Objectives: Renal transplant is the criterion standard treatment for patients with end-stage renal disease. Because obesity rates are increasing in the global population, international standards on renal transplant in obese patients remain a gray area. The aim of this study was to determine whether renal transplant remains the treatment of choice in an obese patient with end-stage renal disease.
Materials and Methods: We performed a retrospective analysis on all patients who underwent renal transplant in our transplant unit between January 2008 and December 2013. Patients were divided into 3 cohorts based on body mass index (cohort A was < 25 kg/m2, cohort B was 25-29.99 kg/m2, and cohort C was ≥ 30 kg/m2). Postoperative complications within 90 days after transplant were assessed using one-way analysis of variance and chi-square distribution. Patient and graft survival rates over 3 years were assessed with Kaplan-Meier analyses.
Results: Of 610 total patients, 92 patients (15%) were classified as "obese" (≥ 30 kg/m2) in cohort C, with 294 patients in cohort A and 224 patients in cohort B (24 patients were excluded). Regarding short-term complications during the 90-day posttransplant period, obese individuals were at increased risk of a higher number of complications (P = .039 for cohort A vs cohort C). Lymphocele in particular was associated with obesity (P = .004); fortunately, this condition had no direct impact on the graft itself and was relatively easy to monitor and treat. The long-term outlook (3 years) appeared positive, with both graft survival (92% in cohort A, 91% in cohort B, and 94% in cohort C) and patient survival (97% in cohort A, 99% in cohort B, and 97% in cohort C) being independent of patient obesity.
Conclusions: Increased body mass index up to 37.5 kg/m2 was not associated with increased risk of serious postoperative morbidity or mortality after renal transplant. Surgery should be considered as the criterion standard treatment for obese patients with end-stage renal disease if they are otherwise medically fit with few or well-controlled comorbidities.
Key words : Graft survival, Patient survival, Transplant outcomes
Renal transplant is considered as the criterion standard treatment for individuals with end-stage renal disease (ESRD). However, it remains controversial whether obesity in the recipient, defined as body mass index (BMI) ≥ 30 kg/m2, influences the rate of postoperative complications and the long-term success of renal transplant. In the United Kingdom, the Renal Association,1 in alignment with British Transplant Society guidelines, stated that, although "obese patients present technical difficulties and are at an increased risk of postoperative complications, obesity is not an absolute contraindication to transplantation." Globally, BMI selection criteria varies across renal transplant centers,1,2 with some drawing a hard line regarding BMI despite evidence that some obese patients have achieved good outcomes after transplant.3
The fact that the global population is both aging and increasing in average BMI4 is concerning for the outlook of any chronic disease, but there is already an established link between end-stage renal failure and obesity. A review in the United States showed that obesity rates in kidney recipients at the time of transplant doubled between 1987 and 2001.5 As of 2011, 23% of US kidney recipients were classified as obese,6 which is significantly higher than the World Health Organization estimation of global obesity at 13% in 2014.7 The main aim of renal transplant is to increase both patient survival and quality of life. Here, our key objective was to determine whether renal transplant should be considered the criterion standard treatment in obese patients with ESRD.
Materials and Methods
We conducted a retrospective analysis on all patients undergoing renal transplant at St. George's University Hospitals NHS Foundation Trust between January 1, 2008 and December 31, 2013. From a total of 634 transplant patients, 610 met the minimum data requirements for this study and were divided into 3 final cohorts based on their BMI values. Cohort A contained all patients with low to normal BMI of less than 25 kg/m2. Cohort B contained all patients classified as "overweight" but not obese, with BMI ranging from 25 to 29.99 kg/m2. Cohort C contained all patients classified as "obese," having BMI greater than or equal to 30 kg/m2.
We reviewed data for each patient to check for postoperative surgical complications during the first 90 days, which is a standard period used for general monitoring.8,9 To monitor long-term graft survival and patient survival, clinical notes were reviewed up to 3 years after transplant. Data collection was carried out with ethical approval from the local institutional research committee, and all protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration. Because this was an anonymized retrospective study, patient consent was not required.
