Kidney transplantation in adults: Evaluation of the living kidney donor candidate

INTRODUCTION — The number of patients awaiting kidney transplantation has steadily increased over time. The gap between allograft supply and demand continues to widen despite initiatives to expand the use of nonstandard deceased-donor allografts.

The use of organs from living donors is one strategy to address the need for transplants. After a steady decline in living donation in the United States from 2005 to 2014, followed by a plateau, the number of living kidney donations increased progressively from 2017 to 2019, reaching the highest annual count to date of 6867 [1]. While reflecting important progress, only a small proportion of the waiting list receives living-donor transplants each year [1]. The declaration of the coronavirus disease 2019 (COVID-19) pandemic in March 2020 substantially impacted the practice of living-donor kidney transplantation, which was considered "elective" surgery at many centers and was generally halted to avoid risk of infection in living donors and recipients [2,3]. In contrast with the prompt recovery of deceased donor kidney transplantation rates, living-donor kidney transplantation in 2020 and 2021 lagged behind 2019 levels, with particular disparities for Black patients.

Recipients of allografts from living donors receive significant graft and patient survival advantages over those who receive deceased-donor grafts. In addition, living-donor transplants may be performed with minimal delay and controlled scheduling, which permits preemptive transplantation (transplantation prior to dialysis) or transplantation early in a recipient's course of kidney failure. (See "Kidney transplantation in adults: Risk factors for graft failure" and "Kidney transplantation in adults: Timing of transplantation and issues related to dialysis".)

While most donors experience good outcomes and have good quality of life after donation, kidney donation is associated with short- and longer-term risks [4,5]. Risks of donation include surgical, medical, psychosocial, and financial complications. (See "Kidney transplantation in adults: Risk of living kidney donation".)

In February 2013, the Organ Procurement and Transplantation Network (OPTN) implemented policy requirements for all living kidney donor recovery hospitals in the United States in order to promote consistency in the informed consent, medical and psychosocial evaluation, and follow-up of living donors [6]. In 2014, these requirements were incorporated within global polices for living organ donors and modified in 2017 to include new risk information in required elements of informed consent. Mandated exclusion criteria for United States living donors were updated in 2022. These policies define the minimum requirements for the evaluation and selection of living kidney donors in the United States and are available online.

OPTN requirements may be expanded upon in center-specific protocols to address topics not covered in OPTN mandates, including additional testing required on a case-by-case basis. Our approach is largely consistent with the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) "Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors," which provides a framework for donor candidate evaluation grounded in simultaneous consideration of the combined impact of each candidate's profile of demographic (ie, age, sex, and race) and health characteristics (eg, kidney function, blood pressure, body mass index, smoking status) on their risk of serious adverse outcomes after donation, most notably kidney failure (figure 1) [5]. To support this framework, an online risk tool was developed to estimate projected risk of end-stage kidney disease (ESKD; in the absence of donation) for donor candidates based on a profile of 10 demographic and health factors [7].

All donor candidates should be evaluated using the same criteria, regardless of whether donation is directed towards a designated recipient [5].

The evaluation of a living kidney donor candidate, including the OPTN requirements, is discussed here. The risks associated with living kidney donation are discussed elsewhere (see "Kidney transplantation in adults: Risk of living kidney donation"). The evaluation of the kidney transplant recipient is discussed separately. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient".)

DONOR EVALUATION — The Organ Procurement and Transplantation Network (OPTN) requirements specify that the following be performed and documented prior to living kidney donation [6]:

●Blood typing (performed on two separate occasions before the recovery).

●A medical evaluation (performed by a clinician or surgeon with experience in living donation).

●A psychosocial evaluation (performed by a psychiatrist, psychologist, masters-prepared social worker, or licensed clinical social worker).

●Living-donor recovery hospitals must designate and provide each living-donor candidate with an Independent Living Donor Advocate (ILDA; one person or a team with a key contact) who is not involved with the potential recipient evaluation and is independent of the decision to transplant the potential recipient to ensure that the donor has received information on all phases of the donation process and to advocate for the rights of the donor. The OPTN ILDA requirements also fulfill the requirements of Centers for Medicare and Medicaid Services (CMS).

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) living donor guideline offers a checklist to guide the evaluation, care, and follow-up of living kidney donors (table 1) [5,8] and a summary of roles and responsibilities of members of the evaluation team (table 2).

Blood typing and crossmatch — The evaluation of a living kidney donor candidate begins with an assessment of the donor and recipient blood groups and a crossmatch compatibility [6,9]. The blood type and crossmatch compatibility are the primary criteria for biological compatibility of the donor and recipient. OPTN policy requires prospective crossmatch testing of transplant candidates prior to placement of living-donor organs [6]. (See "Kidney transplantation in adults: Overview of HLA sensitization and crossmatch testing".)

As per OPTN requirements, the recovery hospital must ensure that ABO typing is performed on two separate occasions prior to donation and use source documents to register the living donor [6]. If the initial subtype test indicates the donor to be blood type A, non-A1 or blood type AB, non-A1B, the recovery hospital must ensure that a second subtype determination test is performed prior to donation. The crossmatch between potential donor and recipient is done to detect preformed anti-donor antibodies in recipient blood that would cause early failure of the allograft [10].

