*2.2.1. Biomarkers for cardiac risk assessment*

All prospective transplant candidates

Figure 1. Suggested algorithm for pretransplant cardiac evaluation

Thorough history and physical exam to identify active cardiac conditions

Active cardiac condition(s) present?

Yes No

• Diabetes

• Age > 60 • Smoking • Hypertension • Dyslipidemia

No

1Unstable coronary syndromes: unstable angina, severe angina, recent myocardial infarction

2Myocardial perfusion study or dobutamine stress echocardiogram (center specific).

Coronary angiogram

Management per AHA/ACC guidelines; Cardiology referral

1Unstable coronary syndromes: unstable angina, severe angina, recent myocardial infarction 2Myocardial perfusion study or dobutamine stress echocardiogram (center specific).

**Figure 1.** Suggested algorithm for pretransplant cardiac evaluation

Abnormal

Non-invasive stress test2 if > 3 risk factors:

Normal stress test

Normal

Yes

List/Transplant

• Prior cardiovascular disease • Dialysis duration > 12 months • Left ventricular hypertrophy (LVH)

• Unstable coronary syndromes1 • Decompensated heart failure • Significant arrhythmias • Severe valvular disease

Delay or cancel transplant

10 Current Issues and Future Direction in Kidney Transplantation

In recent years, cardiac troponin T (cTnT) has been suggested to provide prognostic informa‐ tion in the cardiac evaluation of patients with ESKD. Independent investigators have demon‐ strated an association between increased levels of cardiac toponin T isoforms and all-cause and cardiac death risk in asymptomatic patients with ESKD (Lentine et al., 2009, Khan et al., 2005). In a study consisting of 644 wait-listed renal transplant candidates, Hickson *et al.* demonstrated that increasing cTnT levels were associated with progressively reduced survival independent of low serum albumin and history of stroke. The survival of patients with cTnT levels between 0.01 and 0.03 ng/mL did not differ from that of patients with levels < 0.01 ng/mL. In contrast, cTnT levels between 0.03 and 0.09 ng/mL were associated with significantly increased mortality (hazard ratio, HR=3.01, p=0.040). Notably, mortality was further increased in patients with cTnT levels >0.1 ng/mL (HR=4.085, p=0.009) whereas in patients with normal cTnT, excellent survival was achieved independent of other risk factors (Hickson et al., 2008). The 2012 AHA/ACA guidelines support the use of cTnT level at the time of evaluation for kidney transplantation as an additional prognostic marker (Class IIb; Level of Evidence B) (Lentine et al., 2012). However, the routine use of cTnT as adjunctive tools in cardiac risk assessment in renal transplant candidates remains to be studied.

#### **2.3. Nonischemic cardiomyopathy**

Patients with CKD frequently suffer from nonischemic cardiac abnormalities including left ventricular hypertrophy (LVH), left ventricular dilatation, left ventricular systolic and/or diastolic dysfunction. Renal transplantation has variably been shown to improve left ventric‐ ular dysfunction and ameliorate LVH (Zolty et al., 2008). Hence, the presence of such abnor‐ malities does not necessarily preclude transplantation. Nonetheless, patients with an ejection fraction of 40% are considered moderate to high risk candidates and warrant a formal Cardiology consultation. An ejection fraction below 40% generally precludes transplantation. It is our practice to refer these patients to Cardiomyopathy Center for further diagnostic and therapeutic interventions. The presence of advanced irreversible cardiomyopathy is a contra‐ indication to solitary kidney transplantation and patients should be referred for possible combined kidney-heart transplantation.

#### **2.4. Peripheral vascular disease**

Patients with a history of transient ischemic attacks or cerebrovascular accidents should under‐ go carotid Doppler studies. Duplex ultrasonography may be considered in asymptomatic pa‐ tients with symptomatic peripheral arterial disease (PAD), CAD, or atherosclerotic aortic aneurysm (Class IIb). Patients without clinical evidence of atherosclerosis may also be screened if they have 2 or more risk factors including hypertension, hyperlipidemia, cigarette smoking, family history of atherosclerosis manifested before age 60 in a first-degree relative, or family history of ischemic stroke (Class IIb). It is also reasonable to screen asymptomatic patients with a carotid bruit (Class IIa). Lastly, asymptomatic patients with known or suspected carotid ar‐ tery disease are recommended to undergo duplex ultrasonography studies (Class I) (Lentine et al., 2012). Evidence of significant stenosis requires vascular surgery consultation. If necessary, carotid endarterectomy should be performed prior to transplantation and patients should be symptom free for at least six months prior to transplantation. For those with milder carotid dis‐ ease, neurology consultation and optimal medical management may be sufficient.

