Brenner and Rector's The Kidney, 8th ed.

CHAPTER 64. Donor and Recipient Issues

Hassan N. Ibrahim   Bertram L. Kasiske

  

 

The Evaluation of Kidney Transplant Candidates, 2126

  

 

Purpose, 2126

  

 

Timing of the Referral, 2126

  

 

Absolute Contraindications, 2126

  

 

Follow-up While on the Waiting List, 2130

  

 

Living Donors, 2130

  

 

Medical Evaluation of the Kidney Donor, 2130

  

 

Surgical Risk, 2131

  

 

Assessment of Renal Function in Kidney Donors Pre- and Postdonation, 2131

  

 

Consequences of Living with One Kidney, 2132

  

 

Postdonation Development of Diabetes and Risk of Nephropathy, 2133

  

 

Does Donation Place the Kidney Donor at Higher Cardiovascular Risk? 2133

  

 

Special Donor Situations, 2133

  

 

Conclusion, 2136

THE EVALUATION OF KIDNEY TRANSPLANT CANDIDATES

Purpose

The evaluation of candidates for kidney transplantation should minimize morbidity and mortality and, at the same time, maximize quality of life. Transplant candidates have dialysis as an alternative to transplantation, so deciding not to transplant a particular patient is not an automatic death sentence. Conversely, studies comparing transplant recipients to patients on the deceased donor transplant waiting list have shown that survival is better after kidney transplantation than on dialysis.[1] Furthermore, analyses of patient subgroups demonstrated that the survival advantage of transplantation extended to patients of any age, gender, ethnicity, and with diabetic or nondiabetic kidney disease.[1] However, waiting list patients (controls) were selected using existing practices and procedures. In addition, it is likely that at least some patients on the waiting list in these studies were no longer transplant candidates but had not been removed from the waiting list and were, therefore, not truly comparable with patients who were transplanted. Nevertheless, the survival advantage was at least twofold greater for transplant recipients than for waiting list patients, and it is unlikely that correcting methodologic flaws in these studies would erase this advantage.[1]

Another reason to evaluate transplant candidates is to protect living donors, and the scarce resource of deceased and living donor kidneys, from use in a transplantation that fails to benefit the recipient. This second goal is to avoid risking a living donor and/or “wasting” a kidney on a recipient who dies soon after transplantation. Physicians and transplant centers that evaluate recipients are advocating for, and representing the interests of, transplant candi-dates. However, indirectly they must also protect the interests of donors and society.

Given the importance of deciding who should undergo kidney transplantation, and how best to minimize risks and maximize outcomes, professional societies around the world have developed guidelines for the evaluation of candidates for kidney transplantation. [2] [3] [4] [5] These guidelines are intended to address regional and local variations in access to transplantation. However, they are not intended to be rigid documents that need to be strictly adhered to in all cases, but rather they are intended to provide a framework for decision-making that should be tailored to each individual patient.

Timing of the Referral

Recent observational studies suggest that survival after transplantation is incrementally worse the longer patients have been on dialysis before transplantation. Indeed, the best outcomes are seen in patients who are preemptively transplanted before dialysis is initiated.[6] Conversely, some patients have very slowly progressing kidney disease, and it makes little sense to perform a transplant months or even years before it is needed. In addition, some patients beleived to have end-stage renal disease (ESRD) may regain function. This can be seen, for example, in patients with poorly controlled hypertension, who regain function weeks, or even months, after good blood pressure control is established.

In general, patients who are not clinically uremic should not be transplanted until the estimated glomerular filtration rate (eGFR) is ≤15 mL/min or less or at least 20 mL/min. In the United States, patients can begin accruing waiting time (which most strongly determines when patients will be allocated a deceased donor kidney) only when the eGFR is 20 mL/min or less. The rate of progression is also an important consideration, however. Patient with diabetes, for example, may progress relatively rapidly, and when it is clear that the patient will require renal replacement therapy within the next few months, there is no sense in delaying transplantation if a living donor is available.

The evaluation of a transplant candidate, and the work-up of potential living donors, may take several months. It is best not to wait too long to refer patients for evaluation. When kidney disease is progressing and eGFR is 30 mL/min or less, it may be time to refer the patient to a transplant center. Primary physicians and nephrologists should use judgment in whom to refer for transplantation. When it is obvious that a patient is not a transplant candidate, a referral for transplant evaluation may give false hope to the patient and may, therefore, be inappropriate. When in doubt, call a transplant physician or surgeon at the transplant center and discuss the appropriateness and timing of a referral.

Absolute Contraindications

Most absolute contraindications to kid-ney transplantation are not irreversible contraindications. Absolute contraindications include life-threatening infections, cancer, unstable cardiovascular disease (CVD), and noncompliance. However, infections can often be effectively treated, cancers can be cured, organs threatened by occlusive arterial disease can be protected with revascularization procedures, and noncompliant patients can become compliant. Nevertheless, not every patient with stage 5 chronic kidney disease (CKD) is a transplant candidate.

In general, patients who would not be expected to survive more than 2 years with a kidney transplant should probably not undergo transplantation. If such a patient has a potential living donor, it may not be ethical to subject that donor to the risk of surgery when expected outcomes are poor. If such a patient does not have a potential living donor, he or she will be unlikely to survive long enough on the waiting list to receive a deceased donor kidney. The argument can also be made that a deceased donor kidney may result in greater benefit if it is allocated to a patient with a life expectancy greater than 2 years than if it is allocated to someone who is not expected to live that long. Physicians and transplant centers should inform patients when they are not transplant candidates, and they should not give the patients false hopes or expectations. It is not a good practice to place a patient on the waiting list who is not a good candidate, assuming that the patient will not survive long enough to be offered a kidney and/or intending to refuse an offered kidney if it is made available.

Age

Most agree that older age per se should not be an absolute contraindication to transplantation, but an elderly patient's overall physical condition, life expectancy, and chance for improvement in quality of life should be carefully considered. A living donor transplant is often the best option for an older patient, and a healthy relative, friend, or spouse of a similar age as the recipient may be a suitable donor. It is often difficult to decide on using a daughter or son as a donor when the potential recipient is much older. If the patient does not have a living donor, the potential recipient's condition will likely change during the time spent on the waiting list and frequent reassessment is mandatory. Some advocate that older donors, who can ill afford a lengthy sojourn on the waiting list, should consider accepting an extended criteria donor (ECD) kidney. In the United States, patients have the option of accepting an ECD (generally older) kidney in the Organ Procurement and Transplantation Network (OPTN) ECD program. However, outcomes are worse with ECD kidneys, whether or not the recipient is old.[7]

Infections

An active infection that is potentially life-threatening in an immunosuppressed patient is a contraindication to transplantation. Transplant candidates should be screened for potentially life-threatening infections, and vaccinations should be up to date. A number of infections should be considered ( Table 64-1 ).[8]

TABLE 64-1   -- Transplant Candidate Evaluation to Minimize Infection Risk

Infection

Screening

Action

HIV

HIV antibody

Transplant only if stringent conditions are satisfied

Tuberculosis

PPD, chest x-ray

Consider prophylaxis

Influenza

None

Vaccinate yearly

Pneumococcus

None

Vaccinate at least every 5 yr

HBV

HBsAg, HBsAb

Evaluate further if HBsAg positive, otherwise vaccinate to achieve and sustain a HBsAb response

HCV

HCV antibody

Evaluate further if HCV positive

CMV

CMV antibody

Post-transplant prophylaxis

EBV

EBV antibody

None

VZV

VZV

Vaccinate if antibody negative

Childhood infections

None

Measles, mumps, rubella, etc.

 

CMV, cytomegalovirus; EBV, Epstein-Barr virus; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; PPD, purified protein derivative; VZV, varicella zoster virus.

 

 

 

The history and physical examination should assess the patient's infection risk. A number of clinical conditions increase the chances of serious post-transplant infections, including: (1) prior splenectomy, (2) use of current or prior immunosuppressive or chemotherapeutic agents, (3) prior organ and/or bone marrow transplantation, (4) acquired or inherited immunodeficiency syndromes, (5) malnutrition, (6) the presence of open wounds or foreign bodies (including dialysis catheters), (7) poor dentition, (8) travel to areas endemic for specific infectious diseases, and (9) occupational exposure.[8]

Immunizations should be up to date. Patients should be immunized against childhood infections, [9] [10] influenza, pneumococcal infection, and hepatitis B. Asplenic patients should also be immunized against Haemophilus influenza and Meningococcus sp. Patients seronegative for Varicella zoster virus (VZV) infection should be immunized prior to transplantation. [11] [12] The VZV vaccine is a live-attenuated vaccine, and live vaccines should not be administered immediately before transplantation. Immunizations may be less effective in patients with stages 4 and 5 CKD, but there is little risk and potentially great benefit.

Patients with human immunodeficiency virus (HIV) infection may be transplant candidates if they (1) are adherent to a highly active antiretroviral therapy regimen, (2) have an undetectable virus load, (3) have a sustained CD4 lymphocyte count greater than 200/mL, (4) have no opportunistic infections, and (5) have no life-threatening malignancies.[13] Patients with HIV should be transplanted only in programs with appropriate expertise.

