EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: To satisfy donor organ shortage, overweight and obese donors are becoming a greater proportion of the kidney donor pool. Although good safety data exist in overweight and moderately obese individuals (body mass index = 25 to 35 kg/m²), there is little information about outcomes in morbidly obese donors (body mass index ≥ 40 kg/m²). The purpose of this study was to review the experience with morbidly obese donors in a single center and assist in the discussion about the feasibility of nephrectomy in such cases.

Materials and Methods: Outcomes of nephrectomy in morbidly obese donors between January 2005 and June 2010 were reviewed retrospectively and compared with outcomes in nonobese donors.

Results: Of 386 nephrectomies, 7 involved morbidly obese donors. Mortality and major complication rates were low in all body mass index categories. A high incidence of minor postoperative complications was observed in the morbidly obese, with 57% morbidly obese patients requiring treatment for complications including respiratory infection, compared with 30% in nonobese donors (P < .05). There were no significant differences in mean operative time, estimated blood loss, and length of hospital stay between all body mass index categories. Limited follow-up data (mean, 20 mo) showed similar renal function parameters between groups.

Conclusions: The limited data suggest that nephrectomy may be feasible in selected morbidly obese donors. Further study is needed before major conclusions can be made.

Key words : Live donor, Kidney, Obesity, Transplant

Living-donor kidney transplant is the treatment of choice for end-stage renal disease.^{1, 2} The incidence of end-stage renal disease in the general population is increasing, and more candidates are deemed suitable for transplant because of advances in the field. Although the demand for transplant is increasing, the annual number of available deceased-donor kidneys is constant.³ Living-donor transplant programs are crucial to improve the shortage of organ availability and may have better long-term graft and patient survival outcomes compared with deceased-donor transplant.⁴ In the previous year, there were 1667 deceased-donor and 1020 living-donor transplants performed in the United Kingdom. The waiting list for transplant currently stands at 6871 individuals, only a 4% reduction compared with the previous year, and is evidence that the donor pool should be expanded.³

To increase the number of living donors, the feasibility of expanding the donor criteria is being considered, to include individuals previously deemed unsuitable. Donor obesity is considered a relative contraindication but is compatible with acceptable donor and graft outcomes in most cases.^5-9 United Kingdom guidelines support the practice of using otherwise healthy overweight and moderately obese donors (body mass index [BMI] = 25 to 35 kg/m²). Guidelines have been modified recently for very obese status (BMI ≥ 35 kg/m²) from being an absolute contraindication, and very obese potential donors are “discouraged” but not prevented from donating.⁶ However, data are limited about the safety of kidney donation in very obese individuals, and it is not known when an otherwise healthy potential donor may be too obese to be considered for surgery.

Living-donor nephrectomy is a safe procedure, with an estimated mortality of 0.03%.⁷ Although careful donor selection is essential to ensure these levels of safety, stringent selection guidelines also may limit the scarce organ pool. It is important that surgery on healthy donors, without conferring on them a health benefit, should cause minimal harm. It also is important that donors often have great psychological reward from the opportunity to drastically improve the quality of life of a partner, relative, friend, or stranger, and some individuals find it extremely distressing when they are deemed unsuitable to donate.

Obesity is associated with increased risk of impaired long-term renal function. Therefore, transplant teams and potential donors have a very difficult decision. With obesity increasing in the general population, such decisions must be made with increasing regularity. Obese donors now comprise 22.6% living-donor nephrectomies performed in some Western countries.⁷ However, limited data are available about nephrectomy in morbidly obese donors (World Health Organization Class III, BMI ≥ 40 kg/m²).

The purpose of this study was to review the experience of our center about perioperative and long-term outcomes in obese living donors, to facilitate clinical decisions about accepting donor kidneys from obese individuals. We performed comparisons of outcomes between obese donors and donors having lower BMI.

Materials and Methods

From January 2005 to June 2010, there were 383 living-donor nephrectomies performed at West London Renal and Transplant Centre. There were 7 living-donor nephrectomies (2%) that involved morbidly obese donors (morbidly obese group, BMI > 40 kg/m²). Living-donor nephrectomies were analyzed and compared between the morbidly obese group, a nonobese reference group (20 kg/m² ≤ BMI < 25 kg/m²), and an overweight and obese group (25 kg/m² ≤ BMI ≤ 40 kg/m²). All protocols were approved by the ethics committee of the institution before the study began, and the protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration. Written, informed consent was obtained from all patients.

Demographic data were collected for all donors including sex, age, ethnicity, and BMI. Donor selection and acceptance for nephrectomy were guided by clinical and ethical decisions made by the transplant team, based on the prevailing standard of care, not by the study procedure. The team included transplant surgeons, nephrologists, nurse specialists, and anesthesiologists who received guidance from the medical ethics division. No firm rule about the degree of obesity was an absolute contraindication for donation at this organization, and each case was treated individually, considering several preoperative assessment outcomes. All potential donors received rigorous evaluation including blood pressure measurement; physical examination; extensive laboratory testing including hemoglobin A1c, fasting blood glucose, lipid profile, full blood count, serum creatinine, 24-hour urinary protein, urinalysis, and virology and infection screens; imaging including magnetic resonance angiography; cardiorespiratory testing including exercise tolerance tests; and psychological assessment. Exclusion criteria were not fixed, but were determined on an individual basis, and included age < 18 years, renal disease, major cardiac disease, viral infections, substance abuse, and psychiatric illness. All nephrectomies were performed using the hand-assisted mini-open nephrectomy technique, as previously described.^{10, 11}

After the immediate in-patient recovery period, regular follow-up was arranged at 6 months and 1 year after nephrectomy, and then annually thereafter. The follow-up clinic protocol for the donor included a complete history, physical examination (including weight and blood pressure), psychosocial assessment, and laboratory investigations (including renal function tests and glomerular filtration rate [GFR]). Newly developed conditions, such as diabetes and hypertension, were noted and evaluated.

We analyzed 2 sets of primary outcomes: perioperative and postoperative follow-up measures. Perioperative measures included intraoperative time, estimated intraoperative blood loss, length of hospital stay, incidence of surgical complications, and mortality. Follow-up measures assessed the effect of nephrectomy on postoperative donor renal function. We analyzed and compared preoperative and postoperative blood pressure, GFR, creatinine clearance, and proteinuria. The 4-variable modification of diet in renal disease (MDRD) equation, which provides a consistent estimate of GFR across BMI groups, was used in the calculation of GFR.¹²

Data analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 18.0, IBM Corporation, Armonk, New York, USA). Group data were compared using nonparametric tests including the Mann-Whitney U test. Data for the follow-up were compared using repeated measures analysis of variance when sphericity was met. Data are reported as means ± standard deviation (SD), and statistical significance was defined by P < .05.

Of 383 cases analyzed, 337 patients met the inclusion criteria and fell within the defined BMI categories. Mean age at donation was similar for all 3 groups (Table 1). Men comprised a larger proportion of the morbidly obese group than the other groups (Table 1). Consistent with our goal to offer nephrectomy in morbidly obese donors who were otherwise healthy and had normal renal function, no morbidly obese donors had preoperative hypertension (Table 1). Serum creatinine levels and GFR were similar between the 3 groups (Table 1). Intraoperative parameters and length of postoperative hospital stay did not differ significantly between the morbidly obese group and the other groups (Table 2).

No deaths or instances of reoperation were encountered (Table 3). A higher incidence of minor postoperative complications was observed in the morbidly obese, with 57% morbidly obese donors requiring treatment for complications including respiratory infection compared with 30% nonobese donors (P < .05). Pneumonia was the most frequent postoperative complication (Table 3), but no donors required ventilatory support and all recovered without sequelae. There was 1 donor who had wound site cellulitis that resolved with a brief course of antibiotics, and another donor had prolonged wound site discomfort at 12 months after surgery.

Mean length of donor follow-up was 20 months in the morbidly obese group. All groups experienced a significant postoperative decrease in MDRD estimated GFR and increase in serum creatinine, with a gradual return toward preoperative levels during the subsequent months (Table 4). Repeated measures analysis of variance confirmed this within group variation, but the variation between the study groups was not significant; although all groups experienced changes in renal parameters during follow-up, the pattern of change was similar for all groups. These relationships are illustrated by Figure 1. At 1 year after surgery, mean MDRD estimated GFR was significantly lower in the morbidly obese group than the other groups (P < .01), but at 2 years after surgery, mean MDRD estimated GFR was not different between all groups, with an increase toward preoperative values (Table 4).

