Evaluation of the Potential Kidney Transplant Candidates

Evaluation of the Potential Kidney Transplant Candidates

Phuong-Thu T. Pham

Son V. Pham

Michael S. Lee

Basmah Abdalla

Suphamai Bunnapradist

Phuong-Chi T. Pham


  • Kidney transplantation is the treatment of choice for suitable candidates with end-stage kidney disease (ESKD).

    • It confers survival advantage over remaining on dialysis across all ages and in both diabetic and nondiabetic transplant recipients.

    • It offers long-term economic benefits compared to dialysis.

  • Early referral to a transplant program is advisable. Patients should be informed that referral does not imply immediate transplantation, nor does it indicate they are suitable candidates for kidney transplantation.

  • Preemptive transplantation (transplantation before the commencement of dialysis) improves patient and graft survival. It is suggested that transplantation prevents cardiovascular complications associated with long-term dialysis.1

    • Studies show that preemptive transplantation is underused.2

    • Potential barriers to preemptive transplantation2: late referral to a nephrologist or transplant center, patient denial, lack of patient education on ESKD treatment modalities or living donor transplantation option. The complexity of the transplant evaluation process and misconception by nephrologists have also been suggested to play a contributory role (eg, nephrologists may underestimate the benefits of transplantation over remaining on dialysis in black patients, or “kidney function is severely diminished but “stable”).2

    • Identification of potential “modifiable” barriers may improve preemptive transplantation rates.

  • In the United States, transplant candidates with an estimated glomerular filtration rate (eGFR) of ≤20 mL/min/1.73 m2 begin to accrue waiting time once they are registered on the deceased donor waiting list. Qualified candidates whose transplant referral occurs after dialysis initiation may accrue waiting time retrospectively (waiting time starts from the day of dialysis initiation).


  • Routine assessment of a kidney transplant candidate includes the following:

    • Thorough history and physical examination

    • Psychosocial evaluation

    • Psychiatric evaluation as needed

    • Routine laboratory testing and imaging studies (outlined in Tables 4-1 and 4-2)

    • Patient education session

  • Absolute and relative contraindications to transplantation are outlined in Table 4-3.


  • Cardiovascular and valvular heart disease (VHD)

    • Cardiovascular disease (CVD)/Coronary artery disease (CAD)

      • CVD is the leading cause of death after kidney transplantation.

      • Deaths with a functioning graft occurring within 30 days after transplantation are due to CAD in nearly half of the cases.3

      • Cardiovascular screening

        • image CVD screening is an essential component of the transplant evaluation process because of the high prevalence of clinically silent CAD among ESKD patients. Ideally, transplant centers should have a designated cardiologist to assist in the evaluation and management of CVD in moderate to moderately high-risk kidney transplant candidates.

        • image Controversies exist regarding the best strategy for pretransplant assessment and management of CAD to prevent adverse perioperative cardiac events.

        • image The American Society of Transplantation recommends a cardiac stress test in high-risk renal transplant candidates. High-risk candidates are defined as patients with diabetes mellitus (DM), prior history of CAD, abnormal electrocardiogram, or age of 50 years or older.4

        • image DM and CVD

          • DM is considered a CAD risk equivalent by the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP) guidelines.5

          • Data from the Framingham Heart Study/National Heart, Lung, and Blood Institute showed that having DM significantly increased the risk of developing CVD (hazard ratio 2.5 for women and 2.4 for men) and dying when CVD was present (hazard ratio 2.2 for women and 1.7 for men).6

          • Diabetic patients with CAD may not develop typical angina symptoms or may be asymptomatic.

          • Screening for covert CAD must be considered in all prospective diabetic kidney transplant candidates, particularly among type 1 diabetics.

      • Screening strategies

        • image Noninvasive testing or coronary angiography should be performed based on the individual’s perceived risk of CAD.

        • image Pharmacologic or nuclear stress test is recommended in dialysis patients who cannot achieve an adequate exercise level.

