Kidney Transplantation and Candidate BMI: Viability is in the Eye of the Beholder

Obesity is a growing epidemic in the United States and its prevalence is approximately 42% in adults; with rates of obesity highest in Non-Hispanic Blacks and persons ages 40–59 (1). Rates of severe obesity, defined as body mass index (BMI) greater than 40 kg/m², have doubled in the past 20 years threatening nearly 10% of the U.S. population (1). Likewise, the prevalence of obesity in patients with kidney failure has increased over time mirroring these trends in the general population (2).

Importantly, despite certain risks associated with obesity, transplantation provides a significant survival advantage relative to maintenance dialysis for patients with End-Stage Kidney Disease (ESKD) (3,4). Increased BMI is associated with inferior surgical and medical outcomes in kidney transplant recipients (increased risk of perioperative complications and cardiovascular disease) and transplant programs often impose absolute upper cutoffs to BMI for transplant candidates (5,6). In addition, it is common that potential transplant candidates with high BMI are tasked with weight loss prior to or after placement on the waiting list. In patients with ESKD, it is possible, but challenging to engage in aerobic exercise as a weight loss strategy. This admixed with renal dietary restrictions and the risk of malnutrition with caloric restriction makes weight loss for patients undergoing dialysis dually difficult.

Despite these complex challenges, some programs have the surgical expertise allowing for candidates with high BMI to undergo kidney transplant. In fact, the variation of morbidly obese recipients (BMI ≥ 35 kg/m²) between adult kidney transplant centers is striking. As depicted in Figure 1, based on national SRTR data between 2015 and 2020, approximately 12% of recipients were morbidly obese. However, 14% of centers had <5% of morbidly obese recipients while 11% of centers had >20% of morbidly obese recipients. This heterogeneity of center practices may reflect regional variations of obesity in the population but also likely reflects center protocols and relative contraindications used to assess patient viability.

Figure 1.

Proportion of Morbidly Obese Adult Recipients by Kidney Transplant Center in the United States

Source: unpublished SRTR data from 1/1/2015–12/1/2020 among adult kidney transplant centers

In the current issue of the American Journal of Kidney Diseases, Sureshkumar, et al. performed a paired-kidney analysis to compare outcomes between deceased donor kidney recipients across four strata of BMI (7). They identified 44,560 paired kidney-only recipients over a 16-year time span using the United Network of Organ Sharing database and evaluated death-censored graft failure, delayed graft function, hospital length of stay and patient survival with an average of 3.9 years post-transplant follow up. Importantly, the paired-kidney design minimizes underlying biases in donor quality that may be allocated differently to obese versus non-obese recipients. The primary findings of the study indicated a significantly higher delayed graft function (DGF) rate among obese and morbidly obese recipients but only a modest, and non-statistically significant, difference in graft loss for patients with BMI > 35 kg/m² versus BMI 30–35 kg/m².

The interpretation of these findings should be made in the context of several issues.

BMI is a crude calculation of overall health and ultimately more specific measures are typically needed to determine eligibility for a potentially lifesaving intervention. The limitations of BMI include that it is ill-suited to differentiate muscle mass from fat mass and its distribution (visceral adiposity versus subcutaneous adiposity) and the impact on metabolic health (8). Furthermore, sarcopenia is associated with advanced kidney disease and kidney failure, particularly in older individuals. Therefore, in patients with kidney disease and significant sarcopenia, the risk of missing a diagnosis of obesity using BMI measurement alone is high (9). Thus, other measures of body size are better suited to address these limitations including waist circumference or body surface area.

The authors also used a single, cross sectional BMI value calculated at the time of transplant. This value may not reflect if a candidate lost or gained weight prior to transplantation. Unintentional weight loss in a patient with kidney failure may signal malnutrition from a myriad of other co-morbidities (10). Whereas, intentional weight loss while on the waiting list may result in substantial weight gain post- transplant and not necessarily attenuate other underlying comorbid conditions (11) In addition, the effects of BMI on post-transplant outcome differ by sex, race and etiology among other potential characteristics (12). Overall, the rationale for an absolute BMI cutoff in “lumping” all potential candidates with the same BMI having the same risks does not suitably distinguish viability for transplant and may often exclude patients that can benefit from the procedure.

There are several key points of the study findings that may be important for prospective clinical care, policy and research. Primarily, the study demonstrates that with rigorous methodology accounting for donor quality, the risk of graft failure is relatively comparable between morbidly obese and obese (BMI > 35 kg/m² vs. BMI 30–35 kg/m²) transplant recipients. Thus, transplant opportunities could be expanded for obese patients by relaxing selection criteria based on recipient BMI alone and confer significant survival advantage to these patients. However, it is also notable that DGF rates are significantly higher in the morbidly obese group reinforcing that the surgery may be more complicated and perioperative period more resource intensive. Finally, the barrier in access to care in this population is significantly explained by center variation, suggesting that contraindications differ by center and these data should be clear to prospective patients to understand their viability as a transplant candidate at a given center.

Improving access to kidney transplant for broader population may mean that the kidney community accepts certain post-transplant outcomes (e.g. DGF) as a trade-off for candidates with high BMI. Certainly this may impose cost implications for centers, without reimbursement modifiers, because transplanting patients with high BMI is more likely to lead to longer lengths of stay on average. It may also be necessary to replace the use of BMI as a binary determinant for transplant candidacy without consideration of other patient characteristics, or, alternative markers for metabolic or cardiovascular risk. Hypercholesterolemia, diabetes, and hypertension are well-known complications of immunosuppression medications after transplant and are compounded by obesity. Thus, it is prudent for early recognition of these conditions post-transplant and use of intensive, guideline-based therapies in order to mitigate cardiovascular outcomes. It is important to emphasize healthy lifestyles and behaviors in obese patients both pre- and post-kidney transplant.

These findings in combination with what is already available in the literature warrant further novel investigations to understand the best measure(s) of body composition and metabolic health in patients with kidney failure and kidney transplant. Studies to better understand the most effective means of maintaining a healthy weight among patients in this population. And, in the translational sphere, a more robust understanding of the intersection of metabolic secretions from visceral fat and kidney transplant or even exploration into metabolomics in kidney transplant (13). In addition, further guidance for obese patients for selecting centers with variable thresholds for patients may improve decision-making and expedite access to care for this population. Overall this study is timely given the continued growth of the obese ESKD population and has important implications for prospective research, clinical care and transplant policies.