomas Clinically: Lymphadenopathy, fevers, weight loss, sometimes CNS Degree of overall immunosuppression EBV serostatus of the recipient 8

9 Screening For Malignancy Cervical Cancer Female kidney transplant recipients have a 3-to 16-fold greater risk for developing cervical cancer Annual pap smears recommended Colorectal Cancer 2-to 4-fold increase in risk for colon cancer after the first 10 years after kidney transplantation Follow screening recommendations from American Cancer Society Prostate Cancer Annual PSAs and DRE recommended Breast Cancer No greater incidence than the general population Follow screening recommendations from American Cancer Society Summary- How can you help improve long term allograft function? Ensure Patient Adherence with Immunosuppressive Drug Regimens Monitor drug levels at least every 3 months after 1 year-especially after changes in medical regimen Screen and treat the metabolic syndrome including aggressive treatment of hypertension, diabetes, and hyperlipidemia. Screen for infections and malignancies. Future Directions Immune Monitoring techniques Donor specific antibody monitoring Genomics/Proteomics-urine/blood Immunkow (Cylex) Management (Protocol) Biopsies at 6 months UCSF Post Kidney Transplant Clinic Contact info: Connie Frank Transplant Center 400 Parnassus Ave, Ste A701 San Francisco, CA Tel: Fax: