Kidney Transplantation: Overview


1902

Vienna Medical School Austria: Kidney transplantation in animals

• Dr. Emerich Ullman: Autotransplant in a dog from normal position to vessels in the neck

• Dr. Alfred von Decastello: Dog-to-dog kidney transplantation

• Dr. Ullman: Dog-to-goat kidney transplantation

1906

Lyon, France: Xenograft transplantation

• Mathieu Jaboulay: Two xenograft kidney transplants (pig and goat as donors, to human recipients)

• Functioned for 1 h

1909

Lyon, France: Animal/human kidney transplant experiments

• Dr. Ernst Unger:

– Fox terrier to boxer: Kidney functioned for 14 days

– Human stillborn child to baboon: No kidney function

– Ape to human: No kidney function

• Resulted in the recognition of a “biochemical barrier” that hindered successful transplantation

1933

Ukraine, Soviet Union: First human-human kidney transplantation

• Dr. Yu Yu Voronoy: Human kidney blood group B to recipient blood group O: No kidney function

• (By 1949) Six such transplants with no kidney function in any of the subjects

1940s

University of London: Early experiments on immunologic basis of organ transplantation and immunosuppression

• Sir Peter Medawar

1946

Peter Bent Brigham Hospital, Boston

• Drs Hufnagel, Hume, and Landsteiner: Human allograft kidney transplant to arm vessels under local anesthesia; brief period of function

• Renewed interest in transplantation

Early 1950s

Increase in experimental and clinical kidney transplantation

Recognition of the role of immunology and graft failure/rejection

• Dr. Simonsen reported on the mechanism of kidney rejection

• Dr. Dempster discovered that radiation delayed rejection

• Dr. Hume observed that the blood group matching of graft and donor might be necessary

Early attempts at immunosuppression

• Total body irradiation and allograft bone marrow rescue

– Difficult to manage

– Graft vs. host disease frequent

• High-dose steroids

1954

Boston: Transplant of a kidney from one twin to another twin, the first successful kidney transplant ever performed

Early 1960s

Introduction of azathioprine, 6-mercaptopurine, and methotrexate

Mid-1960s

Donor organ cooling accepted

Low-dose steroids as effective as high-dose steroids

Late 1960s to 1970s

Development and improvement in HLA cross-matching

1980s to present

Ongoing improvements and advances

• Cyclosporine, tacrolimus, mycophenolate mofetil, and other immunosuppressive agents

• Improvement in techniques for organ procurement and preservation



Although dialysis is not a prerequisite for transplantation listing, the majority of patients undergoing kidney transplantation are on dialysis by the time they receive a kidney. Outcomes of kidney transplantation are negatively affected by prolonged periods on dialysis, and preemptive transplantation is associated with improved patient and graft survival [1, 2]. Patients can be listed once their estimated GFR is below 20 ml/min/1.73 m2 and/or if they can identify a potential living donor. The pre-transplant evaluation process can take some time and can delay addition to the waitlist. As such, early referral is recommended in the setting of chronic kidney disease, especially in diabetics and those with rapid clinical progression to end-stage renal disease. An estimated GFR less than 30 ml/min/1.73 m2 has been defined as the trigger for evaluation in some institutions [2]. A thorough pre-transplant evaluation is then undertaken to optimize the patient’s condition prior to transplantation and maximize graft and patient survival as well as quality of life.



Recipient Evaluation


Candidates for renal transplantation are evaluated extensively to identify any medical or psychosocial factors that may result in an adverse outcome. Patients with ESRD often have associated comorbidities such as anemia and platelet dysfunction, bone and joint disease, gastritis, gastrointestinal bleeding, ileus, pulmonary edema, pleural effusions, hepatic disorders, and cardiovascular abnormalities. Of particular significance is the effect of ESRD on the cardiovascular system. Patients undergoing hemodialysis have a cardiovascular mortality rate 30 times that of non-uremic patients [1]. This increased risk is attributed to increased atherosclerosis, myocardial infarction, congestive heart failure, dysrhythmias, pericardial effusions, and cardiomyopathy. The presence of hypertension, hyperlipidemia, and diabetes is also common within this patient population. The purpose of the pre-transplant evaluation is to identify and treat coexisting medical problems that would increase a patient’s morbidity and mortality after transplantation. It also identifies any psychosocial factors that may have a negative effect on outcomes. These factors include any financial difficulties, uncontrolled psychological issues, lack of social support, and history of medical noncompliance.

The evaluation process begins with a thorough history of the patient’s renal disease. The etiology and pathology of ESRD can determine the risk of recurrence as well as define the associated comorbidities that will require further investigation. Other pertinent information includes dialysis status and dialysis access, urine production, any complications associated with dialysis access, thrombotic events, blood transfusions, and infections. Furthermore, it is important to determine if the patient has a history of prior transplantation, rejection episodes, allograft infections, or noncompliance. Knowing the outcome of a prior transplant may be predictive of the outcome of the subsequent transplant.