Infection with influenza A (H1N1) virus has emerged as an important cause of morbidity and mortality in the general and dialysis population worldwide. More importantly, infected patients on chronic dialysis treatment were found to have a 10-fold higher mortality rate compared to the general population (Marcelli et al., 2009). Recipients of solid organ transplants have also been suggested to be at risk for more severe disease (Kumar et al., 2010). In a multicenter cohort study consisting of 237 adult and pediatric solid organ transplant recipients with microbiological-confirmed influenza A H1N1 infection, 71% required hospitalization. Among 230 patients for whom data on complications were available, 32% had pneumonia, 16% were admitted to the intensive care units, and ten (4%) died.(Kumar et al., 2010) Hence, unless contraindicated, influenza A (H1N1) vaccine should be considered in all prospective

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13

Hepatitis B antigenemia does not preclude transplant candidacy. However, patients should be referred for a liver biopsy to assess the severity of liver disease because liver enzymes may be spuriously normal despite necroinflammatory changes on biopsy (Fabrizi et al., 2010). Transplant candidacy should be based on both liver histology and serologic evidence of HBV replication (i.e. HBV DNA and HBeAg positivity). In transplant candidates with active HBV replication, antiviral therapy should be initiated pretransplantation. The presence of histolog‐ ically mild liver disease does not preclude transplantation. However, patients should be forewarned that the introduction of immunosuppressive therapy in the posttransplant period can lead to progression of liver disease even in patients with histologically mild disease before transplantation. All patients with HBV should be placed on antiviral therapy after transplan‐ tation to prevent HBV reactivation and replication and progression of liver disease. Similar to HBV infection, liver biopsy is essential in the evaluation of transplant candidate with HCV because clinical and biochemical findings are unreliable indicators of the severity of liver disease in the dialysis population. The presence of minimal to mild chronic hepatitis (stages I and II) does not preclude transplantation. Pretransplantation antiviral treatment should be considered to prevent the progression of liver disease and protect the graft against HCVrelated glomerulonephritis (Fabrizi et al., 2010). It should be noted that there is currently no effective treatment for chronic hepatitis C in renal transplant recipients. Although treatment with interferon-α may result in clearance of HCV RNA in 25-50% of cases, rapid relapse following drug withdrawal is nearly universal. More importantly, interferon-α treatment has been shown to precipitate acute allograft rejection and graft loss and is currently not routinely recommended for renal transplant recipients with HCV infection. The use of interferon-α should be individualized at the discretion of the transplant nephrologist and hepatologist. Studies evaluating interferon-free regimens are currently underway (Yee et al., 2012). Hepatitis C positive transplant candidates should be given the option of receiving a HCV-positive donor

kidney which may reduce deceased donor kidney waiting time considerably.

Histological evidence of liver cirrhosis has been regarded as a contraindication to solitary kidney transplantation due to the risk of frank hepatic decompensation after transplantation as a consequence of immunosuppression. However, recent studies suggest that kidney alone transplant may be safe in end stage kidney disease (ESKD) patients with compensated hepatitis C (HCV) cirrhosis and hepatic portal venous gradient (HPVG) of less than 10 mmHg. In a

transplant candidates.

Peripheral vascular disease is present in a significant number of renal transplant recipients and is associated with increased morbidity and mortality. Vascular imaging with either a Doppler ultrasound, computed tomography (CT) scan or magnetic resonance angiography (MRA) of the pelvic vasculature is indicated in patients with a history of claudication and/or signs of diminished peripheral arterial pulses (particularly in diabetics) on physical exam. Our single-center experience reveals that in asymptomatic patients with diminished pedal pulses but good femoral pulses, screening has not resulted in intervention in any cases. An‐ giogram should be considered if noninvasive studies suggest the presence of large-vessel disease. Significant aortoiliac disease requires evaluation by the surgical transplant team and may preclude transplantation.

In transplant candidates with autosomal dominant polycystic kidney disease, screening for intracranial aneurysm with either CT scan or MRA is probably warranted in all patients with a history of headaches, stroke and/or family history of intracranial aneurysm or cere‐ brovascular accident.