Donor candidates who are ABO blood group or crossmatch incompatible with their intended recipient should be informed of the availability, risks, and benefits of treatment options, including kidney paired donation and incompatibility management strategies [5,11]. Issues surrounding ABO incompatibility and human leukocyte antigen (HLA) sensitization are discussed separately, with some programs offering transplantation across such barriers.

●(See "Kidney transplantation in adults: ABO-incompatible transplantation".)

●(See "Kidney transplantation in adults: HLA-incompatible transplantation".)

●(See "Kidney transplantation in adults: Kidney paired donation".)

Most kidney transplant programs routinely perform HLA typing to support counseling about projected graft survival and to optimize HLA matching in the event that there is more than one donor candidate [5]. However, HLA matching between a particular donor and recipient is not required for successful transplantation. In some centers, HLA typing is not performed for most donors, because outcomes are acceptable even without HLA matching in the current era of improved immunosuppressive regimens [10,12]. As an example, allograft survival with an unrelated, living donor is similar to that from a one-haplotype-matched, living donor [13]. Aside from HLA-identical twins, there are minimal differences in the survival of allografts from biologically related compared with unrelated donors under modern immunosuppression. (See "Kidney transplantation in adults: Living unrelated donors".)

As Rh antigens are not expressed on kidney tissue cell surfaces, this antigen system does not play a major role in allograft rejection, and matching for Rh antigens is not relevant in most settings. However some, though not all [14], evidence suggests that Rh antigen mismatching may be associated with a small reduction in allograft survival [15]. In addition, female Rh-negative recipients of childbearing age may be at risk for sensitization when the donor is Rh positive [16,17].

Medical evaluation — Once a living-donor candidate is screened for blood type and crossmatch compatibility with the intended recipient, a thorough medical, surgical, and psychosocial evaluation is performed [6]. The overall purpose is to ensure that the donor candidate is in good health, has normal kidney function and structure, is not a risk to the recipient with respect to disease transmission, and will not face known unacceptable risks after donation.

History and physical examination — The OPTN requires assessment and documentation of the following evaluation components prior to donation:

●A personal history of significant medical conditions, including but not limited to hypertension, past evaluation for coronary artery disease, lung disease, heart disease, gastrointestinal disease, autoimmune disease, neurologic disease, genitourinary disease, hematologic disorders, bleeding or clotting disorders, history of cancer including melanoma, history of infections, and allergies. We agree with the KDIGO guideline that donor candidates should also be asked about risk factors for kidney and cardiovascular disease and prior episodes of gout [5]. Women should be asked about prior hypertensive disorders of pregnancy (eg, gestational hypertension, preeclampsia, or eclampsia) and future childbearing plans [5].

●A kidney-specific personal history including genetic kidney diseases; kidney disease, proteinuria, and hematuria; kidney injury; diabetes, including gestational diabetes; nephrolithiasis; and recurrent urinary tract infections.

●Active and past medications, including nephrotoxic medications and chronic use of pain medication.

●Family history including history of coronary artery disease, cancer (including kidney cancer), kidney disease, diabetes, and hypertension. When a family history of kidney disease is present, the type of disease, time of onset, and extrarenal manifestations associated with the disease should be determined if possible (including requests for permission to review recipient health information when relevant) [5].

●Social history including occupation, employment, and health insurance status; living arrangements; social support; smoking, alcohol, and drug use and abuse; psychiatric illness, depression, and suicide attempts; and an assessment of risk criteria for acute human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection, as defined by the United States Public Health Service (USPHS). A requirement for the assessment and documentation for social history within the medical evaluation is in addition to the requirement for review of these elements within the psychosocial evaluation. In addition to OPTN policy requirements, we agree with KDIGO that the social history include factors associated with increased likelihood of transmissible infections, including risks related to travel and geographic exposures, hobbies, animal-related exposures, and other exposures [5]. (See 'Laboratory and imaging tests' below.)

To screen for behaviors that confer increased risk for HIV, HBV, or HCV infection in the potential donor, the OPTN requires assessment and documentation of behaviors defined by the USPHS as associated with increased risk of transmission of HIV, HBV, or HCV infections prior to donation (table 3) [18].

Physical exam should include vital signs, examination of all major organ systems, measurement of height and weight, and computation of body mass index (BMI). Blood pressure must be measured on at least two occasions or by 24-hour or overnight ambulatory blood pressure monitoring (ABPM).

Laboratory and imaging tests — The OPTN requires performance of the following laboratory and imaging tests as part of the donor evaluation [6]:

●Complete blood count with platelet count; blood type and subtype determination as noted above; prothrombin time (PT) or international normalized ratio (INR); partial thromboplastin time (PTT); metabolic testing (including blood urea nitrogen [BUN]); serum creatinine; fasting blood glucose; electrolytes; calcium and phosphorus; albumin, transaminase levels, and alkaline phosphatase; fasting lipid profile (total, high-density lipoprotein [HDL], and low-density lipoprotein [LDL] cholesterol; triglycerides).