The statistical significance between BMI and number of postsurgical complications per patient was determined using a one-way analysis of variance with Bonferroni adjustment to account for unequal class sizes. Because of the retrospective nature of this study, a further assessment of potential confounding factors was carried out using an analysis of covariance. The statistical significance between BMI and specific type of surgical complication was determined by chi-square analysis. Graft and patient survival analyses were reviewed using Kaplan-Meier curves. For differences in survival, a log-rank test was used. A probability of less than .05 was considered significant.
The total sample size was 610 recipients after 24 patients were excluded due to incomplete data (Table 1). The sample included 6 "underweight" patients (BMI of < 18.5kg/m2) and 6 "moderately obese" patients (BMI of 35-39.99 kg/m2). No patients were "morbidly obese" (BMI of ≥ 40 kg/m2).
Based on our population (Table 1), the typical renal transplant candidate was an overweight 50-year-old male patient (65% total) with hypertension (72% total) looking to be transitioned from hemodialysis (50% total) to a deceased-donor kidney transplant (55% total). Unsurprisingly, the most common comorbidity across all cohorts was hypertension. However, diabetes had a strong link to obesity in patients with end-stage renal failure, with 25% prevalence across cohort C versus a total sample prevalence of 12%.
We observed a significant association between the number of postsurgical complications and obesity, which was confirmed using one-way analysis of variance (F statistic = 3.89; P = .021). Two-tailed t tests assuming unequal variances verified the multiple comparisons and proved the significant difference for patients with a low or normal BMI in cohort A versus obese patients in cohort C (P = .039, using Bonferroni corrected for unequal class size). The individual analysis of covariance assessments, which evaluated each patient demographic as a confounding factor (Table 2), indicated that transplant type, method of preoperative dialysis, presence of heart disease, and age did not affect variabilities in number of complications. However, BMI showed the greatest influence (based on type III sum of squares). Statistical assessment of specific types of posttransplant complications using chi-square analysis (Table 3 and Table 4) found a significant association between obesity and lymphocele (chi-square = 10.9; P = .004). Complications related to intrinsic allograft function (transplant renal artery stenosis and delayed graft function), which could significantly affect long-term transplant outcomes, showed no established link with obesity.
Long-term survival analysis
Graft survival at 3 years was 92% for cohort A, 91% for cohort B, and 94% for cohort C using censored data. Therefore, there does not appear to be any link between graft survival and BMI (Figure 1). Patient survival at 3 years was 97% for cohort A, 99% for cohort B, and 97% for cohort C using censored data. Therefore, there does not appear to be any link between patient survival and BMI (Figure 2).
Body mass index is known to have various deficiencies when used as a measure of obesity because it is an indirect measure of body fat compared with more direct approaches, such as bioelectrical impedance.10 Moreover, BMI does not account for age, sex, or muscle mass. However, BMI is recognized as a good gauge of body fat when applied to the majority, and our local population of transplant candidates is even less likely to lie at the extremes of age or muscularity. Other quick and inexpensive methods such as waist circumference and waist-to-hip ratio become less accurate in more overweight individuals due to varying body fat distribution.11 More accurate methods of obesity assessment, such as densitometry, are too expensive and complex to be considered. Therefore, for our investigation, BMI sufficed as a measurement tool of obesity.
In our review of short-term complications within the first 90 days after transplant, we investigated outcomes in patients with BMIs ranging from 14 to 37.2 kg/m2. A patient with a higher BMI is more likely to have a higher number of postoperative complications than a patient with a "normal" BMI. In a recent report by Tran and associates,12 the renal transplant complications associated with high BMI included wound infection, delayed graft function, and lymphocele. Although a clear trend has been identified between BMI and number of complications per patient, the only statistically significant complication found in our population that correlated with higher BMI was lymphocele (Table 3). Of importance, we did not identify any complications linked to obesity that affected the graft directly.
