One of the key steps in determining ways of safely expanding the living donor pool is to better understand current practices in living donor evaluation and exclusion. In our study, nearly half of all prospective donors were excluded. Of the 150 prospective donors excluded for medical reasons, 79% were excluded for obesity (BMI > 30), hypertension, nephrolithiasis, and/or abnormal oral glucose tolerance. At the time of study analysis, 22% of prospective donors were still actively being evaluated and nearly 23% were withdrawn before the evaluation process was complete, most often because the intended recipient was transplanted from a deceased donor or an alternate living donor.
Historically, prospective donors with obesity and hypertension have not been allowed to donate. However, severe organ shortages and long wait-times have increased pressure to consider acceptance of these medically complex donors. In 2005, the median wait-time for kidney transplantation (living donor or deceased donor) in the United States was 3.5 yr (13
). In some regions, however, the wait-times for deceased donor transplantation are as high as 6–8 yr, based on blood type and degree of sensitization. Many patients remain on dialysis during this time, suffering high mortality rates and experiencing significant morbidity. In this study, our objective was to characterize the prospective donor population at a single transplant center and to determine the prevalence of, and reasons for, donor exclusion.
A flowchart of the current living donor evaluation process at our center is presented in and . Although the specifics may differ somewhat among centers across the country, most follow a similar stepwise approach. In cases where the intended recipient has several prospective donors, the most compatible donor (based on histocompatibility, age, and other known comorbidities) is typically evaluated first. The evaluation process begins with prospective donor-initiated contact with the transplant center. Living donor coordinators then complete a phone screening interview sheet that details basic demographics, relation to intended recipient, and key medical and surgical history. Prospective donors with preexisting kidney disease, diabetes mellitus, cancer, cardiovascular disease, or recent history of nephrolithiasis are considered unacceptable and are routinely excluded at this point. Whenever possible, an alternate living donor is then evaluated. Donors with a BMI > 30 kg/m2 are counseled to lose weight and encouraged to contact the center when they reach their target weight. Similarly, donors with an abnormal two-h glucose tolerance test are reevaluated after successful weight loss. Although donors with hypertension requiring antihypertensive medications have been routinely excluded in the past, more recently, we have allowed them to proceed with a clinical visit if the potential donor is (i) strongly motivated to proceed in a setting where no alternative living donor is available, (ii) a first-degree relative or spouse to the intended recipient, and (iii) able to achieve normal blood pressure with a single agent.
Flowchart of living donor evaluation process prior to transplant clinic visit.
Fig. 4 Flowchart of living donor evaluation process at transplant clinic visit. *Further evaluation necessary. #Laboratory studies: complete blood count, comprehensive metabolic panel, ABO and Rh typing, lipid panel, uric acid, phosphorus, PT/PTT, bilirubin, (more ...)
If the phone screening does not reveal a clear contraindication to donation, a transplant clinic visit is scheduled. Prospective donors undergo evaluation by a transplant nephrologist and social worker. In cases where the blood pressure at the visit is >140/90 mmHg, ambulatory blood pressure monitoring is routinely ordered. Prospective donors with a history of nephrolithiasis within the past 10 yr or history of intervention for stones are excluded. Those with asymptomatic stones or calcification found on imaging studies are considered on a case-by-case basis, based on the extent of the stones and comprehensive metabolic evaluation.
Most centers in the United States, including ours, follow the 2007 UNOS guidelines for absolute contraindications (). The evaluation in prospective living donors with one or more relative contraindications, however, can be much more variable. Included in these relative contraindications are grade 1 obesity (BMI 30–35 kg/m2
), kidney stones, and hypertension well controlled on fewer than three medications and without evidence of end-organ damage (14
Although the 2007 UNOS guidelines have set BMI > 35 kg/m2
and evidence of impaired kidney function or proteinuria as absolute contraindications to donation (14
), there is no clear consensus for candidates with BMI in the range of 30–35 kg/m2
without evidence of impaired kidney function. At our center, general practice has been to exclude prospective donors with a BMI > 30 kg/m2
; 56 (12% of all donors, and nearly 40% of excluded donors) donors were excluded on the basis of obesity. The mean BMI in those excluded was 37 ± 5 kg/m2
(range 31–50 kg/m2
). Given the high prevalence of obesity nationwide (and the exceptionally high prevalence in selected regions), prospective donors with grade 1 obesity will likely account for the largest fraction of excluded willing donors in the coming decades. Few studies have explored the long-term effects of donor nephrectomy on kidney function in obese donors. A higher incidence of proteinuria at 13.6 ± 8.6 yr post-transplantation in patients with obesity at the time of donor nephrectomy has been shown (15
). Among the 14 patients with a BMI > 30 kg/m2
, 13 (92%) developed proteinuria/renal insufficiency, compared with only seven (12%) of the 59 patients with a BMI < 30 kg/m2
. A retrospective analysis of patients undergoing donor nephrectomy 5–40 yr earlier did not demonstrate this difference when compared to BMI and age-matched two-kidney controls from the National Health and Nutrition Evaluation Survey (NHANES) dataset (16
). Donors with BMI >30 kg/m2
were found to have a higher incidence of hypertension and dyslipidemia compared with donors with BMI < 30 mg/m2
. Recent studies have highlighted the association between obesity and chronic kidney disease in the general population (17
). Yet unknown is whether the higher incidence of hypertension and/or dyslipidemia will translate to higher long-term cardiovascular mortality and morbidity in this donor population.
