Kidney Function

An accurate assessment of predonation kidney function allows physicians to estimate the likely level of residual kidney function that donors would have after donor nephrectomy. Most transplant centers obtain at minimum an estimated GFR (eGFR), although guidelines recommend confirmatory testing either through 24-hour creatinine clearance or radioisotope testing. Despite its limitations, measured creatinine clearance is usually the confirmatory test obtained because isotope testing is more costly, more time consuming, and less readily available. If the 24-hour creatinine clearance is marginal, it is recommended that a nuclear study be performed to ensure adequate kidney function before donation. Although previous guidelines recommended a GFR ≥80 mL/min to proceed with kidney donation, KDIGO guidelines have recommend a GFR ≥90 mL/min/1.73 m ² as the acceptable threshold; most importantly, GFR < 60 mL/min/1.73 m ² is not acceptable. For GFRs that fall between 60 to 89 mL/min/1.73 m ² , KDIGO recommends that the decision to allow donation should be individualized, taking into account the donor age and other clinical risk factors in relation to the transplant center’s risk threshold.

Proteinuria

Proteinuria is usually a sign of renal disease and should be estimated either by 24-hour urine protein excretion or urine protein-to-creatinine ratio. We agree with most guidelines that recommend exclusion of potential live donors with a urine protein excretion of >300 mg/day or >30 mg/mmol on spot protein ratio.

Microscopic Hematuria

Urinalysis and urine microscopy are routinely performed as part of the donor evaluation. Persistent microscopic hematuria, defined as more than 3 to 5 urinary red blood cells per high-power field, can result from many causes, such as infection, glomerular disease, nephrolithiasis, and urothelial carcinoma. To exclude urological disease, investigations can include urine culture, urine cytological testing, imaging of the kidneys and urinary tract through ultrasound or computed tomography (CT) scan, and cystoscopy. If the urological workup is unremarkable, a kidney biopsy should be considered to rule out glomerular disease, which precludes donation with the possible exception of isolated thin basement disease. It is important to distinguish thin basement membrane disease from immunoglobulin A (IgA) nephropathy because progressive renal disease is rarely observed with the former condition but occurs in 15% to 40% of patients with IgA nephropathy. It is important to discuss with prospective donors the additional, albeit small, risk conferred by microhematuria evaluation, in the context of their overall risk and commitment to donate. Although short-term outcomes for donors with persistent microscopic hematuria and no contraindication to donation are reassuring, the long-term outcomes remain to be determined.

Cardiovascular Risk

Cardiovascular risk factors, including assessment for hypertension, diabetes, obesity, hyperlipidemia, tobacco abuse, and family history of early coronary artery disease, should be identified during the initial donor evaluation. Chest x-ray examination and electrocardiogram are also standard. For low-risk donor candidates, further cardiovascular evaluation is not recommended. It is suggested that stress testing should be performed in men aged 50 years or older, women aged 60 years or older, and donor candidates with more than one cardiac risk factor. However, no available evidence exists to support more rigorous cardiac testing than is recommended for nondonors undergoing surgery.

Hypertension

Donors should be screened for hypertension with two or more properly measured seated blood pressure (BP) readings. If there is concern for white-coat hypertension, ambulatory BP monitoring should be performed. Some centers allow for donation in the setting of mild hypertension controlled on one or two agents based on good short-term outcomes in selected donors. Selection criteria of these donors should include absence of end organ damage related to hypertension (left ventricular hypertrophy and retinopathy), absence of proteinuria and microalbuminuria, and normal GFR. The safety of donation under such circumstances has predominantly been studied in Caucasian donors. Available data indicate that hypertensive African American donors should be excluded because of the increased risk for postdonation kidney disease.

Diabetes

Because type 2 diabetes is a major cause of ESRD, most transplant centers do not accept potential donors with glucose impairment or overt diabetes or those with a strong family history of diabetic kidney disease, although it is unclear whether in these settings, donor nephrectomy leads to higher risk for diabetic nephropathy or faster progression of nephropathy. All potential donors should have a fasting plasma glucose, and in those with additional risk factors for diabetes, including first-degree relatives with diabetes, history of gestational diabetes, or body mass index (BMI) >30 kg/m ² , a glucose tolerance test and hemoglobin A1C should be performed. Recently revised American Diabetes Association guidelines should be applied to diagnose diabetes and prediabetes.

Obesity

The majority of transplant centers exclude obese donors with a BMI >35 kg/m ² because of concern that excess weight is a known risk factor for ESRD. Despite this, the rates of obesity in living donors have increased with >25% considered obese at the time of donation. Obesity may be a risk factor for longer postdonation hospital length of stay and increased rates of postoperative wound complications. Although previous studies have suggested that obesity was not a risk factor for postdonation chronic kidney disease, a recent evaluation of Scientific Registry of Transplant Recipients (SRTR) data noted that donor obesity was independently associated with an increased risk for ESRD 20 years after kidney donation. Compared with nonobese living donors, obese donors had a 1.9-fold increased risk for postdonation ESRD. It is prudent to discuss weight loss management strategies and provide informed consent regarding potential short- and long-term risks in obese individuals considering living donation.