Long-term outcomes were reviewed for up to 3 years. When we viewed both graft survival and patient survival over 3 years after transplant, we found no direct relation between survival and BMI. In our analyses of both graft survival and patient survival rates, the proportion of patients lost to follow-up at 3 years was markedly lower for obese patients. This could be due to an enhanced effort to follow-up from the medical team, perhaps due to BMI but also perhaps due to the higher rate of comorbidities associated with higher BMI.
The most extreme World Health Organization classification of obesity is the label of "morbid obesity," for which BMI is greater than or equal to 40 kg/m2. Over our 6-year investigative period, no patients in this category were accepted for transplant. However, we can assume the presence of significant comorbidity in these patients, as BMI has not been used as an absolute contraindication. Renal transplant in the morbidly obese remains a controversial subject due to the general paucity of data. However, in a study of 458 patients, Glanton and associates13 concluded that the benefit of deceased-donor renal transplant did not apply to patients with BMI ≥ 41 kg/m2. In the United Kingdom, the Renal Association stated that patients with BMI > 40 kg/m2 are less likely to benefit1 regardless of comorbidity. In the United States, transplant centers have individual guidelines, but many place a hard cut-off at BMI > 35 kg/m2 and even refuse to place these patients on wait lists until they have lost enough weight.14 Weight reduction in these potential transplant candidates is becoming a serious issue, as it can lead to prolonged wait times and a higher rate of mortality on dialysis.15 The physical and nutritional restrictions of having both ESRD and morbid obesity make intentional weight loss difficult, and 2 clear approaches are emerging. Pretransplant bariatric surgery is becoming a more popular option, with excess weight loss at 1 year estimated at 50% to 60%,12 reducing both wait times and expected complications for the transplant itself. However, the University of Maryland Medical Center, one of the largest renal transplant centers in the world, has recognized this difficult situation for patients and is choosing to consider transplant procedures in patients with BMI up to 45 kg/m2.16
Therefore, in conclusion, for the population of patients with ESRD and BMI up to 37.5 kg/m2, renal transplant can be considered the criterion standard treatment as long as medical issues and anesthetic fitness are satisfactory. Postoperative lymphocele was particularly associated with higher BMI, and this should be highlighted in the consenting and monitoring practice. For patients with BMI above 37.5 kg/m2 or who have significant comorbidities, the decision should be taken on a case-by-case basis with consideration of an appropriate weight-loss strategy ranging from lifestyle modification to bariatric surgery.
Subsequently, following on from the analysis within this study, our renal transplant unit has now increased the BMI cut-off from 30 kg/m2 to 40 kg/m2, depending on patient fitness on a case by case basis.
Volume : 17
Issue : 1
Pages : 37 - 41
DOI : 10.6002/ect.2017.0167
From the 1St. George's University of London and the 2St.
George's University Hospitals NHS Foundation Trust, London, United Kingdom
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Abbas Ghazanfar, Renal Transplant Unit, St George's University Hospitals NHS Foundation Trust, Blackshaw Road, Tooting, London SW17 0QT, United Kingdom
Phone: +44 20 8725 2626
Table 1. Demographic and Clinical Characteristics of All Patients (N = 610) Who Underwent Renal Transplant from January 2008 to December 2013
Table 2. Analysis of Covariance Assessments of Potential Confounding Factors Versus Body Mass Index for the Number of Postsurgical Complications Per Patient
Table 3. Analysis of Type of Postsurgical Complication
Table 4. Relationship Between Type of Postoperative Complication and Body Mass Index Class
Figure 1. Kaplan-Meier Curves of 3-Year Graft Survival After Renal Transplant Across Body Mass Index Cohorts (Censored Data)
Figure 2. Kaplan-Meier Curves of 3-Year Patient Survival After Renal Transplant Across Body Mass Index Cohorts (Censored Data)