●Glucose tolerance test or glycosylated hemoglobin (HbA1C) in those with a family history of diabetes in a first-degree relative or who are deemed at high metabolic risk for other reasons (eg, personal history of gestational diabetes). At some centers, including ours, HbA1C is tested in all donor candidates, regardless of metabolic risk [19].

●Urinalysis with microscopy; urine culture (if clinically indicated).

●Measurement of urinary protein and albumin excretion.

●Measurement of glomerular filtration rate (GFR) by isotopic methods or a creatinine clearance calculated from a 24-hour urine collection.

●Living-donor recovery hospitals must develop and comply with a written protocol for screening for polycystic kidney disease (PKD) and other inherited kidney diseases as guided by family history. We evaluate living-donor candidates with a family history of autosomal dominant polycystic kidney disease (ADPKD) by genotyping (including genotyping of the index case, when available) if age <40 years and there is one or more cysts present (by computed tomography [CT] scan or ultrasound) or if age ≥40 years and there is more than one cyst on imaging [20]. Targeted gene panels for known mutations implicated in kidney diseases that may be useful for the evaluation of living-related-donor candidates are being developed and validated [21,22].

●Donor candidates with a history of kidney stones or nephrolithiasis (>3 mm) identified on imaging must have a 24-hour urine stone panel including calcium, oxalate, uric acid, citric acid, creatinine, and sodium.

●A human chorionic gonadotropin (HCG) quantitative pregnancy test in premenopausal women who have not had surgical sterilization.

●Electrocardiogram.

●Chest radiograph.

●Anatomic assessment of kidneys by imaging to assess equality of kidney size and evaluate for masses, cysts, stones, or other structural defects to help determine the kidney best suited for donation. The type of test is determined by hospital and may include either CT angiogram or magnetic resonance (MR) angiogram [23].

The OPTN requires screening for transmissible infectious diseases with tests performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory or in a laboratory meeting equivalent requirements as determined by CMS, using US Food and Drug Administration (FDA)-licensed, approved, or cleared tests. Testing must include all of the following:

●Cytomegalovirus (CMV) antibody.

●Epstein-Barr virus (EBV) antibody.

●HIV antibody (anti-HIV) testing or HIV antigen/antibody (Ag/Ab) combination test as close as possible but within 28 days prior to organ recovery.

●Hepatitis B surface antigen (HBsAg) testing as close as possible but within 28 days prior to organ recovery.

●Hepatitis B core antibody (anti-HBc) testing as close as possible but within 28 days prior to organ recovery.

●HBV nucleic acid testing (NAT) as close as possible but within 28 days prior to organ recovery.

●Hepatitis C antibody (anti-HCV) testing as close as possible but within 28 days prior to organ recovery.

●HCV NAT as close as possible but within 28 days prior to organ recovery.

●Syphilis testing.

●Living-donor recovery hospitals must determine if the donor is at increased risk for infection with Mycobacterium tuberculosis (MTB), and, if MTB risk is suspected, testing must include screening for latent infection using either purified protein derivative (PPD) or interferon-gamma release assay (IGRA) [24].

●Each living-donor recovery hospital must develop and follow a written protocol for identifying and testing donors at risk for transmissible seasonal or geographically defined endemic diseases [25,26]. Such infections may include Strongyloides, Trypanosoma cruzi, and West Nile virus if the donor candidate is from or has traveled to endemic areas. In addition, testing for Chagas and toxoplasma antibodies is recommended for children of women who lived in endemic regions of Mexico or Central or South America and persons who have received a blood transfusion in endemic regions [27].

We agree with guidance from the OPTN/United Network for Organ Sharing (UNOS) Ad Hoc Disease Transmission Advisory Committee (DTAC), the American Society of Transplantation (AST), and the American Society of Transplant Surgeons (ASTS) that donor deferral should be considered if there is history of travel to Zika-endemic areas in the 28 days prior to donation. In the case of potential living donors with Zika infection, donation should be deferred where possible [28]. We also agree with KDIGO that transplant programs develop protocols to screen donor candidates for emerging infections (eg, Ebola, Zika, severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], mpox [monkeypox]) in consultation with local public health specialists [5,29,30]. (See "COVID-19: Issues related to solid organ transplantation", section on 'Donor screening'.)

We recommend that recovery hospitals counsel approved donor candidates to avoid travel to areas with Centers for Disease Control and Prevention (CDC) warning for endemic disease risks between approval and donation and repeat the travel history if the time between approval and scheduled donation is prolonged.

OPTN requirements for predonation cancer screening include the following:

●Recovery hospitals must develop and comply with protocols consistent with the American Cancer Society (ACS) or the US Preventive Services Task Force (USPSTF) to screen for:

•Cervical cancer

•Breast cancer

•Prostate cancer

•Colon cancer

•Lung cancer

●While the ACS and USPSTF do not identify an evidence base to support routine skin cancer screening, we perform a complete skin examination for people with increased recreational or occupational exposure to sunlight, family or personal history of skin cancer, or clinical evidence of precursor lesions.

We also review pathology reports for donors with a history of skin lesion removal.

Beyond the minimum requirements defined by the OPTN, further forms of testing within center-specific protocols may be guided by local experience or as needed on a case-by-case basis and may include echocardiography, cardiac stress testing, cystoscopy, kidney biopsy, and other tests such as apolipoprotein (L1) genotyping in donor candidates with sub-Saharan African ancestors [5,31,32]. Genetic testing in the living-donor candidate evaluation has become more feasible with increased availability of genetic kidney panels. Testing should occur in concert with genetic counseling and, in the case of donation to a related recipient, should start with testing of the recipient candidate in most circumstances to identify a specific disease-causing variant to ground reassurance if that variant is not identified in the living-donor candidate [22]. Ancestry-based testing related to apolipoprotein L1 (APOL1) is an exception. Pending results from these ongoing studies such as the NIH-funded APOL1 Long-term Outcomes Study (APOLLO), the 2017 KDIGO guideline recommends informing Black donor candidates that having two APOL1 kidney risk variants may increase the lifetime risk of kidney failure, but that the precise postdonation kidney failure risk cannot presently be quantified for individuals with high-risk APOL1 genotypes.

Psychosocial evaluation — OPTN mandates performance of a psychosocial evaluation by a psychiatrist, psychologist, masters-prepared social worker, or licensed clinical social worker prior to donation, including documentation of the following [6]:

●Evaluation for any psychosocial issues, including mental health issues, that might complicate the living donor's recovery and could be identified as risks for poor psychosocial outcome.

●Evaluation for the presence of behaviors that may increase risk for HIV, HBV, or HCV transmission as defined by the USPHS guideline [18].

If increased-risk behaviors are identified, the donor candidate is advised about the disclosure of such behaviors to the recipient and offered the option of withdrawing from donation prior to (ie, without) disclosure.

●Review of the living donor's history of smoking, alcohol, and drug use, abuse, and dependency.

●Identification of factors that warrant educational or therapeutic intervention prior to the final donation decision.

●Determination that the living donor understands the short- and long-term medical and psychosocial risks for both the living donor and recipient associated with living donation.

●Assessment of whether the decision to donate is free of inducement, coercion, and other undue pressure by exploring the reasons for donating and the nature of the relationship, if any, to the transplant candidate.

●Assessment of the living donor's ability to make an informed decision and the ability to cope with the major surgery and related stress. This includes evaluating whether the donor has a realistic plan for donation and recovery, with social, emotional, and financial support available as recommended.

●Review of the living donor's occupation, employment status, health insurance status, living arrangements, and social support.

●To ensure voluntariness, at least a portion of the psychosocial evaluation of the donor candidate should be performed in the absence of the intended recipient, family members, and other persons who could influence the donation decision [5].

Required elements of the OPTN psychosocial evaluation policy that are also included in the medical evaluation must be performed and documented within each evaluation.

Independent Living Donor Advocate — Per OPTN requirements, living-donor recovery hospitals must designate and provide each donor candidate with an ILDA (one person or a team with a key contact) who is not involved with the potential recipient evaluation and is independent of the decision to transplant the potential recipient. The ILDA must have adequate qualification and training requirements regarding knowledge of living organ donation, transplantation, medical ethics, informed consent, and the potential impact of family or other external pressure on the living donor's decision about whether to donate. To fulfill OPTN and CMS requirements, qualifications of the ILDA should be specified in each recovery hospital's protocols, and fulfillment of each requirement must be documented.

As per the OPTN requirement, the ILDA must [6]:

●Function independently from the transplant candidate's team

●Advocate for the rights of the living donor

●Review whether the living donor has received information on each of the following areas: informed consent, the evaluation process, the surgical procedure, medical and psychosocial risks, and follow-up requirements

●Assist the donor in obtaining additional information from other professionals as needed

To help clarify and optimize the ILDA role, the AST's Live Donor Community of Practice (LDCOP) offered consensus-based recommendations, including that [33]:

●The ILDA must have a certain skillset rather than a specific profession.

●The ILDA's primary role is to assess components of informed consent.

●Independence of the ILDA must be transparently defined and be supported by reporting structure.

●The ILDA role should be integrated across the donor-care continuum.

As formalization of the ILDA role is relatively recent in the practice of living donation, knowledge gaps remain in defining evidence-based best practices of living-donor advocacy, warranting targeted research efforts.

CONTRAINDICATIONS TO LIVING KIDNEY DONATION

Absolute contraindications defined by OPTN — The following are the minimum absolute exclusions defined by the Organ Procurement and Transplant Network (OPTN) [6]:

●Both age <18 years and mentally incapable of making an informed decision.

●Uncontrolled hypertension or history of hypertension with end-organ damage.

●HIV infection, unless the requirements for a variance are met, including institutional review board (IRB) approval consistent with research criteria published by the National Institutes of Health and OPTN approval [34].