Inherited Renal Disease

Potential kidney donors, especially those considering donation to biological relatives, need to be assessed for hereditary kidney disease. It is important to be aware of the cause of the intended recipient’s kidney disease and whether other family members are affected. The most common scenario encountered is a family history of autosomal dominant polycystic kidney disease (ADPKD). If the potential donor is older than age 30 years, renal ultrasound or computed tomography of the abdomen and pelvis is highly sensitive in ruling out cystic disease. In younger donors, genetic testing either by linkage analysis or direct deoxyribonucleic acid should be obtained.

Alport syndrome is a genetically heterogeneous disease with X-linked, autosomal recessive, and autosomal dominant variants, with the majority of cases being X-linked. Persons being evaluated for donation with a family history of Alport syndrome need to be screened for hematuria, hypertension, and hearing and eye abnormalities. Male siblings older than age 20 are unlikely to have the disease if hematuria is absent. Sisters of affected male recipients with X-linked disease have a 50% chance of being carriers; a small percentage of such women carrying the abnormal gene do develop renal failure. If hematuria is present, a kidney biopsy should be performed with immunostaining and consideration of genetic consultation.

Nephrolithiasis

A history of urinary tract stones has historically been a relative contraindication to donation because stones tend to recur and obstruction of a solitary kidney could adversely affect function. Despite this risk, there has been increasing acceptance of donors with a history of nephrolithiasis as long as stones are no longer present and no obvious metabolic abnormalities are identified that would increase future stone risk. Although data have shown no difference in the rate of kidney stones requiring surgical intervention or hospitalization in donors compared with nondonors, more studies are needed to evaluate the outcome of stone formers who donate and to identify those in whom donation may contribute to accelerated loss of kidney function or other stone complications.

Psychosocial Evaluation and Informed Consent

Current policy in the United States dictates that an independent live donor advocate (ILDA) must work with potential donors to ensure that they are informed and understand the process, are appropriately motivated, are free from coercion, and can make decisions autonomously, independent of family members or the intended recipient. The donor should not feel overt pressure or undue anxiety about proceeding and must be allowed to stop the evaluation process at any time. In addition, a careful psychosocial evaluation should be conducted by a social worker or psychiatrist. Significant psychiatric illnesses that would either impair the person’s ability to give informed consent or that might be negatively affected by the stress of surgery are contraindications to living donation. It is important that the donor have appropriate social support to assist in the postoperative period. If there are signs of secondary gain or financial reimbursement, the donor should be excluded from the process.

End-Stage Renal Disease

The overall incidence of ESRD among living kidney donors during the first 10 years after donation is low, with rates of 0.2% to 0.5% reported. Despite this, two studies have suggested that the relative risk for ESRD may be higher in certain populations. A single-center study out of Norway found that 0.47% of donors and 0.07% of nondonors developed ESRD, with all affected donors biologically related to their recipient. In another study performed in the United States comparing living kidney donors to healthy controls, 0.10% of living kidney donors and 0.04% of healthy matched nondonors developed ESRD during follow-up. The incidence of ESRD was noted to be higher among donors aged 60 years and older and African American donors. Although both studies had limitations, it is worthwhile to emphasize that although the absolute risk for postdonation ESRD is low, there may be a slightly higher risk compared with a matched, healthy cohort.

Pregnancy

Multiple studies have found an increased risk for gestational hypertension and preeclampsia after kidney donation in women of childbearing age. This raises some concern because preeclampsia may have long-term renal consequences, including increased prevalence of proteinuria and hypertension. Despite these increased risks, maternal and fetal outcomes are comparable to that of the general population, with most having uncomplicated pregnancies. Because women of childbearing age are the largest group of kidney donors, the effects of donation on postdonation pregnancies should be a routine part of the discussion of risks during the initial donor evaluation. Most centers discourage donation in women with a history of pregnancy-induced hypertension or preeclampsia.

Quality of Life

In general, most studies on quality of life after donation report that the majority of donors experience no change or an improvement, with very few experiencing adverse outcomes, including depression and anxiety. On standardized quality-of-life scales such as the Short Form 36 Health Survey, donor and nondonors have scored similarly, even those donors whose recipients had poor outcomes. Most donors would donate again if given the opportunity.

Long-Term Medical Care

In the United States, United Network for Organ Sharing (UNOS) policy requires that the transplant center must maintain contact with the donor for at least 24 months after nephrectomy. Beyond that, recommendations for future medical care and risk modification for a kidney donor are similar to the general population. After donation, kidney donors should undergo routine checkups with a focus on BP and kidney function. Urinary protein excretion should be measured as part of routine follow-up care. Patients should undergo age-appropriate cancer screening and be counseled on the need for weight control, smoking cessation, and abstinence from excessive alcohol. Emphasis should be placed on avoidance of high-protein diets, protein supplements for body building, herbal medications, and excessive use of nonsteroidal antiinflammatory pain medications, all of which may lead to kidney injury.