Tuberculosis remains a threat to kidney transplant recipients.[14] Tuberculosis may be difficult to diagnose in stage 5 CKD, owing to anergy to the purified protein derivative (PPD) skin test.[15] Patients who are PPD positive and have never been treated for tuberculosis should probably receive a 6-month course of prophylaxis with isoniazid. Therapy appears to be safe and possibly effective in both dialysis[16] and transplant patients.[17]

Malignancies

An active malignancy that is potentially life-threatening in an immunosuppressed patient is also a contraindication to transplantation. It can be questioned whether screening for cancer improves survival in a population at high risk for death from CVD and infections. [18] [19] However, there is also an obligation to not only protect the life of the transplant candidate but also to prevent transplanting a living or deceased donor kidney into a patient who succumbs prematurely to cancer. Therefore, it is generally recommended that transplant candidates undergo the same cancer screening that is recommended for the general population. This should include colonoscopy every 5 years for everyone over age 50. It should also include mammography for women over age 50 and younger women with a family history of breast cancer. Annual pelvic examination with cervical cytology testing is also recommended for women. Screening men over age 50 for prostate cancer with digital rectal examination and prostate-specific antigen testing is controversial. Screening for bladder cancer with cystoscopy may be beneficial in high-risk patients with analgesic nephropathy or chronic exposure to cyclophosphamide.

Patients with a history of prior malignancy are at increased risk for recurrence after transplantation. How long to wait before transplanting a patient with cancer that is in remission is always a difficult decision. However, based on tumor registry experience, rates of recurrence after variable disease-free intervals have led to some general recommendations for what may be a “safe” waiting period for specific tumor types ( Table 64-2 ).


TABLE 64-2   -- Disease-Free Intervals Recommended to Reduce the Chances of Malignancy Recurrence after Kidney Transplantation

Malignancy

Recommended Minimum Disease-Free Interval

Thyroid

2 yr

Testicular

2 yr

Cervical

2 yr

Breast—invasive

5 yr

Breast—ductal carcinoma in situ

2 yr

Colorectal carcinoma

5 yr

Colorectal carcinoma—localized

2 yr

Liver cancer

Avoid[*]

Leukemia

2 yr

Lymphoma

2 yr

Multiple myeloma

Avoid[†]

Lung cancer

2 yr

Prostate

2 yr

Prostate—focal disease only

None

Bladder—invasive

2 yr

Bladder—superficial

None

Renal cell—invasive

2 yr

Renal cell—incidental

None

Wilms' tumor

1 yr

Malignant melanoma

5 yr

Noninvasive skin cancers

None

 

*

Patients should probably not be transplanted unless it is in conjunction with liver transplantation.

Patients should probably not be transplanted unless it is in conjunction with bone marrow transplantation.

 

Cardiovascular Disease

CVD is the most common cause of death after kidney transplantation. However, it is not clear whether screening asymptomatic patients for CVD reduces morbidity and mortality. All patients should probably undergo a history, physical examination, electrocardiogram, and chest x-ray. Patients with symptomatic CVD should be assessed for possible intervention.

In most transplant programs, asymptomatic, high-risk patients, for example, patients with a history of CVD, diabetes, and/or multiple risk factors, undergo noninvasive cardiac stress testing.[20] Patients with a positive stress test are then subjected to angiography and revascularization of critical coronary lesions. Studies have shown that the risk of CVD events is low in low-risk patients, and screening such patients is not warranted. [21] [22] [23] However, screening high-risk pati-ents generally only results in revascularization in less than 10%, [21] [22] [23] and whether this low rate of revascularization can reduce CVD events can be questioned.

In a recent study, patients who were screened for CVD prior to elective peripheral vascular surgery, and were found to have significant coronary lesions, were randomized to revascularization or medical management.[24] Cardiac events were no different in the patients who underwent prophylactic revascularization compared with those who were managed medically. Although patients with CKD may be different from the patients in this study, the results nevertheless raise questions as to the effectiveness of screening prior to kidney transplantation.

Although the strength of the evidence has recently been questioned, a number of studies in the general population have shown that perioperative beta-blockade reduces cardiac events in high-risk patients.[25] Thus, it is reasonable to use beta-blocker therapy prior to kidney transplantation in patients with known CVD, diabetes, and/or multiple CVD risk factors. Patients with a history of a stroke or a transient ischemic attack (TIA) should be symptom free for at least 6 months before transplantation. Consideration should be given to using aspirin prophylaxis in patients with a history of thrombotic stroke or TIA[26] and, possibly, patients who are at high risk.[27] The risk of perioperative bleeding is generally outweighed by the benefits of aspirin prophylaxis in this setting.[28] Screening for asymptomatic carotid artery disease should be performed only in centers in which intervention with carotid endarterectomy and/or angioplasty can be done with minimal surgical complications. [29] [30]

Transplant candidates with a history of CVD, peripheral arterial disease (PAD), or claudication symptoms should be examined closely for signs of lower extremity arterial insufficiency. In addition, consideration should be given to ultrasound or magnetic resonance angiography to image the aorta and iliac arteries. Occasionally, occlusive arterial disease will restrict the placement of a kidney transplant, because of concerns either that the kidney will not receive sufficient blood flow or that the allograft may divert blood flow from an already compromised lower extremity.

Obesity

As the incidence of obesity has increased in the general population, the prevalence of obesity among patients referred for kidney transplantation has also risen. Obesity, that is, body mass index (BMI) of 30 kg/m2 or greater, is associated with a small, albeit statistically significant increase in the relative risks of death and graft failure. In addition, obese patients are at increased risk for wound dehiscence, wound infections, and other surgical complications. Obesity is also associated with increased blood pressure and a greater risk for developing diabetes mellitus after kidney transplantation.[31] Not surprisingly, the risks associated with obesity are proportional to the BMI.

Studies in the general population have shown that most obese patients can lose approximately 10% of their body weight in 6 months.[32] There are no studies of the safety and efficacy of weight reduction diets for patients with stage 5 CKD, however, it seems prudent to recommend weight loss for patients with BMI of 30 kg/m2 or higher and to insist on weight reduction for patients with BMI of 35 kg/m2 or higher. Although obesity should generally not be an absolute contraindication to transplantation, weight loss should probably be required for patients with BMI of 40 kg/m2 or higher. If diet is unsuccessful, bariatric surgery should be considered for patients with BMI ≤40 kg/m2 or higher.

Pulmonary Disease

Patients should be strongly encouraged to quit smoking prior to transplantation. Indeed, some would argue that patients should not be accepted for transplantation unless they can quit smoking. However, in the long run, this is difficult to enforce, and denying transplantation to people who smoke will preferentially deny transplantation to patients of lower socioeconomic status. Nevertheless, whenever possible, patients should be told to quit smoking and should be offered a formal smoking cessation program that includes nicotine replacement therapies.[33]

Patients who have a history of cigarette smoking and/or shortness of breath may benefit from pulmonary function testing and a chest x-ray. Rarely, patients with chronic lung disease may be at risk for postoperative pneumonia and ventilator dependence after transplant surgery.

Liver and Other Gastrointestinal Disorders

Transplant candidates should be screened for hepatitis B virus (HBV) replication with hepatitis B surface antigen (HBsAg), e-antigen, and viral load measured by polymerase chain reaction. If there is no evidence of HBV replication by these tests and HBV vaccine has been administered, then hepatitis B surface antibody (HBsAb) should be measured to determine if the HBV vaccine was effective. Alternatively, the HBV vaccine should be given and HBsAb response measured. Measuring hepatitis B core antibody (HBcAb) may be useful in determining whether there has been inactive, but relatively recent, HBV infection, in contrast to HbsAb, which generally indicates immunity conferred by vaccination.

Patients with evidence of HBV replication are high risk for chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. These risks may be aggravated by immunosuppression, and a liver biopsy is helpful in assessing the severity of liver disease. Patients with HBV replication should be treated with lamividine pre- and post-transplantation.[34] Alpha-interferon may also be used as an adjunct to lamividine pretransplant, but high doses are often poorly tolerated.

Hepatitis caused by the hepatitis C virus (HCV) is more common and more indolent than hepatitis caused by HBV. Nevertheless, HCV can cause severe liver disease and is associated with new-onset diabetes after kidney transplantation.[31] Transplant candidates should be screened with HCV antibody and, if positive, should have HCV RNA measured. Patients who are HCV RNA-positive should undergo biopsy, and treatment with ribavirin (with or without alpha-interferon) should be considered pretransplant.

Patients with HBV and/or HCV and chronic active hepatitis or cirrhosis are at high risk for developing hepatocelluar carcinoma and should have baseline and follow-up levels of alpha-fetoprotein. If liver disease is advanced, it may be best to forego kidney transplantation.

Transplant candidates with symptoms and/or a history of esophagitis, gastritis, or peptic ulcer disease may require endoscopy to rule out active disease, especially disease caused by infectious agents such as Candida sp. or Helicobacter pylori. Patients with asymptomatic gallstones generally do not require treatment before transplantation.

Recurrent Kidney Disease

As the incidence of early graft failure due to acute rejec-tion has declined, the incidence of late graft failure due to recurrent kidney disease has no doubt increased. Nevertheless, the incidence of graft failure due to recurrent disease is probably not high enough to preclude transplantation in most cases ( Table 64-3 ). An exception may be the patient who has quickly lost two or more grafts to recurrent idiopathic focal segmental glomerulosclerosis (FSGS). The chance of recurrence in patients who have already lost a graft to recurrent FSGS is at least 80%, and graft failure is common when this occurs. Conversely, proteinuria in some patients with recurrent FSGS may respond to plasma exchange, and it may be unwise to refuse transplantation to such patients.


