Transplants Candidates: How Much Does Size Matter?
Krista L. Lentine, MD, MS
Editor's Note: The author will be speaking about this topic at the National Kidney Foundation 2013 Spring Clinical Meetings in Orlanda, Fla.
Obese individuals often are rejected as renal transplant candidates in large part because of their increased risk for surgical complications and adverse outcomes compared with normal-weight individuals.
Clinicians typically determine whether patients are obese based on their body mass index (BMI), but recent studies provide evidence suggesting that high BMI alone may not be an adequate predictor of post-transplant outcomes.
In addition, the current literature has not defined the limits of body composition that preclude clinical benefit from transplantation compared with long-term dialysis among patients who have passed a transplant evaluation.
BMI and delayed graft function
The use of BMI as a transplant selection criterion is based on numerous studies demonstrating associations between high BMI and adverse outcomes. One such study was conducted by Molnar et al.1, which examined data from the Scientific Registry of Transplant Recipients (SRTR) and maintenance hemodialysis (HD) records from a large U.S. dialysis organization.
The study included 11,836 HD patients dialyzed in 2001-2006 who underwent kidney transplantation by 2007. Compared with a reference BMI of 25 kg/m2, a higher pretransplant BMI was associated with progressively higher risk of delayed graft function (DGF). Those with a pretransplant BMI above 40 had a nearly threefold increased risk of DGF, after adjusting for multiple variables.
Increased risk of cardiovascular disease and graft loss
Obesity also has been associated with an increased risk of graft loss. In a study of 51,927 kidney transplant recipients who had up to 10 years of follow-up, death-censored graft loss risk was increased modestly among those with a BMI below 18, but was highest among morbidly obese patients2.
Recipients with a BMI above 36 had a 50% greater adjusted relative risk of graft loss compared with recipients who had a BMI of 24-26. Additionally, a study of 2,067 kidney transplant recipients in the Netherlands found that a BMI above 25 and above 28 were independently associated with an increased risk of graft loss and patient death compared with a BMI of 22-25.3
Furthermore, studies have demonstrated increased cardiovascular risk in obese renal transplant recipients. For example, a study of 1,107 kidney transplant recipients at a single center4 found that each 5-unit increment BMI was associated with a 19% increase in the risk of the cardiac composite outcome of congestive heart failure, atrial fibrillation, and myocardial infarction.
BMI an unreliable predictor?
Although studies have demonstrated the higher risks associated with elevated BMI, some studies have raised questions about the validity of using BMI for transplant candidate selection. Some data suggest that obese patients selected for transplantation may gain clinical benefits compared with remaining on dialysis.
Contributing to some of the controversy is the concept of “reverse epidemiology,” which refers to the apparent survival benefit that high BMI confers to dialysis patients. In a historical cohort study of 151,027 patients who started renal replacement therapy in the U.S. in 1995-1997, obese patients had an unadjusted two-year survival of 68% compared with 58% among non-obese patients.5
An analysis of the Dialysis Outcomes and Practice Patterns Study database for European HD patients in 1996-2000 found that a BMI below 20 was consistently associated with the highest relative death risk.6 Compared with dialysis patients who had a BMI of 23-24.9, those who were overweight (BMI 25-29.9), obese (BMI 30-34.9), and morbidly obese (35-39.9) had a 16%, 27%, and 24% decreased risk of death. The apparent protective effect of higher BMI in dialysis patients is explained in part by underlying comorbidities and malnutrition, both of which decrease BMI and increase mortality risk.
Emerging evidence suggests that this reverse epidemiology may not be present in all subgroups. For example, a recent study that followed adult dialysis patients from the first dialysis treatment until seven years, death, for kidney transplant found that while older dialysis patients had reverse epidemiology for BMI, younger patients with a high BMI had 1.7 times the standardized mortality of younger patients with normal BMI, which reflect typical general population patterns.7
Importance of muscle mass
Recent studies have suggested that BMI is an imperfect measure of adiposity. For example, Beddhu et al.8 found that the protective association of high BMI with survival on HD is limited to patients with normal or high urinary excretion of creatinine, which is considered a marker of muscle mass. In contrast, dialysis patients with a higher BMI, low muscle mass based on urinary creatinine values, and thus inferred high body fat, had significant increased mortality compared with patients who had a normal BMI. Streja et al.9 examined associations of markers of pretransplant weight and muscle mass with mortality in transplant patients using an integration of SRTR registry data with maintenance HD records for 10,090 patients who underwent transplantation in 2001-2007.
The study, which considered BMI a measure of weight and serum creatinine a measure of muscle mass, found that a BMI above 35 was associated with an increased risk of graft failure in adjusted analyses, but that this association was not significant after adjusting for multiple variables, including case mix, markers of malnutrition-inflammation complex, and transplant factors. Patients with high pretransplant serum creatinine—and thus inferred high muscle mass—had reduced risk of graft failure, whereas those with a low pretransplant serum creatinine had increased risk of graft failure.
The researchers concluded that pretransplant obesity does not appear to be associated with poor post-transplant outcomes, but larger muscle mass, as reflected by higher serum creatinine, is associated with graft and patient survival advantages. Pending additional studies, the authors “caution against categorical recommendation of weight loss to apparently obese dialysis patients as a requirement for transplant wait-listing.”
A recent study of 993 kidney transplant recipients in Budapest10 also has raised doubts about the value of BMI alone for predicting post-transplant outcomes. The study found no clear association between BMI and long-term mortality, but when adjusted for waist circumference—which is a measure of abdominal fat—patients with a high BMI had lower mortality compared with patients who had normal and low BMI. Large waist circumference was associated with increased mortality risk, an association that was more pronounced after adjusting for BMI.