●Type 1 diabetes.

●Type 2 diabetes where an individualized assessment of donor demographics or comorbidities reveals either evidence of end organ damage or unacceptable lifetime risk of complications.

●Active or incompletely treated malignancy that either requires treatment other than surveillance or has more than minimal known risk of transmission. However, policy revision in 2016 permits transplantation of organs removed as part of treatment for an individual's health condition (termed "therapeutic donation" by the OPTN) under center-specific written protocols. (See 'Malignancy' below.)

●Evidence of acute symptomatic infection (until resolved).

●High suspicion of donor coercion.

●High suspicion of illegal financial exchange between donor and recipient.

●Uncontrolled, diagnosable psychiatric conditions requiring treatment before donation, including evidence of suicidality.

●Any condition that in the hospital's medical judgment causes the donor to be unsuitable for organ donation.

Possible contraindications beyond OPTN requirements — Although there is substantial variability in the criteria used to exclude potential donors, some contraindications raised in clinical practice guidelines and used in our practice include [5,12,35-42]:

●ABO or human leukocyte antigen (HLA) incompatibility without a planned management protocol and informed consent (see "Kidney transplantation in adults: HLA-incompatible transplantation"). Biologically incompatible donor-recipient pairs should also be educated about opportunities for participation in donor-exchange programs.

●Proteinuria and/or hematuria. (See 'Albuminuria' below and 'Hematuria' below.)

●Impaired kidney function. (See 'Kidney function' below.)

●When asymmetry in glomerular filtration rate (GFR), parenchymal abnormalities, vascular abnormalities, or urological abnormalities are present but do not preclude donation, the more severely affected kidney should be used for donation [5]. Procurement of a living-donor kidney with three or more arteries should only be undertaken by surgeons with adequate experience [5].

●Any chronic, active viral infection (human T-lymphotropic virus [HTLV], hepatitis B virus [HBV], and hepatitis C virus [HCV]).

●History of malignancy, especially lung, breast, renal or urologic, gastrointestinal, or hematologic cancers and melanoma. Donor candidates with a history of treated cancer that has a low risk of transmission or recurrence may be acceptable for donation on a case-by-case basis [5].

●Current pregnancy.

●Chronic illness, particularly pulmonary, liver, autoimmune, neurologic, or cardiac disease.

●Hypertension in higher-risk candidates or hypertension with end-organ damage. (See 'Hypertension' below.)

●Nephrocalcinosis, bilateral kidney stones, or recurrent nephrolithiasis. (See 'History of nephrolithiasis' below.)

●Two apolipoprotein L1 (APOL1) risk alleles [31,43].

●Disorders requiring anticoagulation.

●History of sickle cell trait [44].

●Class II or III obesity [12,36].

●Family history of renal cell cancer.

●Active substance or alcohol abuse disorder.

●Marked ambivalence to donation [45].

Increased risk of diabetes — As per the OPTN guidelines, donor candidates with a family history of diabetes should be evaluated with a glucose tolerance test or glycosylated hemoglobin [6]. Patients that are considered to be a high metabolic risk for diabetes should also be evaluated; such patients include those with an elevated fasting glucose or a history of gestational diabetes.

Diabetes mellitus was considered an absolute exclusion to donation in OPTN policy until 2022 and in most clinical practice guidelines internationally [12,36,38,41,46]. The European Best Practices qualifies an exception of "exceptional circumstances" [41], and the British Transplantation Society offers the opinion-based recommendation that "diabetics can be considered for kidney donation after a thorough assessment of the lifetime risk of cardiovascular and progressive kidney disease in the presence of a single kidney" [42]. A study of 8280 donors, including 1826 with impaired fasting glucose at the time of donation and 6204 without, found similar survival and rates of end-stage kidney disease (ESKD) among those with or without impaired fasting glucose over a mean follow-up of 15.7 years [47]. Based on such emerging data, in 2022, OPTN policy was revised to maintain the exclusion for type 1 diabetes but to restrict the absolute exclusion for type 2 diabetes to cases where an individualized assessment of donor demographics or comorbidities reveals either evidence of end organ damage or unacceptable lifetime risk of complications.

Exclusion criteria based upon prediabetic status or diabetes risk factors vary across recovery hospitals due to lack of strong evidence. A survey of United States centers in 2005, for example, found that patients with fasting glucose values >100, 110, and 120 mg/dL are excluded in 37, 7, and 5 percent of centers, respectively [40]; in addition, 61 and 64 percent of centers exclude those with a two-hour value in an oral glucose tolerance test >140 mg/dL or with type 2 diabetes mellitus, respectively.

We agree with Kidney Disease: Improving Global Outcomes (KDIGO) that the decision to approve donor candidates with prediabetes should be individualized based on demographic and health profile in relation to the transplant program's acceptable risk threshold, including projected risk of kidney failure estimated from consideration of all baseline factors [5].

Based on systematic evidence review and the guideline framework, KDIGO includes a similar recommendation for individualization to allow consideration of very-low-risk (generally older) persons with type 2 diabetes [5]. However, this recommendation is not applicable to United States practice, given the OPTN exclusion for diabetes.