TABLE 64-3   -- Chances of Kidney Disease Recurrence and Graft Failure if There is Recurrence of Kidney Disease

Primary Kidney Disease

Chances of Recurrence

Graft Failure if Recurrence

Idiopathic focal segmental glomerulosclerosis

30% (80% if prior graft loss due to recurrence)

50%

Type 1 MPGN

30% (80% if prior graft loss due to recurrence)

40%

Type 2 MPGN

100%

20%

Membranous glomerulonephritis

25%

50%

Immunoglobulin A (IgA) nephropathy

50%

25%

Hemolytic uremic syndrome (not diarrhea-associated)

30%

50%

Anti-glomerular basement membrane disease

15%

<5%

Diabetes

100%

20%

Systemic lupus erythematosus

10%

<5%

Vasculitis

25%

30%

Scleroderma

20%

50%

Amyloidosis

50%

?

Fabry's disease

100%

<5%

Primary oxalosis

90%–100%[*]

?

Cystinosis

0%

0%

 

MPGN, membranoproliferative glomerulonephritis.

 

*

Lower if the liver is also transplanted.

 

Histologic evidence of recurrent diabetic nephropathy can be found in virtually 100% of allografts. However, diabetic nephropathy is still an unusual cause of graft failure. A functioning pancreas transplant may slow the rate of progression of diabetic nephropathy[35]; however, by itself, this should not be enough reason to undergo pancreas transplantation.

Genitourinary Disorders

Patients who are asymptomatic and have no history of bladder dysfunction do not usually require further evaluation. Transplant candidates with a history of infections, bladder dysfunction, or analgesic nephropathy may benefit from a urologic evaluation to rule out cancer, obstruction, reflux, bladder stones, and chronic cystitis. It is important to have adequate urinary drainage established at the time of transplantation. This can usually be best accomplished with the patient's own bladder. Only occasionally is a urinary diversion necessary. When there is doubt, it may be best to proceed with transplantation and assume that the bladder will function adequately until proved otherwise.

Chronic Kidney Disease Management

Patients who are referred for transplant evaluation have stage 4 or 5 CKD. Anemia should be managed according to guidelines.[36] Similarly, it is important to maintain physiologic calcium, phosphorous, vitamin D, and parathyroid hormone levels. If on maintenance dialysis, the dialysis prescription should be adequate, and patients should not have a dialysis access infection or peritonitis (if being treated with chronic peritoneal dialysis) at the time of transplantation.

Thrombophilias

Approximately 2% of kidney allografts are lost to thrombosis. Many of these patients will have a predisposing coagulopathy.[37] Presumably, perioperative anticoagulation would prevent many of these graft thromboses. However, whether the risk:benefit ratio is high enough to warrant screening all patients is unclear, especially considering that screening is expensive, false positives may occur, and bleeding complications are not unusual. Needed is a randomized trial to determine whether screening is beneficial. Until then, the most prudent approach may be to screen patients with a history of venous thrombosis, including recurrent hemodialysis access thromboses with factor V Leiden, prothrombin G20210A mutation, and the presence of antiphospholipid antibodies.[37] If any of these are positive, perioperative anticoagulation could then be undertaken.

Noncompliance and Cognitive Impairment

Noncompliance with immunosuppressive medications is an all-too-common cause of kidney allograft failure. Unfortunately, predicting who will be noncompliant is often difficult, and most patients should be given the benefit of the doubt. Young age is one of the best predictors of medication noncompliance. Adolescents are especially loath to take immunosuppressive medications that change their personal appearance. However, such patients may eventually mature and become reliable transplant recipients. In general, most agree that patients with a history of blatant noncompliance need to demonstrate compliance with medications and the dialysis prescription for at least 6 months prior to acceptance for transplantation. Similarly, patients with a history of substance abuse need to undergo formal chemical dependency counseling and demonstrate that they are substance-free for at least 6 months before being accepted for transplantation.

Patients with cognitive impairment that is too severe to be certain that they will take their medications should probably not undergo transplantation. Conversely, mentally retarded patients living in a structured environment often do very well after kidney transplantation. In such cases, transplantation not only improves quality of life but also reduces the cost of ESRD care.

Immunologic Evaluation

Preformed antibodies to a donor kidney can be a major obstacle to transplantation. Patients acquire preformed antibodies to human tissues through (1) prior transplantations, (2) pregnancies, and (3) blood transfusions. The number of antibodies against potential donor antigens can be tested by measuring antibody-induced (complement-dependent) lysis of a panel of lymphocytes from different individuals in the population. The higher the panel reactive antibody (PRA; range 0%–100%) titer, the more difficult it will be to find a donor that the potential recipient will not reject with an antibody-mediated rejection.

The PRA is generally measured at the time of transplant evaluation and then periodically (usually quarterly) thereafter until transplantation. Often, the PRA will decline with time, especially if blood transfusions are avoided (through the use of iron and erythropoietin treatment of anemia). Nevertheless, a patient may also have an anamnestic anti-body response if re-exposed to an antigen, and it may be wise to avoid, if possible, transplantation with a donor antigen to which the recipient once had an antibody.

Human leukocyte antigens (HLAs) are also measured as part of the transplant evaluation. Graft survival is better the fewer mismatches (range 0-6) there are between the recipient and the donor. The number of mismatches is also used in the deceased donor organ allocation program in the United States. Donor kidneys with zero HLA mismatches are shared nationally, and about 15% to 20% of all deceased donor transplants in the United States are zero-mismatch kidneys. In addition, recipients with fewer HLA-D mismatches to a particular donor kidney are awarded points in the computer algorithm that allocates that kidney for transplantation.

Generally, the donor and the recipient must be blood group-compatible. However, some centers have been transplanting ABO-incompatible kidneys with good short-term outcomes. This has been accomplished by using additional measures to suppress antibody production in the recipient.

Whether a particular kidney can be transplanted is determined by a final cross-match that measures whether the recipient has an antibody to the donor kidney. If there is a positive cross-match owing to a low-titer antibody, some transplant centers will suppress the antibody with plasma exchange and/or intravenous immunoglobulin administration and will proceed with transplantation despite the positive cross-match. Few such centers have data on long-term outcomes for these cross-match-positive transplants.

FOLLOW-UP WHILE ON THE WAITING LIST

Patients who have a living donor can proceed directly to transplantation once the recipient and donor evaluations are completed. If there is no living donor, then patients are placed on the deceased donor waiting list. Depending on blood type, waiting times can be several years. Transplant candidates should be reassessed every 1 to 2 years while they are on the waiting list. For centers with large numbers of patients on the waiting list, this is difficult logistically. Therefore, some centers have adopted a strategy of assessing only transplant candidates who appear to have accrued enough waiting time to receive a kidney transplant in the near future. This strategy leaves vulnerable the small percentage of patients who may be transplanted at any time with a zero-HLA-mismatch kidney.

LIVING DONORS

A living donor transplant offers many advantages over that of a deceased donor transplant; both short- and long-term graft survival rates are better and exposure to dialysis is minimized. [38] [39] [40] Therefore, an increase in living donation in the United States has taken place. At least three other factors have contributed to this increase. First, outcome for recipients of living donor kidneys has improved steadily over the last 2 decades. Second, outcome for recipients of living unrelated donor kidneys is equivalent to that of recipients of non-HLA-identical living related donor kidneys.[41] Third, laparoscopic donor nephrectomy is now an option that is associated with less pain and a faster recovery for the donor than conventional open nephrectomy.[42]

Medical Evaluation of the Kidney Donor

The evaluation of candidates for kidney donation should minimize morbidity and mortality and at the same time maximize the quality of life for both the recipient and the donor. Every effort should be made to minimize the risk to the donor because this is an operation the donor does not need and is doing for altruistic reasons. Evaluation of the living kidney donor usually begins with education about the process and a screening history by the live donor coordinator who is typically a registered nurse. Prospective donors are then asked for a copy of their medical records, if available. Evaluating the donor's blood type is a first step because it determines compatibility with the recipient. If the initial information does not disclose an immediate contraindication to donation and the blood type is compatible, the donor is usually asked to undergo a thorough history and physical examination and a battery of tests to ensure the highest safety possible for the donor. This initial evaluation typically includes a complete blood count, a comprehensive metabolic panel, urine analysis, chest x-ray, electrocardiogram, and some form of cardiac evaluation for donors above the age of 55, which may include echocardiography or some form of stress testing, cross-matching, and finally, renal imaging. Concerning the latter, more centers are moving away from conventional angiography and are currently using computerized tomography or magnetic resonance angiography instead. In addition, most programs insist on the donor being evaluated by a social worker and occasionally a psychologist if there is any question about motive for donation. Perhaps the best source document outlining the routine screening for the potential living kidney donor comes from the Report of the Amsterdam Forum on the Care of the Living Kidney Donor.[43] The objective of this forum was to develop an international standard of care regarding living kidney donation. It was developed by a panel of experts from many countries and serves as an excellent resource for questions that routinely come up about kidney donation. The routine screening for kidney donors recommended by this forum is presented in Table 64-4 .