Although most centers routinely exclude prospective donors with poorly controlled hypertension and/or evidence of end-organ damage, the decision of whether to exclude donors with well-controlled hypertension, without proteinuria or diminished kidney function, remains controversial. The long-term risks of donor hypertension on the donor and recipient remain unclear. A survey of transplant centers published in 2007 showed that 47% and 41% of centers excluded patients taking any antihypertensive medication or taking more than one medication, respectively (7
). A meta-analysis of living kidney donors examining blood pressure changes post-donation showed that kidney donors may have a 5-mmHg increase in blood pressure within 5–10 yr (19
). However, several of these studies were limited in sample size and duration of follow-up. At our center, prospective donors older than 50 yr of age with a history of hypertension controlled with one to two medications and with normal renal parameters (absence of proteinuria, measured creatinine clearance >80 mL/min/1.73 m2
) are assessed on a case-by-case basis. The decision of whether to proceed with evaluation is based on donor and recipient characteristics (including age, relationship, comorbidities) and the availability of alternate living donors. Of the 484 prospective donors analyzed in this study, 37 (8%) were excluded for hypertension. Additionally, 7/56 (13%) prospective donors excluded for obesity reported coexisting hypertension. Of the 37 prospective donors excluded for hypertension, 24 (65%) were above the age of 50 yr.
Practices in evaluating and excluding prospective donors with a history of nephrolithiasis vary considerably across the United States (6
). Although many centers proceed with transplantation if metabolic evaluation is normal and in the absence of a current stone, approximately 20% exclude all patients with a history of nephrolithiasis. At our center, prospective donors with a history of nephrolithiasis within the past 10 yr, history of intervention for stones, and/or abnormal metabolic evaluation are excluded. In the present study, 10 (2%) prospective donors met at least one of these criteria.
Although centers in the United States routinely exclude prospective donors with diabetes, the evaluation of donors with an impaired fasting glucose, or abnormal two-h oral glucose tolerance test (OGTT), is more variable. Prospective donors with obesity, a family history of diabetes, or a history of gestational diabetes often undergo a two-h OGTT. Most centers exclude patients with a confirmed result >140 mg/dL. Although studies in the general population show that impaired glucose tolerance correlates with an increased risk of diabetes and cardiovascular disease, corresponding data in the living donor pool are not available. In the present study, 15 (3%) prospective donors were excluded because of abnormal glucose tolerance. In the case of glucose intolerance, as with hypertension and obesity, a reluctance to accept a prospective donor relates not only to concerns regarding donor safety but toward recipient survival and allograft function as well.
Prospective donors with dyslipidemia are not excluded from kidney donation. Those with borderline hypertension and not on antihypertensive agents or those with family history of diabetes but normal glucose tolerance tests are also not routinely excluded from donation. Long-term follow-up of such donors remain elusive and questions of whether donation may accentuate metabolic syndrome is unknown. Inclusion of donors with known hypertension, obesity, or impaired glucose tolerance raises the concern of accelerating the clinical sequelae of a metabolic syndrome in these potentially higher risk living donors, leading to a conservative approach to living donor selection in many centers.
Historically, cross-match positivity and ABO-incompatibility have been considered absolute contraindications to donation. More recently, desensitization and kidney-exchange programs have led to the successful expansion of the living donor pool. Roodnat et al. (12
) described a significant increase in the number of living donor transplants in the Netherlands with the initiation of alternative living donation programs. US centers have been participating in paired donor exchange with promising early results (20
). Of the 484 prospective donors analyzed in this study, 35 were excluded based on ABO-incompatibility and 22 were excluded based on positive cross-match results. All prospective donors excluded for these reasons were routinely given information and literature about paired donor network exchange.
There are several limitations to this report. This is a single-center study. Larger multicenter prospective studies are needed to further examine the living donor evaluation process at centers with different size and donor and recipient characteristics. The data for this study were obtained by chart review of our electronic transplant database. Basic demographic information is easily available for all subjects. However, detailed information such as an extensive past medical history was not consistently available. While we could assess the presence or absence of a specific medical condition, we could not necessarily assess its severity. More detailed information is likely available to clinicians and could influence decision-making.
In this study, the majority of prospective living donor candidates were excluded for medical reasons such as obesity (BMI > 30), hypertension, nephrolithiasis, and abnormal oral glucose tolerance test. While these perceived risk factors for long-term morbidity in donors have been applied to protect the donor, definitive evidence of increased long-term risk is still lacking. Recent long-term outcomes studies in healthy uninephric cohorts are reassuring for donors selected using the traditional guidelines for living donor evaluations (21
), and hence, strict adherence to these guidelines better assures the long-term well-being of living kidney donors. However, an overly conservative approach will also prevent a realistic opportunity for kidney transplantation, especially in those ESRD patients who are older, have multiple comorbidities, and only one potential living donor. At our center, we routinely provide follow-up clinical examination in living donors up to two yr after donation that includes measurement of comprehensive metabolic panel, complete blood count, and urine analysis. As many recipients on the waiting list have waiting times far in excess of their life expectancy, the complexity lies in balancing the risks to donors with the potential benefits to recipients. Additional longer-term studies are needed to determine risks in medically complex donors and to better define this balance. Challenges to such analyses include limited access to living donors beyond the first year of transplantation and lack of medical insurance reimbursement for such follow-up. In the meantime, we favor a careful stepwise personalized approach that incorporates characteristics of both the prospective donors and intended recipients.