Mean systolic and diastolic blood pressure were similar between obese and nonobese donors before and after nephrectomy (Table 4). None of the donors in the morbidly obese group developed hypertension or proteinuria during follow-up. There was 1 woman donor in the morbidly obese group who developed non–insulin-dependent diabetes mellitus at 36 months after nephrectomy.

The present study is limited in allowing firm conclusions about the feasibility of using kidneys from morbidly obese potential donors, but it may open discussion and stimulate further work. The finding that the morbidly obese group had an increased frequency of respiratory complications is important, and may be considered when informing potential donors of the risks. However, donors in the obese group had similar hospital stay as nonobese donors, without long-term compromise to respiratory function. These perioperative findings are consistent with results from other authors who evaluated obese donors.⁵ Surgical mortality and major morbidity after nephrectomy was not associated with obesity in the present and previous work.⁷

Several studies have shown that renal parameters, including GFR and proteinuria, are significantly affected after unilateral nephrectomy, with 40% reduction in GFR.^{13, 14} These changes in renal function parameters follow a similar pattern across BMI groups, and the percentage change from baseline is not significantly different between groups.¹⁴ Similar conclusions can be drawn from the present data about morbidly obese individuals, and this expands the scope of previous work to include the extremes of BMI.

Important considerations in renal transplant include the clinical relevance of the changes in renal parameters after nephrectomy and the effect of these changes on obese subjects compared with nonobese subjects. Many kidney donors, obese or nonobese, have a fall in GFR < 60 mL/min/1.73m² and may be classified as having chronic kidney disease.^{15, 16} However, the clinical importance of GFR < 60 mL/min/1.73m² in a patient with a single healthy kidney may not be equivalent to a similar GFR in a patient with 2 diseased kidneys.¹⁶ After the initial decline of GFR after nephrectomy, the processes of renal hypertrophy and other compensatory mechanisms are not well understood. Despite the effects of unilateral nephrectomy on renal parameters such as GFR, numerous long-term follow-up studies have shown that clinical outcomes are encouraging, and comparable to studies in patients who have 2 kidneys.^{7, 17, 18} The incidence of end-stage renal disease is similar in obese patients and the general population.¹⁹ Blood pressure is lower in donors than the general population.²⁰ Kidney donors live longer than people in the general population, most likely because of the rigorous selection criteria and follow-up.²¹

Obesity is associated with increased risk of developing hypertension, heart disease, hypercholesterolemia, and insulin resistance. Chronic kidney disease may further contribute to the risk of developing these clinical problems. Therefore, it would be reasonable to hypothesize that nephrectomy in patients with both obesity and chronic kidney disease would be too risky. However, nephrectomy does not have poor clinical prognostic outcomes in nonobese donors. The increase in the incidence of hypertension and other cardiovascular risk factors in obese donors may be attributed to obesity alone, and may not be exacerbated further by nephrectomy.⁸

Although obese donors may account for > 20% living-donor nephrectomies in some countries, there is a paucity of data about outcomes after nephrectomy in obese donors, especially the morbidly obese.²² The present study of unilateral nephrectomy in subjects with BMI > 40 kg/m² adds valuable data in the ongoing effort to assess the safety and feasibility of kidney donation in these individuals.

Limitations of the present study include the small sample size and limited follow-up, which may limit the assessment of the incidence of cardiovascular, diabetic, and other complications. The small sample size also limits within group comparisons of the effect of demographic characteristics, including age, sex, and race, and limits the potential to generalize the significance of the results. The use of standardized multicenter data will be essential in performing studies with larger donor groups. In addition, it is difficult to determine the effect of the institutional learning curve, but all surgery was done by 3 surgeons, all having many years of experience in this procedure. Furthermore, the study did not evaluate the effect of organs from morbidly obese individuals on the recipient outcomes. Organs from marginal donors may be associated with poorer recipient outcomes.²² Although all grafts from the obese group continue to function, the effect on the recipient was beyond the scope of this study.

In summary, clinicians have difficult clinical and ethical decisions when considering potential obese kidney donors. Donors are counseled, based on current international and local data, before undergoing a procedure with some potential risk. The results of the present study may stimulate the development of larger, multicenter studies to evaluate the potential to expand the organ donor pool and guide future donor selection policy.

Volume: 10 Issue: 6 December 2012

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