#### **2.5. Infections**

All patients should be assessed for common latent or active infections and questioned for a his‐ tory of infectious exposures. Active infections including diabetic foot ulcers and osteomyelitis must be fully treated prior to transplantation. A prior history of tuberculosis or untreated tuber‐ culosis exposure requires appropriate posttransplant prophylactic therapy. Patients with an es‐ tablished history of systemic coccidioidomycosis or histoplasmosis or those from an endemic area should undergo appropriate antibody testing. In addition, these patients should be in‐ formed of possible disease reactivation with immunosuppressive therapy and indefinite post‐ transplant azole prophylactic therapy. A history of immunization should also be obtained to assure adequate immunizations for common infections prior to transplantation (e.g. hepatitis B, pneumovax, and other standard immunization appropriate for age). Immunization update is mandatory for those who have undergone surgical splenectomy. Up-to-date recommendations for routine adult immunizations are available through the Centers for Disease Control and Pre‐ vention website www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule.pdf. Ide‐ ally, all potential transplant candidates should complete all recommended immunizations at least 4 to 6 weeks before transplantation to achieve optimal immune response and to minimize the possibility of live vaccine-derived infection in the posttransplant period. Household mem‐ bers, close contacts, and health care workers should also be fully immunized.

Infection with influenza A (H1N1) virus has emerged as an important cause of morbidity and mortality in the general and dialysis population worldwide. More importantly, infected patients on chronic dialysis treatment were found to have a 10-fold higher mortality rate compared to the general population (Marcelli et al., 2009). Recipients of solid organ transplants have also been suggested to be at risk for more severe disease (Kumar et al., 2010). In a multicenter cohort study consisting of 237 adult and pediatric solid organ transplant recipients with microbiological-confirmed influenza A H1N1 infection, 71% required hospitalization. Among 230 patients for whom data on complications were available, 32% had pneumonia, 16% were admitted to the intensive care units, and ten (4%) died.(Kumar et al., 2010) Hence, unless contraindicated, influenza A (H1N1) vaccine should be considered in all prospective transplant candidates.

aneurysm (Class IIb). Patients without clinical evidence of atherosclerosis may also be screened if they have 2 or more risk factors including hypertension, hyperlipidemia, cigarette smoking, family history of atherosclerosis manifested before age 60 in a first-degree relative, or family history of ischemic stroke (Class IIb). It is also reasonable to screen asymptomatic patients with a carotid bruit (Class IIa). Lastly, asymptomatic patients with known or suspected carotid ar‐ tery disease are recommended to undergo duplex ultrasonography studies (Class I) (Lentine et al., 2012). Evidence of significant stenosis requires vascular surgery consultation. If necessary, carotid endarterectomy should be performed prior to transplantation and patients should be symptom free for at least six months prior to transplantation. For those with milder carotid dis‐

Peripheral vascular disease is present in a significant number of renal transplant recipients and is associated with increased morbidity and mortality. Vascular imaging with either a Doppler ultrasound, computed tomography (CT) scan or magnetic resonance angiography (MRA) of the pelvic vasculature is indicated in patients with a history of claudication and/or signs of diminished peripheral arterial pulses (particularly in diabetics) on physical exam. Our single-center experience reveals that in asymptomatic patients with diminished pedal pulses but good femoral pulses, screening has not resulted in intervention in any cases. An‐ giogram should be considered if noninvasive studies suggest the presence of large-vessel disease. Significant aortoiliac disease requires evaluation by the surgical transplant team

In transplant candidates with autosomal dominant polycystic kidney disease, screening for intracranial aneurysm with either CT scan or MRA is probably warranted in all patients with a history of headaches, stroke and/or family history of intracranial aneurysm or cere‐

All patients should be assessed for common latent or active infections and questioned for a his‐ tory of infectious exposures. Active infections including diabetic foot ulcers and osteomyelitis must be fully treated prior to transplantation. A prior history of tuberculosis or untreated tuber‐ culosis exposure requires appropriate posttransplant prophylactic therapy. Patients with an es‐ tablished history of systemic coccidioidomycosis or histoplasmosis or those from an endemic area should undergo appropriate antibody testing. In addition, these patients should be in‐ formed of possible disease reactivation with immunosuppressive therapy and indefinite post‐ transplant azole prophylactic therapy. A history of immunization should also be obtained to assure adequate immunizations for common infections prior to transplantation (e.g. hepatitis B, pneumovax, and other standard immunization appropriate for age). Immunization update is mandatory for those who have undergone surgical splenectomy. Up-to-date recommendations for routine adult immunizations are available through the Centers for Disease Control and Pre‐ vention website www.cdc.gov/vaccines/schedules/downloads/adult/adult-schedule.pdf. Ide‐ ally, all potential transplant candidates should complete all recommended immunizations at least 4 to 6 weeks before transplantation to achieve optimal immune response and to minimize the possibility of live vaccine-derived infection in the posttransplant period. Household mem‐

bers, close contacts, and health care workers should also be fully immunized.

ease, neurology consultation and optimal medical management may be sufficient.

and may preclude transplantation.