        • image Coronary angiography

          • American Society of Transplantation: Coronary angiography should be considered only in patients with a positive stress test.4 However, over the years, this strategy has been challenged due to the reduced sensitivity and specificity of noninvasive testing in kidney transplant patients compared with those of the general population.

          • A number of transplant centers recommend coronary angiography in highrisk patients (see Figure 4-1).

        • image There are insufficient data to recommend use of the following for the screening of CAD in kidney transplant candidates as screening tools: single-photon emission computed tomography (CT), positron emission tomography, or electronbeam CT.

          TABLE 4-1 Pretransplant Routine Laboratory Testing and Imaging Studies

          Laboratory evaluation

          Comprehensive metabolic panel

          Complete blood count with platelets

          Prothrombin time panel (INR and PTT)

          Urinalysis and urine culture

          Hepatitis B (surface Ag, IgM and IgG core Ab, and surface Ab)

          HCV Ab screening (if positive, check PCR confirmatory test)

          HIV1/HIV2 antibody screen

          CMV-specific IgG

          EBV-VCA IgM/EBNA1 IgG panel

          RPR or VDRL (FTA-ABS confirmatory test if positive RPR or VDRL)

          Iron and iron binding capacity, ferritin

          Type and screen

          Coccidioides IgG/IgM EIA (recommended for patients with history of valley fever or those who live in endemic areas)

          Optional: serum immunofixation electrophoresis if age >60 y old (Currently, routine testing transplant candidates for MGUS is not recommended. However, practice may differ among centers.)

          Special laboratory evaluation

          Hypercoagulability panel in patients with history of recurrent thrombosis or spontaneous fetal losses

          PSA screening for men with family history, obstructive voiding symptoms, or hematuriaa

          Other evaluation


          Chest x-ray

          PPD skin test or preferably the interferon-γ release assays (QuantiFERON-TB Gold Test)

          Renal ultrasound to assess for acquired cystic disease or mass

          Abdominal ultrasound in diabetics to evaluate for gallstones

          Cardiac evaluation (myocardial perfusion study or stress test with imaging—choice of cardiac studies differ among centers; echocardiogram to assess ejection fraction)

          Colonoscopy screening (see Table 4-2)

          Pap smear and mammogram screening (appropriate for age similar to the general population)

          Urologic evaluation if history of bladder/voiding dysfunction, recurrent urinary tract infections, or history of urologic abnormalities

          Immunologic studies

          Blood group and HLA typing

          Anti-HLA antibodies screening by Luminex technology (see chapter 1)

          Sera for crossmatch

          Abbreviations: Ab, antibody; Ag, antigen; CMV, cytomegalovirus; EBNA1, Epstein-Barr nuclear antigen 1; EBV, Epstein-Barr virus; EIA, enzyme immunoassay; FTA-ABS, fluorescent treponemal antibody absorption; HCV, hepatitis C virus; HLA, human leukocyte antigen; IgG, immunoglobulin G; IgM, immunoglobulin M; INR, international normalized ratio; MGUS, monoclonal gammopathy of undetermined significance; PCR, polymerase chain reaction; PPD, purified protein derivative; PSA, prostate-specific antigen; PTT, partial thromboplastin time; RPR, rapid plasma reagin; VCA, viral capsid antigen; VDRL, Venereal Disease Research Laboratory.

          a Routine screening may be more harmful than protective because it does not appear to confer a survival benefit and may delay listing and decrease transplantation rates (single-center study, n = 3,782 men ≥18 y of age undergoing primary kidney transplant evaluation).

          TABLE 4-2 Pretransplant Colonoscopy Screening

          For “average-risk” individuals (no family history of colorectal cancer and no risk factors listed in the right column)

          For “increased-risk” individuals (defined below)

          • Most individuals: Screening begins at age 50 y.

          • African Americans: Screening begins at age 45 y.

