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
Psychiatric evaluation as needed
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
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.
Controversies exist regarding the best strategy for pretransplant assessment and management of CAD to prevent adverse perioperative cardiac events.
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
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.
Noninvasive testing or coronary angiography should be performed based on the individual’s perceived risk of CAD.
Pharmacologic or nuclear stress test is recommended in dialysis patients who cannot achieve an adequate exercise level.
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).
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
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
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
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
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.
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
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)
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)
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.
Listing is possible (practice may differ among centers):
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
Listing is contraindicated.
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.
Aortic valve calcification develops in 25% to 55% of hemodialysis patients and occurs 10 to 20 years earlier than in the general population.
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
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
Screening for cerebrovascular and peripheral vascular disease
Routine screening of asymptomatic kidney transplant candidates for cerebrovascular disease is not warranted.
History of claudication, presence of carotid bruit, abdominal or femoral bruits, or diminished peripheral pulses (femoral, posterior tibialis, or dorsalis pedis) should prompt further evaluation with imaging studies as clinically indicated.
Adult polycystic kidney disease (APKD) patients with history of headache (or other central nervous system symptoms) or family history of intracranial aneurysm should undergo noninvasive screening with time-of-flight magnetic resonance angiogram (MRA) without gadolinium. Invasive CT angiogram should preferably be performed only when MRA is contraindicated (eg, prior surgical clipping of aneurysm with a magnetic resonance noncompatible clip).
Diabetic patients with a history of ischemic ulcerations of the lower extremities or claudication symptoms should undergo noninvasive studies with noncontrast CT of the pelvic vasculature. Angiography should be considered if noninvasive studies suggest the presence of large-vessel disease.9
Special considerations prior to transplantation: Patients on anticonvulsants who have significant drug-drug interactions with calcineurin inhibitors should be referred to neurology to assess whether these medications can be discontinued or replaced with newer generation anticonvulsants that do not interact with calcineurin inhibitors (see chapter 2 for drug-drug interactions).
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