Age — There is no absolute upper age limit for kidney donation. Previously, donor candidates >50 years of age were often not considered suitable. However, donor candidates age 50 years and older are now commonly accepted if these individuals are in good physical and mental condition and have adequate kidney function. For example, increased use of older donors was reflected in a 2005 survey of kidney transplant centers in the United States in which almost 60 percent of centers had no upper age limit for kidney donors [40]. Among the remaining centers, an age limit of 75, 70, 65, 60, and 55 years was reported in 4, 5, 21, 7, and 1 percent, respectively. However, the survival of kidney allografts from donors older than 70 years is lower than those from younger donors. In addition, donors older than 60 years are more likely to have persistently reduced estimated GFR (eGFR) after nephrectomy to <60 mL/min. These data are discussed elsewhere. (See "Kidney transplantation in adults: Risk of living kidney donation", section on 'Long-term risks'.)

As noted above, the OPTN defines age <18 years and an inability to make decisions as exclusion criteria. (See 'Absolute contraindications defined by OPTN' above.)

Kidney function — OPTN policy requires measurement of kidney function, either by measured GFR or a 24-hour creatinine clearance [6]. From the perspective of international practice, KDIGO recommends use of eGFR from serum creatinine for initial assessment, followed by confirmation with one or more additional measurements, depending on availability: measured GFR, 24-hour creatinine clearance, eGFR from the combination of serum creatinine and cystatin C (eGFRcr-cys), or repeat eGFR [5,48]. The last option (ie, repeat eGFR) is the least preferred.

To support the guideline, a web-based calculator was developed to compute posttest probabilities for measured GFR above or below threshold probabilities for decision making [49]. The tool has been validated in one study of donor candidates [50], suggesting that eGFR may be sufficiently accurate for decision making without the need for measured GFR in many cases. However, the use of eGFR alone is not recognized by OPTN policy, but a strategy of screening with eGFR followed by confirmation with 24-hour creatinine clearance or measured GFR can be efficient and policy compliant. (See "Assessment of kidney function".)

If kidney function is evaluated via a creatinine clearance, the adequacy of the 24-hour urine collection should be carefully assessed (see "Calculation of the creatinine clearance"). Furthermore, the dietary intake of protein should be at least 1 g of protein per kg of body weight since a low-protein diet may decrease creatinine clearance by as much as 10 mL/min [51].

Past guidelines cited a GFR level of 80 mL/min as the minimal threshold for an acceptable level of kidney function for donation [12]. However, based on lack of evidence for a single GFR threshold from systematic review, we believe a higher threshold value of GFR (≥90 mL/min/1.73 m²) should be used for the routine acceptance of a donor candidate, and a lower threshold value of GFR (<60 mL/min/1.73 m²) should be used to routinely decline a donor candidate. In the intermediate range of GFR (60 to 89 mL/min/1.73 m²) [5], the decision to approve should be individualized based on demographic and health profile in relation to the transplant program's acceptable risk threshold, including projected risk of kidney failure estimated from simultaneous consideration of all baseline factors [5].

Albuminuria — OPTN requires measurement of urine protein and albumin excretion but does not specify measure modalities or exclusion thresholds.

Urine albumin is the preferred measure of urine protein for assessment of kidney damage [52].

The initial evaluation of donor albuminuria (screening) should be performed using urine albumin-to-creatinine ratio (ACR) in a random (untimed) urine specimen [5], followed by confirmation with albumin excretion rate (AER; mg/day) in a timed urine specimen, or repeat ACR if AER cannot be obtained [5].

Acceptable donor candidates should have an AER less than 30 mg/day [5]. Donor candidates with AER greater than 100 mg/day should not be accepted [5].

Approval of donor candidates with AER 30 to 100 mg/day should be individualized based on demographic and health profile in relation to the transplant program's acceptable risk threshold, including projected risk of kidney failure estimated from simultaneous consideration of all baseline factors [5].

A 2007 survey of practices by transplant programs in the United States reported that 36 percent used protein excretion rates >150 mg/day as a threshold for donor exclusion (unless proteinuria is postural), while 44 percent reported higher exclusion thresholds of 300 mg/day or higher [40].

Hematuria — Donor candidates should be assessed for microscopic hematuria [5]. The definition of hematuria appears to vary across transplant centers. We define hematuria as more than 2 to 5 red blood cells (RBCs) per high-powered field (hpf). In the United States, some centers define hematuria as at least 10 RBC/hpf, while others use 3 RBC/hpf [40]. In one study, living kidney donors who had hematuria defined as the presence of >3 RBC/hpf developed a progressive decline in kidney function [53].