TABLE 64-4   -- Routine Screening for the Potential Living Kidney Donor

  

 

Urinalysis

  

 

Dipstick for protein, blood, and glucose

  

 

Microscopy, culture and sensitivity

  

 

Measurement of protein excretion rate

  

 

Assessment of renal function

  

 

Estimation/measurement of GFR

  

 

Blood tests

  

 

Hematologic profile

  

 

Complete blood count

  

 

Hemoglobinopathy (where indicated)

  

 

Coagulation screen (PT and APTT)

  

 

G6PD deficiency (where indicated)

  

 

Biochemical profile

  

 

Creatinine, urea, and electrolytes

  

 

Liver tests

  

 

Urate

  

 

Fasting plasma glucose

  

 

Bone profile

  

 

Glucose tolerance test (if fasting plasma glucose >6–7 mmol/L)

  

 

Blood lipids

  

 

Thyroid function tests (if indicated)

  

 

Pregnancy test (if indicated)

  

 

PSA (if indicated)

  

 

Virology and infection screen

  

 

Hepatitis B and C

  

 

Toxoplasma

  

 

Syphilis

  

 

HIV and HTLV 1, 2

  

 

Malaria (where indicated)

  

 

Cytomegalovirus

  

 

Trypanozome cruzi (where indicated)

  

 

Epstein-Barr virus

  

 

Schistosomiasis (where indicated)

  

 

HHV8 and HSV (where indicated)

  

 

Strongyloides (where indicated)

  

 

Typhoid (where indicated)

  

 

Brucellosis (where indicated)

  

 

Cardiorespiratory system

  

 

Chest x-ray

  

 

Electrocardiogram

  

 

Stress test

  

 

Echocardiography (where indicated)

  

 

Assessment of renal anatomy

  

 

Appropriate imaging investigations should allow confirmation of the presence of two kidneys of normal size and enable abnormalities of the collecting system and calcification or stone disease in the renal tract to be detected. They must also delineate the anatomy of the renal vasculature.

With permission from Delmonico F: Council of the Transplantation Society. A report of the Amsterdam Forum on the Care of the Live Kidney Donor: Data and medical guidelines. Transplantation 79:S53–S66, 2005.

APTT, activated partial thromboplastin time; GFR, glomerular filtration rate; G6PD, glucose-6-phosphate dehydrogenase; HHV, human herpes virus; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTLV, human T-cell lymphotropic virus; PSA, prostate-specific antigen; PT, prothrombin time.

 

 

 

 

Surgical Risk

As noted earlier, there has been a dramatic increase in the number of laparoscopic nephrectomies in kidney donors. Matas and co-workers[44] compared the living donor morbidity and mortality for open nephrectomy, hand-assisted laparoscopic nephrectomy, and non-hand-assisted laparoscopic nephrectomy. In a survey of 2828 living donor nephrectomies, 52.3% were open, 20.7% were hand-assisted, and 27% were non-hand-assisted. Two donors died from surgical complications and 1 was in a persistent vegetative state; all after laparoscopic nephrectomy. Reoperation was necessary in 0.4% of open cases, 1% of hand-assisted cases, and 0.9% of non-hand-assisted cases. Complications not requiring reoperations were reported for 0.3% of open cases, 1% of hand-assisted cases, and 0.8% in non-hand-assisted laparoscopic nephrectomy cases. Overall, readmission rate was higher for laparoscopic nephrectomy (1.6% vs. 6%), almost entirely as a result of an increase in gastrointestinal complications in laparoscopic nephrectomy donors. In summary, as the majority of transplant centers perform laparoscopic nephrectomy, it is reasonable to quote the previous numbers with the caveat that these numbers were early in the laparoscopic nephrectomy experience.

Assessment of Renal Function in Kidney Donors Pre-and Postdonation

Whereas the threshold glomerular filtration rate (GFR) accepted by most transplant physicians for living donors is 80 mL/min/1.73 m2, other centers may actually accept lower GFR ranges.[45] This GFR threshold is based on the evidence that there is a 2.28 relative risk of graft loss if donor GFR is less than 80 mL/min.[46] What continues to be a contentious issue is how kidney function should be measured. Whereas 24-hour urinary collection for creatinine clearance seems to be the most popular, its disadvantages and shortcomings are well known. There is a shift toward utilizing creatinine-based formulas, mainly the Cockcroft-Gault and the Modification of Diet in Renal Disease (MDRD) GFR estimating formulas. The utility of these formulas in kidney donors has been studied by Lin and associates[47] who assessed 117 potential kidney donors who underwent iothalamate or diethylenetriaminepenta-acetic acid (DTPA) GFR studies as part of the routine kidney donor evaluation. On average, the MDRD equations were more accurate and were within 30% and 50% of measured GFR more frequently than the Cockcroft-Gault formula. The MDRD equations consistently underestimated GFR, whereas the Cockcroft-Gault equation overestimated it. Therefore, these formulas are clearly insufficient in predicting GFR. This is of no surprise, especially in the case of the MDRD equation, which was developed in people with a GFR that is less than 60 mL/min. Therefore, formal GFR measurements should be done, especially when the Cockcroft-Gault, which typically overestimates GFR, is less than 80 mL/min. This finding was recently confirmed in people who have donated a kidney in the past. Ibrahim and colleagues[48] assessed the performance of the Cockcroft-Gault and MDRD formulas in 126 former kidney donors who were 12 ± 9 years after donation by comparing these formulas to iohexol GFR. Again, the MDRD eGFR underestimated GFR, and the Cockcroft-Gault overestimated it. Overall, the MDRD formula was more accurate and precise than the Cockcroft-Gault estimate, a finding analogous to the performance of these formulas in the predonation setting.

Consequences of Living with One Kidney

A major long-term concern regarding the use of living donors is whether unilateral nephrectomy predisposes to the development of kidney disease and premature death in the donor. Recent data regarding the latter concern suggest that kidney donors may actually live longer than the age-matched general population.[49] Uninephrectomy is followed by early compensatory changes; GFR and renal blood flow increase by 70% of prenephrectomy values within 7 days of donation. [50] [51] These compensatory hemodynamic changes, although initially beneficial, may ultimately prove deleterious. [52] [53] [54] In 1932, Chanutin and Ferris[52] demonstrated that rats survived after removal of one kidney and 50% to 70% of the contralateral kidney, but they quickly develop progressive azotemia. Hostetter and co-workers[55] studied renal structure and single-nephron GFR (SNGFR) 1 week after a one and one half renal ablation and concluded that hyperfiltration in the remaining nephron may prove maladaptive.[55] Both the glomerular structural changes and the increase in SNGFR can be prevented by decreasing the “work” of the remaining nephrons with protein restriction.[56] Rodent studies, however, required removal of one kidney plus significant damage to, or removal of a large portion of, the remaining kidney before progressive renal insufficiency ensued. The rat differs from many other species in that its lifespan is shorter and an age-related progressive glomerulosclerosis is routinely observed in laboratory rats. [57] [58] Moreover, subtotal nephrectomy in other species does not uniformly lead to the same progressive loss of renal function. [57] [58] [59] [60]

If more than half of the renal mass needs to be removed in the rat before compensatory changes lead to renal insufficiency, why should donor nephrectomy be a concern? One needs to seriously consider the possibility that “hyperfiltration damage” may be additive to the background of the “normal” loss of kidney function with age. Numerous, but not all, cross-sectional studies in healthy humans have shown an age-related decrease in GFR.[61]Histologic studies have also shown that after the 4th decade of life, the incidence of sclerotic glomeruli increases in otherwise healthy males.[62] Moreover, Striker and associates[53] noted that when unilateral nephrectomy is performed in older rats, glomerulosclerosis was more prominent in the remaining kidney. Brenner and colleagues[56] suggest that “age-related glomerulosclerosis poses no threat to well-being. If, however, extrinsic renal disease or surgical loss of renal tissue adds to the glomerular burden imposed by eating ad libitum, the course of glomerulosclerosis may be hastened considerably.”

In humans, evidence that a reduction in renal mass may lead to progressive renal failure comes from studies of children born with a reduced number of functioning nephrons and reports of focal sclerosis developing in patients with unilateral renal agenesis. [63] [64] [65] [66] Of more relevance to living donors, Anderson and co-workers[67] compared the survival rates of 232 patients who underwent nephrectomy for benign disease with the overall Danish population. If the remaining kidney was normal, survival was identical to that of the overall population. Zucchelli and associates[68] reported that during the follow-up of 3 to 37 years, 7 of 24 patients who had undergone unilateral nephrectomy and who had a normal remaining kidney by intravenous pyelography developed proteinuria. In 4 of these patients, kidney biopsy showed focal and segmental glomerulosclerosis. Proteinuria developed, on average, in 12.2 years after nephrectomy. After development of proteinuria, it had not increased further, and renal function, as measured at least by serum creatinine, remained stable. Other long-term follow-up studies after nephrectomy performed for unilateral disease have not shown progressive deterioration in renal function. [69] [70] Narkun-Burgess and colleagues[70] assessed 56 World War II veterans who lost a kidney to trauma during the war (follow-up 45 yr) and compared them with other World War II veterans of the same age. Mortality was not increased in those who had lost a kidney, and none of the 28 living veterans (average age 64.4 yr; average interval after kidney loss 45.1 yr) had serious renal insufficiency. Other similar studies, albeit with shorter follow-up, have noted small increases in blood pressure and an increased incidence of mild proteinuria after uninephrectomy. Of particular interest in humans are the case reports of patients with partial loss of a solitary kidney. Of 35 such patients studied, 31 were reported to have stable renal function. [71] [72] [73] Novick and co-workers[73] evaluated 14 patients who were 5 to 17 years after partial nephrectomy of a solitary kidney: 12 had stable renal function but 2 developed renal failure and 9 had proteinuria. The extent of proteinuria correlated directly with the length of follow-up and inversely with the amount of remaining renal tissue. Isolated cases of renal failure after donor nephrectomy have been reported. [74] [75] No large series, however, has demonstrated any evidence of progressive deterioration of renal function in kidney donors. In recognition of this benign course, insurance companies do not increase premiums for kidney donors.