          • Repeat colonoscopy every 10 y if no polyps are found.

          • Comorbid conditions present (diabetes, obesity, significant smoking, or alcohol use): Consider repeat colonoscopy prior to transplant if >5 y have elapsed.

          • Patients with a current colonoscopy in the past 10 y may proceed with transplant if preparation was considered high quality by the endoscopist; otherwise, repeat colonoscopy should be considered.

          Family history of colon cancer in first-degree relative <60 y at diagnosis

          • Screening begins 10 y prior to the family member’s age at diagnosis or age 40 y whichever comes first.

          • If no polyps found: Repeat colonoscopy every 5 y.

          Family history of colon cancer in first-degree relative >60 y at diagnosis

          • Screening begins at age 50 y.

          • If no polyps found: Repeat colonoscopy every 10 y.

          • Comorbid conditions present (DM, obesity, significant smoking, or alcohol use): Consider colonoscopy 10 y prior to the family member’s age at diagnosis or 40 y whichever comes first.

          History of abdominal radiation (>30 Gy)

          • Screening begins 10 y after radiation exposure or age 35 y whichever comes first.

          • If no polyps found: Repeat colonoscopy every 10 y.

          Inflammatory bowel disease (IBD) without primary sclerosing cholangitis

          • Screening begins 8 y after IBD diagnosis (ulcerative colitis and Crohn colitis).

          • Random biopsies should be taken.

          • Repeat colonoscopy every 1-2 y.

          Primary sclerosing cholangitis (PSC)

          • Screening begins at PSC diagnosis.

          • Random biopsies to evaluate for subclinical IBD

            • Biopsies show no IBD: Repeat colonoscopy every 5 y.

            • IBD confirmed on biopsies: Repeat colonoscopy every 1-2 y.

          Familial colon cancer syndromes

          • Screening begins at various ages dependent on the syndrome.

          Cystic fibrosis

          • Consider screening at age 40 y.

          • If no polyps found: Consider repeat colonoscopy every 5 y.

          Abbreviation: DM, diabetes mellitus.

          Prenner S, Levitsky J. Comprehensive review on colorectal cancer and transplant. Am J Transplant. 2017;17(11):2761-2774.

          Recommendations based on U.S. Preventive Services Task Force and American College of Gastroenterology Guidelines.

          TABLE 4-3 Contraindications to Kidney Transplantation

          Absolute contraindications

          Recenta or active malignancy, metastatic malignancy

          Untreated current infection or ongoing nonhealing ulcers

          Severe irreversible extrarenal disease (eg, severe cardiovascular disease not amenable to intervention or severe pulmonary disease)

          Life expectancy <2 y

          Recalcitrant treatment nonadherence

          Poorly controlled psychiatric illnesses

          Active substance abuse

          Aggressive native kidney diseaseb

          Limited, irreversible rehabilitation potential

          Decompensated liver cirrhosis (unless combined kidney-liver transplantation)

          Primary oxalosis (Consider combined kidney-liver transplantation.)

          Chronic severe and uncorrectable hypotension (may compromise posttransplant graft perfusion potentially leading to graft primary nonfunction)

          Relative contraindications

          Morbid obesity (center dependent, see text)

          Advanced age (center-dependent—consensus on upper age limit is lacking, see text)

          History of multiple myeloma or plasma cell dyscrasia (assess on a case-by-case basis, see text)

          Special considerationsc

          ABO incompatibility

          Positive T-cell crossmatch

          Postpercutaneous coronary intervention (PCI) patients. Transplant surgery not recommended

          Within 4 wk of coronary revascularization with balloon angioplasty

          Within 1 mo of bare metal stent placement

          Within 6 mo of drug-eluting stent (DES) placement (with the newer generation DES)

          a Please see table 4-4

          b See chapter 8, Glomerular disease recurrence after transplantation.

          c Pretransplant preconditioning regimen or desensitization protocols may allow successful transplant across these barriers.