Recipient evaluation continues with an extensive review of the patient’s medical history. This is to identify further any risk factors that would predict increased morbidity and mortality as well as any contraindications to transplantation. Of particular importance are cardiopulmonary symptoms, such as angina, history of myocardial infarction, pericarditis, pericardial effusion, valve disease, and congestive heart failure. Identification of these risk factors will determine the degree of workup necessary for cardiac clearance. Cardiac testing includes an electrocardiogram, echocardiogram, stress test, and possible coronary angiogram. A history of type I diabetes would also lead to the need for an aggressive cardiac workup, given the increased risk of silent coronary disease. Furthermore, the evaluation will also include an assessment of pulmonary, neurologic, psychologic, and urologic symptoms. This information will guide the need for additional testing such as pulmonary function testing, voiding cystourethrogram, carotid duplex, and neurovascular imaging. Screening for occult malignancy and inquiring about a history of malignancy are also part of the process. An infectious disease profile is obtained to determine exposure and risk factors for tuberculosis, HIV, and hepatitis B and C. Prior surgeries, medications, allergies, and social history are also pertinent. Overall, this process serves to identify any conditions that would require further investigation.

The physical exam highlights any clinical signs that may warrant further investigation. The vital signs may reveal such symptoms as uncontrolled hypertension or orthostatic hypotension. Carotid bruits may be a marker of significant carotid stenosis. Pulmonary and cardiac findings may identify underlying disease that may not have been fully evident in the patient’s history. Abdominal exam may reveal scars of prior surgery or signs of an intra-abdominal process. Weak femoral and peripheral pulses may require additional workup to evaluate possible peripheral vascular disease. Finally, an assessment would screen for infections.

Extensive laboratory and imaging studies serve as screening tools to identify factors that will impact transplantation negatively. Not all procedures and tests are required for every patient. Rather, the need for a given study is guided by the patient’s age, history, physical exam, and inherent risk factors. Patients with a significant medical history, positive review of systems, type I diabetes, or hypertensive renal disease should undergo a complete cardiac workup including a coronary angiogram. Finding significant coronary artery disease results in a cardiologist evaluation for revascularization by coronary angioplasty with stenting or coronary artery bypass grafting prior to transplantation.

Immunologic evaluation is performed to identify factors associated with a high risk for antibody-mediated hyperacute rejection. This involves ABO blood group antigen determination, HLA typing, percent panel reactive antibody level (PRA), and donor/recipient cross-matching. ABO blood group antigens are potential targets for the recipient’s preformed cytotoxic anti-ABO antibodies. This may result in antibody-mediated hyperacute rejection in ABO-incompatible donor-recipient groups. All transplant recipients and donors are HLA typed to determine the HLA class I and class II loci. Six major and multiple minor HLA antigens are identified, and the degree of incompatibility is determined by the number of antigens that are mismatched at each loci. Better outcomes have historically been noted with a zero antigen mismatch. The PRA is used to evaluate the recipient’s sensitivity to HLA phenotypes in a given population. The recipient can become sensitized as a result of prior blood transfusions, transplants, or pregnancy. Cross-matching is used to determine if the recipient has any preformed anti-HLA antibodies specific to the prospective donor. The immunologic profile is also of particular importance with regard to organ allocation. The degree of mismatching can affect allocation of deceased donor kidneys. Organ allocation also takes into consideration individuals with a high (>95 %) PRA found to have a negative cross-match with a particular donor.

The evaluation process can be summarized by answering five basic questions:


  1. 1.


    What is the cause of renal failure?

     

  2. 2.


    Is a renal transplant indicated?

     

  3. 3.


    Are there any medical barriers to transplantation?

     

  4. 4.


    Are there any psychological or social barriers to transplantation?

     

  5. 5.


    Are there any immunologic barriers that would negatively affect transplantation?

     

This extensive evaluation process systematically answers these questions and identifies the patients who can be listed for kidney transplantation (see Table 19.2). It further identifies those with contraindications to transplant (see Table 19.3). The process also brings to attention those who would benefit from additional testing or intervention prior to a decision regarding transplantation.


