Clinical outcomes in elderly kidney transplant recipients are related to acute rejection episodes rather than pretransplant comorbidity. Transplantation 87: 1045–1051, 2009 Heldal KA, Hartmann, Leivestad T, Svendsen MV, Foss A, Lien B, Midtvedt K
The population of patients who have ESRD and are older than 65 yr now outnumbers those who are younger than 65 yr. In fact, the number of patients who started dialysis over the age of 80 nearly doubled from 1996 (n = 7054) to 2003 (n = 13,557) (1). Who and when to refer the senior and elderly population presents a challenge to the community of nephrologists who care for them, both while on dialysis and in advanced stages of chronic kidney disease. Existing data suggest that, once they undergo transplantation, older patients actually do quite well from both a quality- and a quantity-of-life perspective (2). The natural consequence of aging, especially with chronic kidney disease, is the accumulation of an increasing burden of comorbidities, cardiovascular and cerebrovascular disease in particular.
This study attempted to ascertain risk factors that were useful in predicting transplant outcome in patients as they advanced in age. The researchers used robust retrospective data from the Norwegian Renal Registry and reviewed all patients who underwent transplantation at a single hospital from 1990 through 2005 with follow-up data available until May 1, 2008. Patients were grouped into three categories: Elderly (≥70 yr; n = 354), senior (60 to 69 yr; n = 577), and control (45 to 54 yr; n = 563) and included only first kidney transplant recipients. A standard Cox model approach (analysis using univariate and forward stepwise regression) with end points of death, death-censored graft loss, or uncensored graft loss was used to assess patient and graft survival. Comorbidity at the time of transplantation was assessed retrospectively using the Charlson Comorbidity Index, a tool considered to be a robust index of comorbidity in transplant patients (3). Data were also collected for immunosuppressive therapy (initially azathioprine, steroids, and cyclosporine; subsequently basiliximab with mycophenolate mofetil, cyclosporine, and steroids), pretransplantation wait time, tissue matching, and acute rejection.
Findings.
Most remarkably, the comorbidity index was not predictive of outcome in the elderly population but did reach significance in all other groups: The hazard ratio (HR) for the elderly was 1.05 (95% confidence interval [CI] 0.98 to 1.12), for seniors was 1.17 (95% CI 1.08 to 1.27), and for control recipients was 1.33 (95% CI 1.19 to 1.48). Important factors that did have a statistically significant impact on transplant outcome in the elderly included early acute rejection (hazard ratio 1.74; 95% CI 1.34 to 2.25), previous time on dialysis, and advancing age. Other independent predictors of death-censored graft loss included delayed graft function and positive anti-HLA antibodies.
Commentary.
Several intriguing aspects of this retrospective study deserve attention. First, the period during which this analysis was performed was associated with considerable advances in the management of many comorbid conditions, and information regarding specific strategies for cardiovascular disease in particular are lacking. Second, demographic review of the elderly population reveals a diabetic nephropathy incidence of only 4%, a median of 14 mo on dialysis before transplantation, and a median cold ischemic time of 13 h. This population is very different from that found in most dialysis units in the United States and other programs worldwide. A selection bias may explain many of the seemingly reassuring findings of this study, such that elderly patients who do not have ESRD from diabetes and have short wait times and donor kidneys in good condition are likely to do well. What remains to be defined is the optimal pretransplantation management and choice of immunosuppressive agents. Evaluation and correction of potential ischemic cardiac and cerebrovascular risk in the elderly is unclear. Finally, aggravation of diabetes and hypertension with steroids and calcineurin inhibitors may also have significantly greater negative impact on both quantity and quality of life in the elderly after transplantation.
Footnotes
Published online ahead of print. Publication date available at www.cjasn.org.
- Copyright © 2009 by the American Society of Nephrology
Graft and patient survival in kidney transplant recipients selected for de novo steroid-free maintenance immunosuppression. Am J Transplant 9: 160–168, 2009 Luan FL, Steffick DE, Gadegbeku C, Norman SP, Wolfe R, Ojo AO
Steroid-free immunosuppression after kidney transplantation has assumed front-and-center attention among both transplant centers and potential recipients, many of whom specifically request such a strategy during their pretransplantation evaluation. Nephrologists are aware of the success of many with this strategy but also are acutely aware of the disastrous outcomes that can occur in a setting in which we do not know exactly who is able to do well without steroids. Indeed, the culture change in transplantation with regard to steroids has been remarkable in light of the fact that they have been the mainstay of immunosuppressant and rejection therapy during the past 50+ years of the modern renal transplantation era. The major potential advantages of improved metabolic outcomes (1), bone health, and cosmetic appeal are only a few of the potential advantages presenting themselves with steroid-free regimens.
The accumulating evidence with both retrospective and smaller prospective studies has suggested promising results with a complete steroid avoidance approach, a rapid withdrawal to “steroid-free” after a short period, or what is now considered the conservative approach of steroid minimization. The advent of immunosuppressive agents against various steps in the pathway of acute rejection has smoothed the road to development of this strategy, as has the increasing experience with potent induction therapy with drugs such as thymoglobulin. Finally, aggressive funding of research into steroid avoidance strategies by the pharmaceutical industry with vested interest in the process may also be responsible for at least some component of the popularity of steroid-free management both clinically and in the published literature. What is not known, however, is the actual long-term patient and graft outcomes and whether the theoretical benefits are actually realized or rather traded for different adverse issues (calcineurin nephrotoxicity, among others).