12 Current Issues and Future Direction in Kidney Transplantation

brovascular accident.

**2.5. Infections**

Hepatitis B antigenemia does not preclude transplant candidacy. However, patients should be referred for a liver biopsy to assess the severity of liver disease because liver enzymes may be spuriously normal despite necroinflammatory changes on biopsy (Fabrizi et al., 2010). Transplant candidacy should be based on both liver histology and serologic evidence of HBV replication (i.e. HBV DNA and HBeAg positivity). In transplant candidates with active HBV replication, antiviral therapy should be initiated pretransplantation. The presence of histolog‐ ically mild liver disease does not preclude transplantation. However, patients should be forewarned that the introduction of immunosuppressive therapy in the posttransplant period can lead to progression of liver disease even in patients with histologically mild disease before transplantation. All patients with HBV should be placed on antiviral therapy after transplan‐ tation to prevent HBV reactivation and replication and progression of liver disease. Similar to HBV infection, liver biopsy is essential in the evaluation of transplant candidate with HCV because clinical and biochemical findings are unreliable indicators of the severity of liver disease in the dialysis population. The presence of minimal to mild chronic hepatitis (stages I and II) does not preclude transplantation. Pretransplantation antiviral treatment should be considered to prevent the progression of liver disease and protect the graft against HCVrelated glomerulonephritis (Fabrizi et al., 2010). It should be noted that there is currently no effective treatment for chronic hepatitis C in renal transplant recipients. Although treatment with interferon-α may result in clearance of HCV RNA in 25-50% of cases, rapid relapse following drug withdrawal is nearly universal. More importantly, interferon-α treatment has been shown to precipitate acute allograft rejection and graft loss and is currently not routinely recommended for renal transplant recipients with HCV infection. The use of interferon-α should be individualized at the discretion of the transplant nephrologist and hepatologist. Studies evaluating interferon-free regimens are currently underway (Yee et al., 2012). Hepatitis C positive transplant candidates should be given the option of receiving a HCV-positive donor kidney which may reduce deceased donor kidney waiting time considerably.

Histological evidence of liver cirrhosis has been regarded as a contraindication to solitary kidney transplantation due to the risk of frank hepatic decompensation after transplantation as a consequence of immunosuppression. However, recent studies suggest that kidney alone transplant may be safe in end stage kidney disease (ESKD) patients with compensated hepatitis C (HCV) cirrhosis and hepatic portal venous gradient (HPVG) of less than 10 mmHg. In a single center study consisting of 37 kidney alone HCV positive transplant recipients (n=9 with cirrhosis and n= 28 with no cirrhosis), none developed decompensation of their liver disease at 3-year follow-up although one patient in the non-cirrhosis group developed metastatic hepatocellular carcinoma 16 months after transplantation. One- and three-year graft survival rates were 75% and 75% *vs.* 92.1% and 75.1% for the cirrhosis and non-cirrhosis groups, respectively (P=0.72). The corresponding one- and three-year patient survival rates were 88.9% and 88.9% *vs.* 96.3% and 77.9%, respectively (P=0.76). Only recipient age and decreasing albumin levels were significantly associated with worse graft and patient survival. The authors concluded that kidney alone transplant may be safe in ESKD patients with compensated HCV cirrhosis and HPVG of less than 10 mmHg. (Paramesh et al., 2012). While limited studies suggest that combined liver-kidney transplant may be unnecessary in ESKD patients with compensated HCV cirrhosis and HPVG of less than 10 mmHg, patients with decompensated liver cirrhosis should be referred for combined liver-kidney transplant.