In 1991, Najarian and associates[76] studied donors 20 years or longer after donation (range 21-29) by comparing their renal function, blood pressure, and proteinuria with their siblings. Of 130 donors between January 1963 and December 1970, 125 were located; these were sent questionnaires about their current health and a request to participate in a follow-up study. Of these 125, 78 donors or donor families returned the questionnaire. Of the remaining 47, 32 were known to be alive but did not respond. In addition, for each donor, all siblings were asked to participate. Fifteen donors had died, 2 to 25 years postdonation; none of the 15 had kidney disease at death. In the 57 donors, mean serum creatinine was 1.1 ± 01 mg/dL and blood pressure was 134 ± 2/80 ± 1 mm Hg. Thirty-two percent of the donors were taking antihypertensive drugs and 23% had proteinuria. The 65 siblings did not differ from the donors in either their demographics or outcomes of interest; mean serum creatinine level 1.1 ± 0.03 mg/dL and blood pressure 130 ± 3/80 ± 1.5 mm Hg. Recently, the same group studied all donors 20 years after donation.[77] Information on 464 (60%) of the 773 donors was obtained. Of the 464 donors, 84 had died. The cause of death was available for 27: 24 had no kidney disease, but 3 were on dialysis at the time of death. Of these 3 who died with kidney failure, 1 developed diabetes and diabetic nephropathy and started dialysis 10 years after donating a kidney and partial pancreas; 1 developed kidney failure secondary to hemolytic uremic syndrome at age 76 (32 yr postdonation); and 1 had prerenal failure secondary to cardiac disease. In all, 380 of the kidney donors were known to be alive more than 20 years after donation. Most recently and utilizing measured GFR, Ibrahim and colleagues[78] compared former donors to the Third National Health and Nutrition Examination Survey (NHANES III) data and found the overwhelming majority of donors; 87%, had an estimated GFR greater than 60 mL/min/1.73 m2. The presence of hypertension but not diabetes nor time from donation were independent risk factors for having a higher CKD stage.[78]

Postdonation Development of Diabetes and Risk of Nephropathy

It is unknown whether or not having diabetes with a single functioning kidney results in significant functional and structural differences compared with having diabetes and two functional kidneys. Mauer and colleagues have examined clinical and morphologic differences between kidney biopsies from diabetic renal transplant subjects and subjects with diabetes and two functioning kidneys (personal communication). They found a small decrease in the surface volume of the peripheral glomerular basement membrane per glomerulus in subjects with one kidney compared with subjects with two kidneys, and both groups with diabetes had lower values than in the control subjects. There was no difference in the mesangial matrix volume of subjects with one kidney compared with those with two kidneys; both groups had increased mesangial volume compared with biopsies from a control population without diabetes. Clinically, albumin excretion rate, serum creatinine, and systolic blood pressure were slightly greater in subjects with diabetes and one kidney compared with those with two kidneys. The subjects with one functioning kidney also had a higher GFR. Twenty-three of the subjects with diabetes and one kidney had hypertension compared with 5 subjects in the two-kidneys group. These data do not demonstrate lesions consistent with a progressive diabetic nephropathic process in the subjects with diabetes and one kidney compared with those with two kidneys.

It has been noted that in nine diabetic patients with either unilateral agenesis or unilateral nephrectomy, none suffered accelerated kidney failure in the remaining kidney. [79] [80] In contrast, data from Silveiro and co-workers[81]compared single-and two-kidney patients with diabetes who were gender- and BMI-matched. In total, diabetics with normal renal function who underwent nephrectomy do well in the short term. They do, however, have a higher prevalence of retinopathy, neuropathy, and macrovascular diseases in addition to increasing proteinuria with longer follow-up. In general, individuals who are at risk for developing type 2 diabetes (positive family history, BMI >30 kg/m2, history of gestational diabetes, and excessive alcohol use) should be counseled about the 30% risk of developing type 2 diabetes if the offspring of a diabetic, should lose weight, and should reduce alcohol intake. Screening with a 2-hr glucose tolerance test in high-risk donors is routine in most centers. Applying a predication model that was developed by Haffner and associates[82] is an alternative.

Does Donation Place the Kidney Donor at Higher Cardiovascular Risk?

A number of reports indicate that elevated serum creatinine may be an independent predictor of all-cause and CVD mortality. These studies, however, have focused on specific groups such as hypertensive individuals, elderly, patients with recent stroke, survivors of myocardial infarction, patients undergoing carotid end-arterectomy elective cardiac valve surgery, and patients with left ventricular systolic dysfunction. A more contemporary study addressing the link between depression in kidney function and the risk of CVD in community-based population was published by Manjunath and colleagues[83] regarding the risk of cardiovascular disease in the Atherosclerosis Risk in Community (ARIC). After a mean follow-up of 6.2 years, subjects with GFR of 15 to 59 mL/min had a hazard ratio of 1.38 and those with a GFR between 60 and 89 mL/min had a hazard ratio of 1.16 for atherosclerotic CVD compared with subjects with a GFR of 90 to 150 mL/min. Go and co-workers[84] estimated the longitudinal GFR among 1,120,295 adults in whom serum creatinine was measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. After a median follow-up of 2.8 years, the adjusted hazard ratio for death was 1.2 for those with a GFR of 45 to 59 mL/min and 5.9 for those with an eGFR of less than 15 mL/min. The adjusted hazard ratio for cardiovascular events also increased inversely with eGFR. Similar findings were also reproduced by Foley and colleagues[85] in their study of a 5% sample of the U.S. Medicare population in 1998 and 1999. Whether the presence of reduced renal function without the coexistence of other traditional risk factors for CVD places kidney donors at higher risk is unknown and will be difficult to study unless a national registry of kidney donors is created.

Special Donor Situations

Obesity

Obesity is a worldwide public health problem. In addition to the adverse impact obesity has on a multitude of health outcomes, it is now well appreciated that individuals afflicted with this condition are more prone to develop functional and structural changes in the kidneys.[86] Of greatest significance is the observation that obesity may lead to a marked increase in the GFR, higher likelihood of systemic hypertension, and proteinuria. Whereas the exact prevalence of glomerular lesions in obese individuals is unknown, data from Kambham and associates[87] suggest that glomerular enlargement with or without FSGS may have increased in the last 15 years. In addition to the observed hyperfiltration, it has been shown that obese animals have an increased expression of transforming growth factor-β (TGF-β), a cytokine that has been linked to the development of kidney disease. More recently, Sibley and colleagues[88] demonstrated a relationship between visceral adiposity and circulating and urinary TGF-β levels. These concerns in conjunction with the concerns about the surgical risk for obese donors have generally precluded at least the severest of cases from becoming kidney donors. More recently, however, Heimbach and co-workers[89] demonstrated laparoscopic donor nephrectomy to be generally safe in selected obese donors and demonstrated no difference in renal function or the prevalence of albuminuria 6 to 12 months in those with BMI more than 35 versus those with a BMI of less than 25.[89]

Whereas it has been long accepted that obesity might lead to proteinuria and worsening hypertension, the development of more advanced kidney dysfunction has not been demonstrated until recently.[90] Hsu and colleagues,[90] in a study of over 320,000 adult members of Kaiser Permanente who volunteered for screening health check-ups between 1964 and 1985, demonstrated over a 700% increase in the adjusted risk of ESRD in subjects with a BMI greater than 40 ( Table 64-5 ). Even more disturbing is the emerging link between obesity and the development of renal cell carcinoma, especially in women.[91]


TABLE 64-5   -- Obesity and Risk of End-Stage Renal Disease[*]

BMI (kg/m2)

Adjusted RR of ESRD

<18.5

0.44

18.5–24.9

1.0

25.0–29.9

1.87

30.0–34.9

3.57

35.0–39.9

6.12

>40.0

7.07

From Hsu C, McCulloch C, Iribarren C, et al: Body mass index and risk of end stage renal disease. Ann Intern Med 144(1):21–28, 2006.

BMI, body mass index; ESRD, end-stage renal disease; RR, risk ratio.

 

*

Model adjusted for Multiphasic Health Checkup period, age, sex, race, education level, smoking status, history of myocardial infarction, serum cholesterol level, proteinuria, and serum creatinine level.

 

 

In summary, there is evidence that obesity, in addition to its cosegregation with other known risk factors for the development of kidney disease, namely hypertension and diabetes, may lead to the development of ESRD, and while the surgical aspects of obese donors may have become more acceptable, most centers continue to exclude kidney donors with BMI greater than 35 until they have actually lost the weight.

Hypertension

There is less doubt that hypertension is an independent risk factor for ESRD. What is even more sobering are the recent demonstrations that blood pressure that is well within the normal range can be associated with CVD. These observations have generally resulted in excluding hypertensive subjects from becoming kidney donors, although some programs will allow a hypertensive donor whose blood pressure is well controlled. Probably the best available data regarding the outcome of hypertensive kidney donors come from Textor and co-workers.[92] Out of 148 consecutive living kidney donor candidates who underwent donor nephrectomy between January 2001 and December 2002, 24 subjects were found to be hypertensive. After roughly 10 months of follow-up, normotensive donors had no change in awake ambulatory blood pressure whereas the blood pressure in the hypertensive donors actually fell with both nonpharmocologic and drug therapy by at least 10 mm Hg for the systolic and 5 mm Hg for the diastolic blood pressure. Whereas the hypertensive donors started at a lower GFR at the time of donation, after adjustment for age, there was no independent blood pressure effect for predicting GFR either before or after nephrectomy. Most assuring was the demonstration that there was no difference in urinary protein in these hypertensive donors. Although these results are encouraging, one has to remember that this is a highly selected population of subjects who were not microalbuminuric, had a normal GFR, and had modestly severe hypertension.

