The National Health and Examination Survey in 2003-2004 indicated that approximately 66% of U.S. adults were either overweight (BMI 25-29.9 kg/m2) or obese (BMI 30-34.9 kg/m2). Obesity is considered a risk factor for the development and progression of certain etiologies of chronic kidney disease (CKD). Impressively, weight loss in the predialysis population either by means of lifestyle modification or surgically mediated weight loss can sometimes halt progression or even improve kidney function. As expected, the prevalence of obesity among patients listed for a kidney transplant has increased significantly. Importantly, there is a general reluctance among transplant surgeons and nephrologists in transplanting obese patients. In the United States, the likelihood of receiving a kidney transplant progressively decreased between 1995 and 2006 with increasing degrees of obesity. To justify this trend and refute any possibility of obesity discrimination, the transplant community must demonstrate any difference in survival between transplantation and maintenance dialysis across degrees of obesity as well as any difference in patient and allograft survival across all levels of BMI. Despite the limitations of retrospective design, large epidemiologic studies analyzing United States Renal Data System (USRDS) and Scientific Registry of Transplant Recipients (SRTR) databases support a survival benefit of transplantation over dialysis in the obese population.

In the setting of a shortage of transplantable kidneys, it is incumbent upon the medical community to allocate this resource so as to maximize the benefit for society at large, and not just
each individual or small cohort of individuals. There is conflicting data in the literature in regard to any adverse effect of BMI at the time of transplantation on patient and allograft outcome. An analysis of 51,927 primary adult kidney transplants in the USRDS database demonstrated a strong association between BMI and both patient and allograft survival at both ends of the BMI spectrum, yet elevated BMI was associated with a worse graft survival independent of patient survival as well as delayed graft function (DGF). In contrast, a more recent analysis of the Australian and New Zealand Dialysis and Transplant Registry assessed the relationship between BMI at transplant and allograft outcomes in 5684 patients transplanted between 1991 and 2004 and did not demonstrate a significant relationship of elevated BMI and inferior patient or allograft survival on multivariate analysis. Furthermore, underweight patients had greater late (≥5 year) death-censored graft loss, which was attributed to greater chronic allograft nephropathy. Nevertheless, it remains unclear whether obesity itself or factors related to obesity are associated with poorer allograft outcomes. In addition, the effect of intentional weight loss in this population in preparation for transplantation remains unknown.

Weight gain is quite common in the posttransplant period. Mean weight gains seem to fall within the range of 8% +/− 10% at 1 year and slightly greater thereafter. The impact of weight changes on patient and allograft survival remains unclear. A retrospective analysis revealed a correlation of poor weight gain and low BMI posttransplant with worse kidney function and a greater incidence of chronic allograft nephropathy. In contrast, two retrospective studies found that patients with better kidney function, measured by the Cockcroft-Gault equation, gained more weight posttransplant. Whether poor weight gain is a marker of other confounding factors associated with either an acute or a chronic inflammatory state and not a direct function of weight itself is unknown. Similarly, it is well-established that weight gain is strongly associated with increased risk of an unfavorable metabolic milieu including hyperglycemia, hypertension, and hyperlipidemia, which are all highly prevalent posttransplantation. Prospective studies are necessary to clarify the correlation between allograft function and posttransplant weight gain as well as what degree of change in weight correlates with worse clinical outcomes.

The stimulus for posttransplant weight gain is thought to be multifactorial (Table 13-1). The impact of immunosuppressive therapy on posttransplant weight gain is of particular interest
because this is one area in which a physician may intervene in an attempt to impact a change in weight. Over the past two decades, patients have classically remained on triple therapy including low-dose prednisone, a calcineurin inhibitor (CNI), and an antiproliferative agent. Many in the transplant community believed that, based on the physiologic effects of excessive exogenous corticosteroid administration, chronic steroid therapy had an adverse effect on new-onset diabetes, hyperlipidemia, and weight gain posttransplant. Beliefs regarding the effect of either CNI or antiproliferative agents, both as a class or individually, remained unclear. A recent retrospective analysis evaluated the difference in posttransplant weight gain over the first 3 years posttransplant in 95 patients treated with standard triple immunosuppression and those with either complete steroid avoidance or early steroid withdrawal. Using a chi-square analysis there was no significant difference among percentage of patients who gained weight after transplantation between groups (p = 0.27). However, the largest retrospective analysis of the association between chronic steroid exposure and posttransplant weight gain, which included 328 patients, found that while all patients gained weight during the first posttransplant year, there was a significant difference between the steroid withdrawal and maintenance steroid group. In light of these studies as well as a few other small retrospective analyses, it appears that posttransplant weight gain is multifactorial and the relative contribution of steroids, if present, is small.

The most common cause of allograft loss in the U.S. is currently death with a functioning graft secondary to cardiovascular diseases (CVD). It is established within the general population that obesity and comorbidities related to increased adiposity increase the risk for CVD and death. While this has not been prospectively confirmed in the kidney transplant population, it is reasonable to speculate that minimizing all modifiable cardiovascular risk factors including obesity in transplant recipients could improve both patient and allograft survival. Strategies to either maintain or lose weight posttransplant include lifestyle modification with caloric restriction and increased physical activity, pharmacotherapy, and surgery. A prospective study to assess the efficacy of a weight reduction program in motivated overweight, obese, and severely obese transplant recipients through lifestyle medication demonstrated less weight gain in the motivated group who met with a healthcare professional for 40 minutes and reviewed a detailed three-day food diary and had anthropometric measurements taken yet received no dietary recommendations. While the group was too small to draw any conclusions, these encouraging findings suggest that simply making patients conscious of their dietary habits and making them aware of weight gain posttransplant without any further active intervention may have a significant impact.

There are few medications currently available in the U.S. approved for weight loss. One such medication, Orlistat, is a reversible inhibitor of pancreatic lipase. Inhibition of this enzyme results in some degree of fat malabsorption and reduced net caloric consumption. Patients must follow a low-fat diet as well, or they will suffer from steatorrhea. While no studies currently exist evaluating
the safety or efficacy of orlistat in the kidney transplant population, a small prospective study was performed in liver transplant patients. As there is evidence in the literature of cyclosporine malabsorption with orlistat, this study exclusively included patients taking tacrolimus. There were no documented cases of rejection with orlistat treatment. While weight did not change with orlistat use, there was a significant decrease in waist circumference following 6 months of therapy. As with all gastrointestinal conditions associated with fat malabsorption, the risk for enteric hyperoxaluria with secondary nephrolithiasis and even nephrocalcinosis remains a concern as well. Formal evaluation of both safety, especially at high doses of orlistat, and efficacy are necessary in the kidney transplant population.

Sibutramine is a serotonin and epinephrine reuptake inhibitor that acts centrally to affect satiety. Efficacy of this agent for weight loss in the general population has been established. The efficacy of sibutramine in the kidney transplant population remains unknown, but one should monitor CNI levels closely with introduction of this medication for weight loss management because both are metabolized by the cytochrome P450 3A4 pathway.

Surgery, either in the form of gastric banding or gastric bypass, remains the most invasive option for weight loss. Case reports and small case series are present in the literature; however, formal documentation of the effect of Roux-en-y gastric bypass on the bioavailability of immunosuppressive agents is lacking. Should it be felt that the morbidity and mortality risk from severe obesity be sufficient to justify the risk of allograft rejection secondary to immunosuppressive malabsorption, the patient must be informed of these risks and serum immunosuppressive drug levels must be followed closely.