Of note, studies in end-stage kidney disease (ESKD) patients treated by dialysis or transplan‐ tation, and in patients with HIV/AIDS suggest that cancers can be categorized into ESKDrelated, immune deficiency-related, not related to immune deficiency or of uncertain status. ESKD-related cancers include kidney, urinary tract, thyroid and multiple myeloma (Steward et al., 2008). Hence screening for malignancy in adult kidney transplant candidates should focus on kidney and urinary tract particularly in dialysis-dependent ESKD patients. Serum immunofixation electrophoresis should be performed in all transplant candidates older than 60 years of age. Chronic hepatitis B and C infected individuals should be screened for liver cancer. Although thyroid carcinoma has been observed at increased frequency in dialysis patients compared with the general population, thyroid ultrasound is not part of routine pretransplant screening. It has been suggested that regular thyroid ultrasound is justified in dialysis patients although there have been no studies to confirm or refute this recommendation. Therefore, screening prospective renal transplant candidates for thyroid cancer should be done at the discretion of the clinicians. All suitable renal transplant candidate should have a baseline renal ultrasound to screen for renal neoplasm (discussed further under urologic evaluation).

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15

5 yrs if > 5 cm

2Oncology evaluation or consultation with the Israel Penn International Transplant Tumor Registry at www.ipittr.org

4In situ melanoma may require a shorter waiting period of 2 years (dermatology consultation is probably warranted) 5Early in situ (eg ductal carcinoma in situ) may only require 2-year wait. Individuals with advanced breast cancer (stage

**Most tumors: wait time ≥2 years**

Incidental renal cell carcinoma *In situ* carcinoma of bladder *In situ* carcinoma of cervix Basal cell carcinoma

Squamous cell carcinoma (skin) 2,3 **Waiting time ≥2-5 years2**

may be invaluable 3Surveillance

**No waiting time if cure at the time of transplantation**

Melanoma2,,4 5 yrs Wilms tumor 2 yrs Renal cell carcinoma 2 yrs if < 5cm

Breast carcinoma5 2-5 yrs Lymphoma 2-5 yrs Colorectal carcinoma 2-5 yrs Invasive bladder 2 yrs Uterine body 2 yrs Invasive cervical carcinoma 2-5 yrs 1Certain cancers may recur despite a tumor-free waiting period.

III or IV) should be advised against transplantation

**Table 5.** Malignancy and renal transplantation1,2

Infections with the human immunodeficiency virus (HIV) was once considered a contraindi‐ cation to transplantation due to early report of serious infectious complications and death following HIV infection transmitted from a transplanted organ or inadvertent transplantation of HIV-infected patients. However, with the advent of highly effective highly active antire‐ troviral agents (HAART) regimen, there have been changing views regarding transplantation in HIV positive patients. Currently, a number of transplant centers would consider transplan‐ tation in stable HIV patients, defined as those with an undetectable HIV viral load, CD4 lymphocyte count greater than 300/mm3 , and absence of opportunistic infections in the previous year. Specific recommendations may vary from center to center and a formal consultation with infectious disease is recommended.

#### **2.6. Malignancy**

Transplant recipients are at greater risk of developing both *de novo* and recurrent malignancy due to the use of immunosuppressants. As the incidence of malignancy increases with the intensity and duration of immunosuppression, a history of immunosuppressive therapy for the native kidneys represents an added risk for posttransplant malignancy. For patients who have had a history of malignancy, consultation with oncology is advisable. Table 5 provides the general guidelines for minimum tumor-free waiting periods for common malignancies. Among the pre-transplant treated cancers, the highest recurrence rates have been observed with multiple myeloma (67%), non-melanoma skin cancers (53%), bladder carcinomas (29%), sarcomas (29%), symptomatic renal cell carcinomas (27%), and breast carcinomas (23%) (Penn I, 1997). In an analysis of the Israel Penn International Transplant Tumor Registry involving 90 patients with a history of pretransplant prostate adenocarcinoma (77 renal, 10 heart, and 3 liver transplant recipients), prostate cancer recurrences were shown to be related to the stage of disease at initial diagnosis (Woodle et al., 2005). Tumor recurrence rates were 14%, 16%, and 33% for stage I, II, and III diseases, respectively. Hence, a longer waiting time may be necessary for more advanced disease. Most transplant centers adhere to standard cancer surveillance appropriate for age for all transplant candidates although the utility of such screening has been challenged by experts in the field (Danovitch GM, 2003).