          Other options: paired donor exchange with or without desensitization, desensitization on waitlist.

        • image The authors’ proposed algorithm for initial pretransplant cardiac evaluation is shown in Figures 4-1, 4-2 and 4-2. Continued cardiac surveillance for wait-listed patients is discussed in chapter 6.

      • Listing is possible (practice may differ among centers):

        • image Patients undergoing successful revascularization can be listed or transplanted if they also meet the following criteria:

          • For patients after coronary artery bypass grafting (CABG): cardiac rehabilitation per the American College of Cardiology/American Heart Association (ACC/AHA) guidelines and at least 6 months post-CABG

          • For patients with stable ischemic heart disease after coronary stenting: at least 1 month of dual antiplatelet therapy (DAPT) after bare metal stent placement and at least 6 months of DAPT after drug-eluting stent placement

          • For patients with acute coronary syndrome after coronary stenting: at least 12 months of DAPT after bare metal stent or drug-eluting stent placement

        Figure 4-1 Proposed Algorithm for Initial Pretransplant Cardiac Evaluation

        CABG, coronary artery bypass grafting; CAD, coronary artery disease; CHF, congestive heart failure; DM, diabetes mellitus; ECG, electrocardiogram; PCI, percutaneous coronary intervention; SPK, simultaneous pancreas kidney.

        aTraditional: hypertension, hyperlipidemia, DM, tobacco use, family history of CAD, age >45 years for male, age >55 years for female.

        Figure 4-2 Abnormal Coronary Angiogram

        ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CABG, coronary artery bypass grafting; CAD, coronary artery disease; FFR, fractional flow reserve; MPS, Myocardial perfusion study; PCI, percutaneous coronary intervention.

        aDiscussion of revascularization options (i.e. CABG vs. PCI) is beyond the scope of this chapter

      • Listing is contraindicated.

        • image Severe CAD not amenable to percutaneous or surgical revascularization

        • image Cardiomyopathy with an ejection fraction of < 40% generally precludes kidney transplantation. Referral to cardiology is recommended.

      • Combined kidney-heart transplantation may be a therapeutic option for selected patients with severe CAD not amenable to revascularization with percutaneous coronary intervention or CABG and those with severe nonischemic cardiomyopathy. Discussion is beyond the scope of this chapter.

    • VHD7

      • Valvular calcifications

        • image Calcified aortic stenosis and VHD are common among patients with ESKD on maintenance dialysis.

        • image Mitral annular calcification occurs in 10% to 50% of patients with ESKD.

        • image Aortic valve calcification develops in 25% to 55% of hemodialysis patients and occurs 10 to 20 years earlier than in the general population.

        • image Calcifications of the tricuspid and pulmonic valves are rare.

        • image Potential predisposing or risk factors for valvular calcifications: dialysis duration, advanced age, secondary hyperparathyroidism, elevated calcium-phosphorus product, hypercalcemia, and hyperphosphatemia. Other suggested risk factors include hypertension, DM, hyperlipidemia, left ventricular hypertrophy, uremic milieu, and anemia.

      • Valvular thickening, or sclerosis, which most commonly involves the aortic and mitral valves, is a frequent finding in hemodialysis patients. Among such patients, aortic and mitral valve sclerosis occur in 55% to 69% and 40% to 60% of individuals, respectively.

      • Previously thought to have no clinical significance but has now been recognized as a potential cause for progressive stenosis and cardiovascular mortality

      • Management of VHD

        • image The Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients recommends following the ACC/AHA guidelines to evaluate dialysis patients for the presence of VHD8:

          • Echocardiogram should be performed in patients with suspected VHD.

          • Dry weight optimization should be achieved prior to testing to improve accuracy of result interpretation.

  • Cerebrovascular and peripheral vascular disease

May 8, 2019 | Posted by in NEPHROLOGY | Comments Off on Evaluation of the Potential Kidney Transplant Candidates

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