Donor candidates with persistent microscopic hematuria on two to three occasions and unrelated to exercise, trauma, sexual activity, or menstruation) should undergo testing to identify possible causes, which may include (algorithm 1) [5]:

●Urinalysis and urine culture to assess for infection

●Cystoscopy and imaging to assess for urinary tract malignancy

●Twenty-four-hour urine stone panel to assess for nephrolithiasis and/or microlithiasis

●Kidney biopsy to assess for glomerular disease (eg, thin basement membrane nephropathy, immunoglobulin A [IgA] nephropathy, Alport syndrome)

The degree to which hematuria excludes donor candidates varies across transplant programs. Some programs exclude donor candidates with >10 RBC/hpf. Others will accept a donor candidate with hematuria if the urologic evaluation and kidney biopsy are negative.

Hypertension — We agree with the 2017 KDIGO guidelines that normal blood pressure should be defined by guidelines for the general population in the country or region where donation is planned [5].

Detection of hypertension is principally performed by measuring blood pressure in the clinic. When the presence or absence of hypertension in a donor candidate is indeterminate based on history and clinic measurements (eg, blood pressure is high normal or variable), the blood pressure should be further evaluated using ABPM or repeated using standardized blood pressure measurements [5].

Uncontrollable hypertension, or a history of hypertension with evidence of end-organ damage, is an absolute contraindication to living kidney donation per OPTN policy [6]. (See 'Absolute contraindications defined by OPTN' above.)

There is variability across transplant programs in the acceptance of donor candidates with well-controlled hypertension. In a 2005 survey of kidney transplant centers in the United States, 47 and 41 percent of centers excluded patients taking any antihypertensive medication or taking more than one medication, respectively [40].

A 2011 American Society of Transplantation (AST)/American Society of Transplant Surgeons (ASTS)/North American Transplant Coordinators Organization (NATCO)/United Network for Organ Sharing (UNOS) Joint Societies Work Group on Evaluation of the Living Kidney Donor recommended that donation from healthy, older (age ≥50 years) White people with hypertension may be acceptable [36], based on demonstration of short-term safety in this group [54].

The risk to donors who have a family history of hypertension is less clear. Few data have been published that specifically examine the outcome of such patients [10,55].

Donor candidates with hypertension that can be controlled to normal blood pressure using one or two antihypertensive agents, who do not have evidence of target organ damage, may be acceptable for donation [5].

The decision to approve donor candidates with hypertension should be individualized based on demographic and health profile in relation to the transplant program's acceptable risk threshold.

History of nephrolithiasis — Donor candidates should be asked about prior kidney stones, review of related medical records in those with a history of stones (if available), and review of imaging performed to assess anatomy before donor nephrectomy (eg, computed tomographic [CT] angiogram) for the presence of kidney stones [5]. Donor candidates with prior or current kidney stones should be assessed for an underlying cause [5]. The OPTN requires that donor candidates with a history of nephrolithiasis or nephrolithiasis observed by imaging have a 24-hour urine stone panel [6]. (See "Kidney stones in adults: Evaluation of the patient with established stone disease", section on '24-hour urine collections'.)

Based on a 2005 survey, the majority of United States transplant centers will accept a donor candidate with a history of nephrolithiasis if the evaluation reveals the absence of stones and metabolic studies are normal [40]. Patients with overt metabolic abnormalities that are associated with increased stone risk are generally excluded from kidney donation (see "Kidney stones in adults: Epidemiology and risk factors"). Such abnormalities include very low citrate and very high calcium or oxalate that is not corrected by diet modification. Low urinary volume does not preclude donation, but donor candidates and those who donate are strongly advised to increase fluid intake to achieve a urine volume >2 to 2.5 L/day.

By comparison, approximately 20 percent of transplant programs exclude all donor candidates with a history of nephrolithiasis, while another 20 percent will accept those with a history of stones if stones are not present.

Increased body mass index (BMI) — The decision to approve donor candidates with obesity (defined as BMI >30 kg/m²) should be individualized based on demographic and health profile in relation to the transplant program's acceptable risk threshold [5]. Studies of United States donors found a stronger association of higher BMI at donation with 20-year postdonation ESKD risk compared with the risk relationship observed in a large meta-analysis of data for healthy nondonors [56,57]. These findings suggest that the implications of obesity for renal risk may greater in the context of hyperfiltration stress to a single kidney. Alternatively, the large number of adjustment covariates may explain the lower adjusted risk of obesity in the study of healthy nondonors.

Assessment of United States registry data from 2010 to 2016 demonstrates substantial center-level heterogeneity in the BMI of accepted donors [58].

Malignancy — OPTN policy requires exclusion of living-donor candidates with active malignancy that either requires treatment other than surveillance or has more than minimal known risk of transmission. However, policy was revised in 2016 to permit transplantation of living-donor organs removed as part of treatment for an individual's health condition (termed "therapeutic donation" by the OPTN) under center-specific written protocols. For example, people with high-grade Bosniak kidney cysts (III or higher) or small (T1a) renal cell carcinoma curable by nephrectomy have served as living kidney donors on a case-by-case basis, with informed consent of the donor and recipient [59-62]. Donation of a kidney with a Bosniak II kidney cyst should proceed only after assessment for the presence of solid components, septations, and calcifications on the preoperative CT scan (or magnetic resonance imaging [MRI]) to avoid accidental transplantation of a kidney with cystic renal cell carcinoma [5]. (See "Simple and complex kidney cysts in adults", section on 'Bosniak classification of kidney cysts'.)