Of note, studies in end-stage kidney disease (ESKD) patients treated by dialysis or transplan‐ tation, and in patients with HIV/AIDS suggest that cancers can be categorized into ESKDrelated, immune deficiency-related, not related to immune deficiency or of uncertain status. ESKD-related cancers include kidney, urinary tract, thyroid and multiple myeloma (Steward et al., 2008). Hence screening for malignancy in adult kidney transplant candidates should focus on kidney and urinary tract particularly in dialysis-dependent ESKD patients. Serum immunofixation electrophoresis should be performed in all transplant candidates older than 60 years of age. Chronic hepatitis B and C infected individuals should be screened for liver cancer. Although thyroid carcinoma has been observed at increased frequency in dialysis patients compared with the general population, thyroid ultrasound is not part of routine pretransplant screening. It has been suggested that regular thyroid ultrasound is justified in dialysis patients although there have been no studies to confirm or refute this recommendation. Therefore, screening prospective renal transplant candidates for thyroid cancer should be done at the discretion of the clinicians. All suitable renal transplant candidate should have a baseline renal ultrasound to screen for renal neoplasm (discussed further under urologic evaluation).


1Certain cancers may recur despite a tumor-free waiting period.

2Oncology evaluation or consultation with the Israel Penn International Transplant Tumor Registry at www.ipittr.org may be invaluable

3Surveillance

single center study consisting of 37 kidney alone HCV positive transplant recipients (n=9 with cirrhosis and n= 28 with no cirrhosis), none developed decompensation of their liver disease at 3-year follow-up although one patient in the non-cirrhosis group developed metastatic hepatocellular carcinoma 16 months after transplantation. One- and three-year graft survival rates were 75% and 75% *vs.* 92.1% and 75.1% for the cirrhosis and non-cirrhosis groups, respectively (P=0.72). The corresponding one- and three-year patient survival rates were 88.9% and 88.9% *vs.* 96.3% and 77.9%, respectively (P=0.76). Only recipient age and decreasing albumin levels were significantly associated with worse graft and patient survival. The authors concluded that kidney alone transplant may be safe in ESKD patients with compensated HCV cirrhosis and HPVG of less than 10 mmHg. (Paramesh et al., 2012). While limited studies suggest that combined liver-kidney transplant may be unnecessary in ESKD patients with compensated HCV cirrhosis and HPVG of less than 10 mmHg, patients with decompensated

Infections with the human immunodeficiency virus (HIV) was once considered a contraindi‐ cation to transplantation due to early report of serious infectious complications and death following HIV infection transmitted from a transplanted organ or inadvertent transplantation of HIV-infected patients. However, with the advent of highly effective highly active antire‐ troviral agents (HAART) regimen, there have been changing views regarding transplantation in HIV positive patients. Currently, a number of transplant centers would consider transplan‐ tation in stable HIV patients, defined as those with an undetectable HIV viral load, CD4

previous year. Specific recommendations may vary from center to center and a formal

Transplant recipients are at greater risk of developing both *de novo* and recurrent malignancy due to the use of immunosuppressants. As the incidence of malignancy increases with the intensity and duration of immunosuppression, a history of immunosuppressive therapy for the native kidneys represents an added risk for posttransplant malignancy. For patients who have had a history of malignancy, consultation with oncology is advisable. Table 5 provides the general guidelines for minimum tumor-free waiting periods for common malignancies. Among the pre-transplant treated cancers, the highest recurrence rates have been observed with multiple myeloma (67%), non-melanoma skin cancers (53%), bladder carcinomas (29%), sarcomas (29%), symptomatic renal cell carcinomas (27%), and breast carcinomas (23%) (Penn I, 1997). In an analysis of the Israel Penn International Transplant Tumor Registry involving 90 patients with a history of pretransplant prostate adenocarcinoma (77 renal, 10 heart, and 3 liver transplant recipients), prostate cancer recurrences were shown to be related to the stage of disease at initial diagnosis (Woodle et al., 2005). Tumor recurrence rates were 14%, 16%, and 33% for stage I, II, and III diseases, respectively. Hence, a longer waiting time may be necessary for more advanced disease. Most transplant centers adhere to standard cancer surveillance appropriate for age for all transplant candidates although the utility of such screening has been

, and absence of opportunistic infections in the

liver cirrhosis should be referred for combined liver-kidney transplant.

lymphocyte count greater than 300/mm3

14 Current Issues and Future Direction in Kidney Transplantation

**2.6. Malignancy**

consultation with infectious disease is recommended.

challenged by experts in the field (Danovitch GM, 2003).

4In situ melanoma may require a shorter waiting period of 2 years (dermatology consultation is probably warranted)

5Early in situ (eg ductal carcinoma in situ) may only require 2-year wait. Individuals with advanced breast cancer (stage III or IV) should be advised against transplantation

**Table 5.** Malignancy and renal transplantation1,2