The physician is not uncommonly faced with a situation in which a subject's blood pressure is elevated during the clinic visit. Observations from the same group that have accepted hypertensive donors have demonstrated that home blood pressure and 24-hour ambulatory blood pressure readings are comparable in their ability to detect hypertension. Only office blood pressure was disconcordant.

Recommendations from the Amsterdam Forum on the Care of the Live Kidney Donor[43] regarding hypertension in the donors are (1) patients with a blood pressure higher than 140/90 mm Hg by ambulatory blood pressure should generally not be accepted as donors and (2) the preferred method of measurement is ambulatory blood pressure monitoring particularly in those above age 55 and those with high office blood pressure readings. For those with easily controlled hypertension, age must be above 50, GFR should be 80 mL/min or higher, and normoalbuminuric. Donors with hypertension should be regularly followed up by a physician.

Nephrolithiasis

It is generally accepted that subjects with nephrocalcinosis on a plain x-ray of the abdomen, especially when bilateral in nature, those with kidney stones that are known to have high recurrence rates such as cystine stones, infection stones, primary hyperoxaluria, and those with renal tubular acidosis or inflammatory bowel disease should be excluded from donation. Whether one should accept those with a history of a single kidney stone remains debatable but those with a favorable urine profile, namely the absence of hypercalciuria, oxaluria, or recurrent urinary tract infections, should probably be allowed to donate. If a kidney donor is found to have an asymptomatic stone during the evaluation and has a favorable urine profile, he or she can probably donate as long as the size of the stone is less than 15 mm or potentially removable during transplant. Whether a stent should be placed in the recipient of the kidney with the stone is not agreed upon.

Malignancy

As part of the living donor thorough medical evaluation, basic screening for malignancy should be done. This includes chest x-ray and flexible sigmoidoscopy plus hemoccult screening or colonoscopy for those above 50. A mammogram (>35 yr) and a pelvic examination for females above the age of 20 should also be done.

Potential donors who have a history of renal cell carcinoma, choriocarcinoma, lymphomas and leukemias, lung and breast cancer, testicular cancer, and monoclonal gammopathy should be excluded from donation. In regard to those with remote history of malignancy, the Amsterdam Forum considers them acceptable candidates if prior treatment and the malignancy itself do not decrease renal mass or put the donor at increased risk for ESRD and that the prior treatment does not increase the operative risk for nephrectomy.

Infectious Diseases

Donors should be screened carefully for active infections by a careful history, physical examination, chest x-ray, and complete blood count. A more detailed and targeted approach should be employed for the potential donor with a suspicion for a certain infection. Probably, the most comprehensive recommendations regarding infection in the kidney donor comes from the Report of the Amsterdam Forum on the Care of the Live Kidney Donor.[43] Their recommendations are summarized in the Table 64-6 .


TABLE 64-6   -- Screening for Infectious Diseases in the Donor

Infection

Recommendation

HIV

A positive HIV-1, HIV-2 by ELISA should be confirmed by Western blot analysis. A positive test excludes the donor.

HTLV-1

Endemic in the West Indies and Japan.

 

Causative agent for T-cell leukemia and spastic paraparesis (HTLV-1).

 

HTLV-2 is seen in IV drug users and risk of infection is unknown.

CMV/EBV

Donors with positive IgM and PCR for CMV cannot donate until their PCR is negative.

 

It is preferable, if feasible, for a donor who is positive for both CMV/EBV to donate to a child who is positive because PTLD is a major issue in seronegative children receiving organs from seropositive adults.

HCV

HCV positive with normal or elevated liver enzymes donors should be excluded if the recipient is HCV negative.

 

HCV-positive donors wishing to donate to HCV-positive recipients should have quantitative PCR measured. If positive by PCR, they should be excluded. If PCR is negative, they may still donate because the kidney is not a known reservoir for HCV.

 

Genotyping HCV-positive donor and recipient should be done.

 

Previously treated HCV donors, especially those with favorable genotypes, can be considered as donors.

HBV

HBsAg positivity generally excludes the donor.

 

Donors who are IgM core-positive can be considered later to determine whether the infection is progressive.

HSV-8

There is no routine screening and is currently not recommended.

TB

TB may remain dormant in the kidney and, therefore, is a contraindication to donation.

 

PPD skin test is not universally practiced.

 

Active TB is a contraindication to donation.

 

Donors with a past history of TB may be considered, especially if they were treated and have extensive evaluation for genitourinary TB.

Syphilis

All donors should be screened with RPR or VDRL. Positive tests should be confirmed by FTA absorption test.

 

FTA-positive donors should be treated before donation according to the stage of their disease.

Chagas' disease

Endemic in Central and South America and Mexico.

 

Donors from endemic areas should be screened by serologic tests.

 

Donors with positive serology should not be excluded unless the xenodiagnostic blood test is positive.

 

Recipients of a kidney from Chagas'-seropositive donors can be safely transplanted especially if treated with benznidazole for 2 wk.

Schistosomiasis

Uncomplicated schistosomiasis does not adversely affect kidney function.

 

Only symptomatic donors should be treated before donation for 1 mo with praziquantel and oxamniquine.

Strongyloides

Because strongyloides has been transmitted via a kidney transplant, screening is recommended in endemic areas.

Brucellosis

Donors treated in the past for brucellosis should not be excluded.

Malaria

Those who reside in or have traveled to endemic areas should be screened.

 

Malaria has been transmitted from an organ donor to multiple transplant recipients.

Urinary tract infection

Unexplained recurrent pyelonephritis is a contraindication to donation but recurrent cystitis is not.

 

Potential donors with recurrent infection may require a VCUG.

Adapted from Delmonico F: Council of the Transplatation Society. A report of the Amsterdam Forum on the Care of the Live Kidney Donor: Data and medical guidelines. Transplantation 79:S53–S66, 2005.

CMV, cytomegalovirus; EBV, Epstein-Barr virus; ELISA, enzyme-linked immunosorbent assay; FTA, fluorescein treponemal antibody; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HSV, herpes simplex virus; HTLV, human T-cell lymphotropic virus; IgM, immunoglobulin M; PCR, polymerase chain reaction; PPD, purified protein derivative; PTLD, post-transplantation lymphoproliferative disorder; RPR, rapid plasma regain; TB, tuberculosis; VCUG, voiding cystourethrogram; VDRL, Venereal Disease Research Laboratory.

 

 

 

 

Hematuria

The evaluation of microscopic hematuria in a potential donor should be similar to that used in the general population. Routine screening with standard reagent strips commonly produces false positives, but false negatives are infrequent. Therefore, a negative result is quite reliable, whereas a positive result should be confirmed by examining the urine sediment. Hematuria combined with proteinuria, cellular casts, renal insufficiency, or hypertension is suggestive of glomerular disease, although the absence of these signs does not rule out glomerular disease.

Epidemiologic screening studies demonstrate isolated, transient microscopic hematuria in up to 35% of young men and up to 13% of postmenopausal women. Often, no etiology is found in younger individuals. The literature supports noninvasive monitoring and follow-up of young individuals with isolated microscopic hematuria, given the low risk for malignancy if ultrasound or intravenous pyelogram is normal. Renal biopsy and cystoscopy are usually not necessary. The situation is somewhat different in the older individual (>40–50 yr) with hematuria, because there is a greater chance of malignancy. Individuals over 40 to 50 years of age require periodic follow-up with urinary cytology and possibly repeat cystoscopy and radiograpic examinations.[93]

Persistent microscopic hematuria (defined as >3 months' duration) is seen in up to 3% of the general population and is more likely to be associated with pathologic findings. In a study of 512 consecutive prospective donors, Koushik and associates[94] noted that 14 (2.7%) continued to have asymptomatic, microscopic hematuria over 1 month. If the medical history, physical examination, and computed tomographic angiography were unremarkable, and if they still wished to donate, a kidney biopsy was performed. In 2 prospective donors, hematuria resolved after treatment for urinary tract infection; 2 others declined donation and were referred to their primary care provider. Kidney biopsy in the remaining 10 showed 2 normal; 4 thin basement membrane nephropathies; 1 nonhomogeneous basement membrane abnormalities; 1 immunoglobulin A (IgA) nephropathy; 5 of 16 glomeruli globally sclerotic; 1 in a patient with a family history of Schimke's syndrome, 7 of 30 glomeruli globally sclerotic; and one thin basement membrane nephropathy and early hypertensive changes without systemic hypertension. Only 4 of the 10 who underwent kidney biopsy donated (2 normal, 2 thin basement membrane disease).

Pregnancy after Kidney Donation

There is no evidence that the rise in GFR seen with pregnancy and after uninephrectomy adversely affect maternal or infant health. It is preferable that pregnancy be postponed until at least 2 months after donation to assess renal compensation before conception.[43]

Coagulation Abnormalities

Generally, prothrombin time, partial thromboplastin time, and platelets counts are sufficient. If there is a prior history of venous thrombosis, especially one without an identifiable predisposition (i.e., previous surgery), the donor should be evaluated by a hematologist.