Findings.
This study used retrospective cohort data of all adult single-organ kidney transplants of any type using the Scientific Registry of Transplant Recipients (a US transplant registry) between 2000 and 2006. The two cohorts were grouped according to steroid-free or steroid-containing regimen at discharge and therefore did not differentiate from steroid avoidance and rapid steroid withdrawal. The authors noted wisely that this approach records medications at time of discharge only—observational with “as treated” analysis—but does not take into account any change or adjustments that occurred thereafter. Standard multivariate Cox regression models were used to assess primary end points of graft and patient survival. More than 90,000 patients were analyzed, representing a frequency of approximately 17.2% as steroid-free management at discharge (n = 16,491). In the final analysis, initial steroid-free management was statistically associated with better graft and mortality outcomes both short and long term (hazard ratio for graft failure and death at 1 yr 0.78 [95% confidence interval (CI) 0.72 to 0.85] and 0.73 [95% CI 0.65 to 0.82], respectively [P < 0.0001]; and at 4 yr 0.83 [95% CI 0.78 to 0.87] and 0.76 [95% CI 0.71 to 0.83], respectively [P < 0.0001]). An important table of baseline demographics informs the steroid-free group was slightly older (mean age 49.9), had fewer black patients, had more first transplants, had shorter time on dialysis, and had lower peak panel reactive antibody. Several of these factors were noted to have statistical significance but did not seem to have a major clinical difference.
Commentary.
The percentage of transplant centers that perform some type of steroid-free management strategy grew from 3.7% in 2000 to nearly one third (32.5%) in 2006. That means that this approach has gained sufficient traction that practice may have surpassed actual knowledge of outcomes. This article helps to highlight a number of important aspects that should be considered when counseling patients. Among these is the importance of initial selection of recipients at potentially low risk for immunologic events, the tradeoff for risks associated with calcineurin inhibitor–based therapy (including nephrotoxicity), and the likelihood of receiving potent induction therapy with agents that increase lifetime risk for malignancy and infection. Although reassuring in that steroid-free management at discharge was associated with lower risk for graft failure and death, this study is limited by its retrospective nature and selection bias. It does clearly speak to the need for well-structured prospective studies that will allow us to counsel our patients better on the risks and benefits of various immunosuppressive approaches.
Kidney transplant complications and obesity. Am J Surg 197: 424–426, 2009 Olarte IG, Hawasli A
Nephrologists, certainly in the United States, will agree that the number of overweight and obese patients who undergo both dialysis and renal transplantation has drastically increased in the past two decades. Studies on graft survival and complication rates of these obese patients have had conflicting results, with some reporting a significant risk and others reporting relatively good outcomes. One-year outcome data from our institution suggest no differences in outcomes with regard to surgical or wound complications, delayed graft function, or serum creatinine at 1 yr (1). Furthermore, length of stay, delayed graft function, and 1-yr graft survival were equivalent between obese and nonobese transplant recipients.
The actual effect of obesity per se on postoperative morbidity and mortality in the general population is well known; however, the increasing prevalence of this segment of the dialysis population can no longer be relegated to “nonaggressive” care, including blanket exclusion from the benefits of renal transplantation. Retrospective data on dialysis patients hints at a paradoxic benefit to survival in dialysis patients with increasing BMI (2), findings that are commonly attributed to improved nutrition. This study by Olarte and Hawasli is another in a series that help us to advise obese patients with regard to the relative risks and benefits of transplantation.
Findings.
This study intended to retrospectively examine renal allograft failure and other adverse outcomes in patients at a single Detroit hospital. Patients were classified as either obese when their body mass index (BMI) was ≥35 (n = 22) or nonobese when the BMI was <35 (n = 23). Obese patients who gained weight after transplantation had more postoperative complications (28 versus 18%), longer intraoperative time, and longer hospital length of stay compared with obese patients who did not gain weight after transplantation. Most interesting, the obese patients who did not gain weight postoperatively had a similar incidence of complications and similar creatinine to nonobese patients.
Commentary.
Most transplant centers have relaxed their “exclusion criteria” with regard to obesity, with new upper limit BMI values of approximately 35 replacing the old 31. This study highlights the importance of first-year postoperative weight gain (aka the “freshman 20”) as a detrimental factor with regard to functional outcome at 1 yr as reflected by the plasma creatinine (approximately 1.6 mg/dl in the weight gainers versus 1.0 mg/dl in the nongainers and nonobese). This suggests that early education and careful postprocedure attention to diet, nutrition, exercise, and weight control all influence outcome. The authors suggest consideration of gastrectomy and banding preoperatively. This approach, however, should be viewed with caution because effects on transit time as a result of dumping or potential for malnutrition can have catastrophic outcomes in this delicate population. Newer, reversible techniques, however, hold considerable promise and may be a solution when behavior modification fails to achieve weight management goals both before and after transplantation.
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