Table 19.2
Pre-transplant evaluation [3]















































































1. History of renal disease

(a) Etiology

(b) Dialysis status

(c) Urine production

(d) Prior transplants and complications

(e) Review of systems

2. Past medical and surgical history

(a) History of blood transfusion

(b) Comorbid diseases

3. Physical examination

4. Gynecologic evaluation

(a) Pap smear

5. Mammography

6. Dental evaluation

7. Laboratory studies

(a) Complete blood count, chemistries, liver function tests, coagulation profile, parathyroid hormone level

(b) Malignancy screen: PSA

(c) Serologies: CMV, EBV, Varicella-Zoster, HIV, RPR, PPD, hepatitis B and C

(d) Urinalysis and urine culture

(e) Immunologic profile: Blood type, panel reactive antibody, HLA typing

8. Chest X-ray, abdominal ultrasound, CT scan of abdomen and pelvis (if indicated)

9. GI workup

(a) Upper endoscopy (if indicated)

(b) Colonoscopy (if indicated)

10. Cardiac workup

(a) EKG

(b) Echocardiogram

(c) Stress test (if indicated)

(d) Coronary angiogram (if indicated)

11. Vascular workup (if indicated)

(a) Lower extremities duplex

(b) Carotid duplex

(c) Cerebral imaging

12. Pulmonary workup (if indicated)

(a) Pulmonary function test

(b) Right-heart catheterization

13. Psychosocial evaluation



Table 19.3
Contraindications to kidney transplantation [3]



























 1. Reversible renal disease

 2. Active infection

 3. Chronic untreated infection

 4. Active glomerulonephritis

 5. Advanced/uncorrectable coronary or pulmonary disease

 6. Life expectancy less than 1 year

 7. Recent/untreated malignancy

 8. Noncompliance

 9. Active substance abuse

10. Uncontrolled psychiatric disorders

11. Lack of adequate social support


Living Donor Kidney Donation


A major limitation in kidney transplantation is deceased donor organ availability; some patients are fortunate enough to have a living donor. The major concern is the risk of subjecting a healthy patient to a nephrectomy. However, the morbidity associated with the procedure is less than 1 %, with a mortality 0.03 %. Donor life expectancy does not appear to be negatively affected and has been shown to be longer than that of the general population [3, 4].

The goal of the evaluation process for living donors is to establish that the potential donor is healthy enough to donate. As such, it is necessary to identify any underlying history that would suggest underlying renal dysfunction that would be negatively impacted by the loss of a kidney through donation (Tables 19.4, 19.5, and 19.6). Disease states such as hypertension and diabetes can affect renal function. A history of gestational diabetes is also of concern with a potential risk for type 2 diabetes later in life. In addition, the evaluation assesses a history of recurrent urinary tract infections, kidney stones, or prior renal trauma. A history of clotting disorders, deep vein thrombosis, heart disease, lung disease, or obesity serves as a possible indication of increased risk of donor morbidity and mortality.


Table 19.4
Evaluation of a potential living kidney donor [5]



































































































 1. Identification of potential living donor

 2. History and physical examination

• Personal/family history of kidney disease

• Hypertension

• Diabetes/gestational diabetes

• Urinary tract infections

• Kidney stones

• History of DVTs or clotting disorders

• Heart/lung disease

• Cancer history

• Kidney injury history

• Use of NSAIDs

• Body-mass index/obesity

 3. Immunologic evaluation

• ABO blood type

• HLA determination

• Cross-match

 4. Psychosocial evaluation

 5. Laboratory studies

• Complete blood count, chemistries, liver function panel, coagulation panel

 6. Metabolic profile

• Fasting blood glucose

• Thyroid function test

• Uric acid level

• Fasting lipid profile

 7. Urine studies

• Urinalysis, 24-h urine protein and creatinine, GFR

• ± Renal scan with differential renal function

 8. Infectious profile

• Hepatitis A, B, and C serologies

• CMV/EBV serologies

• HIV/HTLV/RPR

• Urine culture

• PPD

 9. Cancer screen

• Prostate-specific antigen (males >50 years)

• Pap smear (women)

• Mammogram (women >40 years, family history)

• Colonoscopy (age >50, family history)

10. Other

• Pregnancy test

• EKG

• ± Echocardiogram/stress test/coronary angiogram

11. Radiologic studies

• Chest X-ray/chest CT

• Renal ultrasound

• Renal CT scan with 3D angiography



Table 19.5
Absolute contraindications to living kidney donation [5]















































1. Age <18 years

2. Hypertension (BP > 130/90)

• In donor age less than 50 years old

• Evidence of end-organ damage

• On two or more antihypertensive medications

3. Diabetes (diagnosis of diabetes)

4. Abnormal glucose tolerance test 2 h OGTT > 140

5. History of thrombosis or embolism

6. Psychiatric contraindications

7. Obesity: BMI > 35 kg/m2

8. Coronary artery disease

9. Symptomatic valvular disease

10. Chronic lung disease with impairment of oxygenation or ventilation

11. Recent malignancy, or cancers with long times to recurrence

• Breast cancer

12. Urologic abnormalities of donor kidney

13. Creatinine clearance <80 ml/min/1.73 m2, or projected GFR with removal of one kidney at 80 years old of <40 cc/min/1.73 m2

14. Peripheral vascular disease

15. Proteinuria >300 mg/24 h

16. HIV infection (unless recipient is HIV positive)

17. Hepatitis C virus infection

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Jul 9, 2017 | Posted by in Uncategorized | Comments Off on Kidney Transplantation: Overview
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