Smoking

The adverse impact of smoking on a multitude of health aspects is well established. Of more relevance to kidney donors is the repeated and very strong association between smoking and renal cell carcinoma. [91] [95] As a matter of fact, the relative risk of renal cancer in those who ever smoked to those who never smokes was 1.38 (95% confidence interval = 1.09–1.36). This association was seen in both men and women.[95] Moreover, smoking is associated with increased risk for the development of CKD. [96] [97] In a community-based prospective observational study of 20-year duration, of 23,534 subjects, Haroun and colleagues[97] demonstrated a 2.4 and a 2.9 relative risk for smoking in the development of ESRD in men and women, respectively.[97] Whereas the mechanism by which smoking may lead to CKD is unknown, it has been proposed that acute hemodynamic changes, rise in systemic and intraglomerular pressure, and the chronic effects causing endothelial dysfunction may be responsible.[98] Based on this information, donors should be strongly discouraged from smoking and should receive formal counseling regarding smoking cessation especially prior to the date of surgery.

CONCLUSION

Living kidney donation constitutes the best renal replacement therapy option for most patients with ESRD. Every effort should be made to protect kidney donors and ensure that their motive for donation is truly altruistic. The establishment of national donor registries is greatly needed to answer many remaining questions regarding the long-term renal and nonrenal consequences of reduced renal mass.

References

1. Wolfe RA, Ashby VB, Milford EL, et al: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.  N Engl J Med  1999; 341(23):1725-1730.

2. Kasiske BL, Ramos EL, Gaston RS, et al: The evaluation of renal transplant candidates: Clinical practice guidelines.  J Am Soc Nephrol  1995; 6(1):1-34.

3. Kasiske BL, Cangro CB, Hariharan S, et al: The evaluation of renal transplantation candidates: Clinical practice guidelines.  Am J Transplant  2001; 1(suppl 2):3-95.

4. European Best Practice Guideines Expert Group on Renal Transplantation : Section I: Evaluation, selection and preparartion of the potential transplant recipient.  Nephrol Dial Transplant  2000; 15(suppl 7):3-38.

5. Knoll G, Cockfield S, Blydt-Hansen T, et al: Canadian Society of Transplantation: Consensus guidelines on eligibility for kidney transplantation.  CMAJ  2005; 173(10):S1-S25.

6. Kasiske BL, Snyder JJ, Matas AJ, et al: Preemptive kidney transplantation: The advantage and the advantaged.  J Am Soc Nephrol  2002; 13(5):1358-1364.

7. Kasiske BL, Snyder J: Matching older kidneys with older patients does not improve allograft survival.  J Am Soc Nephrol  2002; 13(4):1067-1072.

8. Green M, Avery RK, Preiksaitis J (ed): Guidelines for the prevention and management of infectious complications of solid organ transplantation . Am J Transplant  2004; 4(suppl 10):4-166.

9. Watson JC, Hadler SC, Dykewicz CA, et al: Measles, mumps, and rubella—Vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: Recommendations of the Advisory Committee on Immunization Practices (ACIP).  MMWR Recomm Rep  1998; 47(RR-8):1-57.

10. Atkinson WL, Pickering LK, Schwartz B, et al: General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP).  MMWR Recomm Rep  2002; 51(RR-2):1-35.

11. Broyer M, Tete MJ, Guest G, et al: Varicella and zoster in children after kidney transplantation: Long-term results of vaccination.  Pediatrics  1997; 99(1):35-39.

12. Olson AD, Shope TC, Flynn JT: Pretransplant varicella vaccination is cost-effective in pediatric renal transplantation.  Pediatr Transplant  2001; 5(1):44-50.

13. Stock PG, Roland ME, Carlson L, et al: Kidney and liver transplantation in human immunodeficiency virus-infected patients: A pilot safety and efficacy study.  Transplantation  2003; 76(2):370-375.

14. Klote MM, Agodoa LY, Abbott K: Mycobacterium tuberculosis infection incidence in hospitalized renal transplant patients in the United States, 1998-2000.  Am J Transplant  2004; 4(9):1523-1528.

15. Woeltje KF, Mathew A, Rothstein M, et al: Tuberculosis infection and anergy in hemodialysis patients.  Am J Kidney Dis  1998; 31(5):848-852.

16. Vikrant S, Agarwal SK, Gupta S, et al: Prospective randomized control trial of isoniazid chemoprophylaxis during renal replacement therapy.  Transpl Infect Dis  2005; 7(3-4):99-108.

17. Agarwal SK, Gupta S, Dash SC, et al: Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient.  Int Urol Nephrol  2004; 36(3):425-431.

18. Chertow GM, Paltiel AD, Owen Jr WF, Lazarus JM: Cost-effectiveness of cancer screening in end-stage renal disease.  Arch Intern Med  1996; 156(12):1345-1350.

19. Kiberd BA, Keough-Ryan T, Clase CM: Screening for prostate, breast and colorectal cancer in renal transplant recipients.  Am J Transplant  2003; 3(5):619-625.

20. Danovitch GM, Hariharan S, Pirsch JD, et al: Management of the waiting list for cadaveric kidney transplants: Report of a survey and recommendations by the Clinical Practice Guidelines Committee of the American Society of Transplantation.  J Am Soc Nephrol  2002; 13(2):528-535.

21. Lewis MS, Wilson RA, Walker KW, et al: Validation of an algorithm for predicting cardiac events in renal transplant candidates.  Am J Cardiol  2002; 89(7):847-850.

22. Patel AD, Abo-Auda WS, Davis JM, et al: Prognostic value of myocardial perfusion imaging in predicting outcome after renal transplantation.  Am J Cardiol  2003; 92(2):146-151.

23. Kasiske BL, Malik MA, Herzog CA: Risk-stratified screening for ischemic heart disease in kidney transplant candidates.  Transplantation  2005; 80(6):815-820.

24. McFalls EO, Ward HB, Moritz TE, et al: Coronary-artery revascularization before elective major vascular surgery.  N Engl J Med  2004; 351(27):2795-2804.

25. Devereaux PJ, Beattie WS, Choi PT, et al: How strong is the evidence for the use of perioperative beta blockers in non-cardiac surgery? Systematic review and meta-analysis of randomised controlled trials.  BMJ  2005; 331(7512):313-321.

26. Weisman SM, Graham DY: Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events.  Arch Intern Med  2002; 162(19):2197-2202.

27. Berger JS, Roncaglioni MC, Avanzini F, et al: Aspirin for the primary prevention of cardiovascular events in women and men: A sex-specific meta-analysis of randomized controlled trials.  JAMA  2006; 295(3):306-313.

28. Burger W, Chemnitius JM, Kneissl GD, Rucker G: Low-dose aspirin for secondary cardiovascular prevention—Cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation—Review and meta-analysis.  J Intern Med  2005; 257(5):399-414.

29. Biller J, Feinberg WM, Castaldo JE, et al: Guidelines for carotid endarterectomy: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association.  Stroke  1998; 29(2):554-562.

30. Bettmann MA, Katzen BT, Whisnant J, et al: Carotid stenting and angioplasty: A statement for healthcare professionals from the Councils on Cardiovascular Radiology, Stroke, Cardio-Thoracic and Vascular Surgery, Epidemiology and Prevention, and Clinical Cardiology, American Heart Association.  Stroke  1998; 29(1):336-338.

31. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ: Diabetes mellitus after kidney transplantation in the United States.  Am J Transplant  2003; 3(2):178-185.

32. Snow V, Barry P, Fitterman N, et al: Pharmacologic and surgical management of obesity in primary care: A clinical practice guideline from the American College of Physicians.  Ann Intern Med  2005; 142(7):525-531.

33. A clinical practice guideline for treating tobacco use and dependence: A US Public Health Service report. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives.  JAMA  2000; 283(24):3244-3254.

34. Gane E, Pilmore H: Management of chronic viral hepatitis before and after renal transplantation.  Transplantation  2002; 74(4):427-437.

35. Fioretto P, Steffes MW, Sutherland DER, et al: Reversal of lesions of diabetic nephropathy after pancreas transplantation.  N Engl J Med  1998; 339:69-75.

36. IV. NKF-K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease: update 2000.  Am J Kidney Dis  2001; 37(1 suppl 1):S182-S238.

37. Irish A: Hypercoagulability in renal transplant recipients. Identifying patients at risk of renal allograft thrombosis and evaluating strategies for prevention.  Am J Cardiovasc Drugs  2004; 4(3):139-149.

38. Cosio FG, Alamir A, Yim S, et al: Patient survival after renal transplantation: I. The impact of dialysis pre-transplant.  Kidney Int  1998; 53:767-772.

39. Meier-Kriesche H-U, Port FK, Ojo AO, et al: Effect of waiting time on renal transplant outcome.  Kidney Int  2000; 58:1311-1317.

40. Papalois VE, Moss A, Gillingham KJ, et al: Pre-emptive transplants for patients with renal failure, an argument against waiting until dialysis.  Transplantation  2000; 70:625-631.

41. Gjertson DW, Cecka JM: Living unrelated donor kidney transplantation.  Kidney Int  2000; 58:491-499.

42. Wolf Jr JS, Merion RM, Leichtman AB, et al: Randomized controlled trial of hand-assisted laparoscopic versus open surgical live donor nephrectomy.  Transplantation  2001; 72(2):284-290.

43. Delmonico F: Council of the Transplantation Society. A report of the Amsterdam Forum on the Care of the Live Kidney Donor: Data and medical guidelines.  Transplantation  2005; 79:S53-S66.

44. Matas AJ, Bartlett AT, Leichtman AB, Delmonico FL: Morbidity and mortality after living kidney donation in 1999-2001: A survey of United States transplant centers.  Am J Transplant  2003; 3(7):830-834.