Individuals with a past history of treated cancer with "intermediate" (1 to 10 percent) or higher risk of transmission or recurrence should be excluded from living kidney donation [63,64]. These malignancies include melanoma, choriocarcinoma, hematologic malignancies, monoclonal gammopathy, and testicular, lung, and breast cancers [65].

KDIGO suggests that living kidney donation from people with a past history of treated malignancies with a "low" risk (<1 percent) of transmission or recurrence may be considered on a case-by-case basis with informed consent of the recipient and donor [5,64].

OPTIMIZING EFFICIENCY IN THE DONOR CANDIDATE EVALUATION — The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends transplant programs to conduct as efficient a donor evaluation as possible, meeting the needs of donor candidates, intended recipients, and the transplant program [5]. While this recommendation is ungraded due to the lack of supporting evidence, it is increasingly recognized that avoidable delays can lead to dialysis initiation for preemptive transplant candidates, lengthen dialysis time for those patients on dialysis, reduce donor satisfaction, and, in some cases, lead to donor fatigue and withdrawal from the evaluation processes [66-69]. Opportunities to improve efficiency include the choice, timing, and sequencing of evaluation tests, procedures, and consults; use of navigators; and monitoring of evaluation timeliness as a quality metric [70]. Future efforts to define, collect, and report indicators of an efficient living-donor evaluation, and to inform related quality improvement initiatives, are an important research priority. New evidence suggests that evaluating multiple living kidney donor candidates simultaneously is more cost effective than evaluating them sequentially as it improves the likelihood of timely donor identification [71].

FOLLOW-UP AFTER KIDNEY DONATION — The Organ Procurement and Transplantation Network (OPTN) requires that transplant programs report follow-up clinical and laboratory data on living donors at discharge (or at six weeks after donation, whichever comes first) and then at six months, one year, and two years after donation [72]. Responsibility for the coordination and performance of donor follow-up has raised controversies regarding financial and time burdens on both centers and donors [40]. Monitoring incurs costs and may provide only limited information for the majority of donors who demonstrate stable clinical status and well-being. However, these concerns are outweighed by fundamental ethical principles and the need to improve the evaluation and selection processes and support public trust in donation [73].

We agree with the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guideline that blood pressure measurement, body mass index (BMI) measurement, serum creatinine and estimated glomerular filtration rate (eGFR), and albuminuria measurement should be performed at least annually [5]. A healthy lifestyle (eg, exercise, healthy diet, tobacco abstinence) should be reviewed and promoted.

Follow-up and care may be appropriately performed by a primary care clinician, but a personalized postdonation care plan should be provided before donation to clearly describe follow-up care recommendations, who will provide the care, and how often [5].

The Swiss Living Donor Health Registry (SOL-DHR) provides a model for involvement of clinicians to achieve short- and long-term follow-up of donor health and well-being [74]. Similarly, in Norway, donor follow-ups begin at week 3 to 4, then by month 3, followed by yearly monitoring for five years and every fifth year thereafter. Under a mandate from the Health Services Research Administration, the Scientific Registry of Transplant Recipients is developing a long-term living donor registry in the United States to capture postdonation medical and psychosocial outcomes [75,76].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)

SUMMARY AND RECOMMENDATIONS

●Donor evaluation – The overall purpose of the donor evaluation is to ensure that the donor candidate is in good health, has normal kidney function and structure, is not a risk to the recipient with respect to transmission of infections and malignancy, and will not face known, unacceptable risks after donation. The Organ Procurement and Transplantation Network (OPTN) requirements specify that the following be performed and documented prior to living kidney donation (see 'Donor evaluation' above):

•Blood typing (performed on two separate occasions before the recovery). (See 'Blood typing and crossmatch' above.)

•A medical evaluation (performed by a clinician or surgeon with experience in living donation). (See 'Medical evaluation' above.)

•A psychosocial evaluation (performed by a psychiatrist, psychologist, masters-prepared social worker, or licensed clinical social worker). (See 'Psychosocial evaluation' above.)

•Living-donor recovery hospitals must designate and provide each living-donor candidate with an Independent Living Donor Advocate (ILDA; one person or a team with a key contact) who is not involved with the potential recipient evaluation and is independent of the decision to transplant the potential recipient to ensure that the donor has received information on all phases of the donation process and to advocate for the rights of the donor. (See 'Independent Living Donor Advocate' above.)

●Contraindications – Based upon the initial evaluation, a donor candidate may be accepted, declined, or require additional assessment. The OPTN has defined a number of absolute contraindications to kidney donation. There is also substantial variability across transplant programs concerning relative exclusion criteria for living kidney donation. The decision-making process is nuanced and also incorporates donor autonomy in accepting risks after full disclosure (including recognition of uncertainty) if estimated risks are within a center's threshold of acceptable risks. (See 'Contraindications to living kidney donation' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Anitha Vijayan, MD, who contributed to earlier versions of this topic review.