45. Davis C: Evaluation of the living kidney donor: Current perspectives.  Am J Kidney Dis  2004; 43(3):508-530.

46. Norden G, Lennerling A, Nyberg G: Low absolute glomerular filtration rate in the living kidney donor: A risk factor for graft loss.  Transplantation  2000; 70:1360.

47. Lin J, Knight E, Hogan M, Singh A: A comparison of predication equations for stimulating glomerular filtration rate in adults without kidney disease.  J Am Soc Nephrol  2003; 14:2573-2580.

48. Ibrahim H, Rogers T, Tello A, Matas A: The performance of three serum creatinine based formulas in estimating GFR in former kidney donors.  Am J Transplant  2006; 6:1479-1485.

49. Fehrman-Ekholm I, Elinder CG, Stenbeck M, et al: Kidney donors live longer.  Transplantation  1997; 64(7):976-978.

50. Ogden DA: Consequences of renal donation in man.  Am J Kidney Dis  1983; 2(5):501-511.

51. Donadio Jr JV, Farmer CD, Hunt JC, et al: Renal function in donors and recipients of renal allotransplantation. Radioisotopic measurements.  Ann Intern Med  1967; 66(1):105-115.

52. Chanutin A, Ferris EG: Experimental renal insufficiency produced by partial nephrectomy.  Arch Intern Med  1932; 49:767.

53. Striker GE, Nagle RB, Kohnen PW, Smuckler EA: Response to unilateral nephrectomy in old rats.  Arch Pathol  1969; 87(4):439-442.

54. Shimamura T, Morrison AB: A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats.  Am J Pathol  1975; 79(1):95-106.

55. Hostetter TH, Olson JL, Rennke HG, et al: Hyperfiltration in remnant nephrons: A potentially adverse response to renal ablation.  Am J Physiol  1981; 241(1):F85-F93.

56. Brenner BM, Meyer TW, Hostetter TH: Dietary protein intake and the progressive nature of kidney disease: The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease.  N Engl J Med  1982; 307(11):652-659.

57. Berg BN, Simm HS: Nutrition and longevity in the rat. II. Longevity and onset of disease with different levels of food intake.  J Nutr  1960; 71:255.

58. Couser WG, Stilmant MM: Mesangial lesions and focal glomerular sclerosis in the aging rat.  Lab Invest  1975; 33(5):491-501.

59. Robertson JL, Goldschmidt M, Kronfeld DS, et al: Long-term renal responses to high dietary protein in dogs with 75% nephrectomy.  Kidney Int  1986; 29(2):511-519.

60. Bourgoignie JJ, Gavellas G, Hwang KH, et al: Renal function of baboons (Papio hamadryas) with a remnant kidney, and impact of different protein diets.  Kidney Int Suppl  1989; 27:S86-S90.

61. Davies DF, Shock NW: Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males.  J Clin Invest  1950; 29:496.

62. Kaplan C, Pasternack B, Shah H, Gallo G: Age-related incidence of sclerotic glomeruli in human kidneys.  Am J Pathol  1975; 80(2):227-234.

63. Fetterman GH, Habib R: Congenital bilateral oligonephronic renal hypoplasia with hypertrophy of nephrons (oligoméganéphronie): Studies by microdissection.  Am J Clin Pathol  1969; 52:199.

64. Bernstein J: Renal hypoplasia and dysplasia.   In: Edelmann Jr CM, ed. Pediatric Kidney Disease,  Boston: Little, Brown; 1978:541.

65. Kiprov DD, Colvin RB, McCluskey RT: Focal and segmental glomerulosclerosis and proteinuria associated with unilateral renal agenesis.  Lab Invest  1982; 46(3):275-281.

66. Emanuel B, Nachman R, Aronson N, Weiss H: Congenital solitary kidney. A review of 74 cases.  Am J Dis Child  1974; 127(1):17-19.

67. Andersen B, Hansen JB, Jorgensen SJ: Survival after nephrectomy.  Scand J Urol Nephrol  1968; 2(2):91-94.

68. Zucchelli P, Cagnoli L, Casanova S, et al: Focal glomerulosclerosis in patients with unilateral nephrectomy.  Kidney Int  1983; 24(5):649-655.

69. Baudoin P, Provoost A, Molenaar J: Renal function up to 50 years after unilateral nephrectomy in childhood.  Am J Kidney Dis  1993; 21(6):603-611.

70. Narkun-Burgess DM, Nolan CR, Norman JE, et al: Forty-five year follow-up after uninephrectomy.  Kidney Int  1993; 43:1110-1115.

71. Lhotta K, Eberle H, Konig P, Dittrich P: Renal function after tumor enucleation in a solitary kidney.  Am J Kidney Dis  1991; 17(3):266-270.

72. Foster MH, Sant GR, Donohoe JF, Harrington JT: Prolonged survival with a remnant kidney.  Am J Kidney Dis  1991; 17(3):261-265.

73. Novick AC, Gephardt G, Guz B, et al: Long-term follow-up after partial removal of a solitary kidney.  N Engl J Med  1991; 325(15):1058-1062.

74. Tapson JS: End-stage renal failure after donor nephrectomy.  Nephron  1986; 42(3):262-264.

75. Ladefoged J: Renal failure 22 years after kidney donation.  Lancet  1992; 339(8785):124-125.

76. Najarian JS, Chavers BM, McHugh LE, Matas AJ: 20 years or more of follow-up of living kidney donors.  Lancet  1992; 340:807-810.

77. Ramcharan T, Matas A: Long term (20-37 years) follow-up of living kidney donors.  Am J Transplant  2002; 2(10):952-964.

78. Ibrahim H, Rogers T, Humar A, Matas A: Prevalence of chronic kidney disease years after donor nephrectomy.  Am J Transplant  2005; 5:531.

79. Fattor R, Silva F, Eigenbrodt E, et al: Effect of unilateral nephrectomy on three patients with histopathological evidence of diabetic glomerulosclerosis in the resected kidney.  J Diabet Complications  1987; 1(3):107-113.

80. Sampson MJ, Drury PL: Development of nephropathy in diabetic patients with a single kidney.  Diabetic Med  1990; 7:258-260.

81. Silveiro S, da Costa L, Beck M, Gross J: Urinary albumin excretion rate and glomerular filtration rate in single kidney type 2 diabetic patients.  Diabetes Care  1998; 21:1521-1524.

82. Stern MP, Williams K, Haffner SM: Identification of persons at high risk for type 2 diabetes mellitus: Do we need the oral glucose tolerance test?.  Ann Intern Med  2002; 136(8):575-581.

83. Manjunath G, Tighiouart H, Ibrahim H, et al: Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community.  J Am Coll Cardiol  2003; 41:47-55.

84. Go A, Cherton G, Fan D, et al: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.  N Engl J Med  2004; 351:1296-1305.

85. Foley R, Murray A, Li S, Herzog C, et al: Chronic kidney disease and the risk for cardiovascular disease, renal replacement and death in the United States Medicare population 1998-1999.  J Am Soc Nephrol  2005; 46:489-495.

86. Chagnac A, Weinstein T, Korzets A, et al: Glomerular hemodynamics in severe obesity.  Am J Physiol Renal Physiol  2000; 278(5):F817-F822.

87. Kembham J, Markowitz G, Valeri A, et al: Obesity-related glomerulopathy: An emerging epidemic.  Kidney Int  2001; 59:1498-1509.

88. Sibley S, Zhan L, Ibrahim H: Urinary TGFb-1 is related to body fat distribution.  J Am Soc Nephrol  2004; 15:708A.

89. Heimback J, Taler S, Prieto M, et al: Obesity in living kidney donors: Clinical characteristics and outcomes in the era of laparoscopic donor nephrectomy.  Am J Transplant  2005; 5(5):1057-1064.

90. Hsu C, McCulloch C, Iribarren C, et al: Body mass index and risk of end stage renal disease.  Ann Intern Med  2006; 144(1):21-28.

91. Flaherty K, Fuchs C, Colditz G, et al: A prospective study of body mass index, hypertension, and smoking and the risk of renal cell carcinoma.  Cancer Causes Control  2005; 16:1099-1106.

92. Textor S, Taler S, Driscoll N, et al: Blood pressure and renal function after kidney donation from hypertensive live donors.  Transplantation  2004; 78(2):276-282.

93. Kasiske B, Ravenscraft M, Ramos E, et al: he evaluation of living renal transplant donors: Clinical practice guidelines  1996; 7(11):2288-2313.

94. Koushik R, Garvey C, Manivel C, et al: Persistent, asymptomatic, microscopic hematuria in prospective kidney donors.  Transplantation  2005; 80:1425-1429.

95. Hunt J, van der Hel O, McMillan G, et al: Renal cell carcinoma in relation to cigarette smoking: Meta-analysis of 24 studies.  Int J Cancer  2005; 114:101-108.

96. Ejerblad E, Fored C, Lindblad P, et al: Association between smoking and chronic renal failure in a nationwide population-based case-control study.  J Am Soc Nephrol  2004; 15:2178-2185.

97. Haroun M, Jaar B, Hoffman S, et al: Risk factors for chronic kidney disease: A prospective study of 23,534 men and women in Washington County, Maryland.  J Am Soc Nephrol  2003; 14:2934-2941.

98. Orth S: Effects of smoking on systemic and intrarenal hemodynamics: Influence on renal function.  J Am Soc Nephrol  2004; 15:S58-S63.