Recipient Age and Time Spent Hospitalized in the Year Before and After Kidney Transplantation

Abstract

Background 

Kidney transplantation (KT) is a life-prolonging therapy in certain older end-stage renal disease patients, but concerns regarding peritransplantation morbidity remain. We estimate the relative increase in time spent hospitalized in the year post-KT for older versus younger end-stage renal disease patients.

Methods 

This was a retrospective analysis of 27,247 Medicare-primary KT recipients from 2000 to 2005 using United States Renal Data System and Organ Procurement and Transplantation Network data. Time spent hospitalized was enumerated in the year pre-KT and post-KT from Medicare Part A claims. Excess inpatient days were the difference in an individual’s post-KT and pre-KT hospital and skilled nursing facility days, standardized by time spent alive in the year post-KT.

Results 

The median excess inpatient days were similar by age group (9 in recipients 65 years or older vs. 7 in recipients younger than 65 years); however, the distribution was skewed, such that many more older adults had large increases in inpatient time (8.6% totaled >120 excess inpatient days vs. 4.2% in younger recipients). Among older recipients, risk factors for poor outcomes included recipient age, donor age, longer dialysis vintage, diabetic nephropathy, and congestive heart failure. Reasons for posttransplantation hospitalization were similar by age with the exception of rehabilitation, which was common only in the 65+ age group. Mean inpatient costs were equivalent pretransplantation by age but significantly higher posttransplantation among older KT recipients.

Conclusions 

Posttransplantation morbidity may not be so different in most of the older individuals selected for KT; however, a minority fares much worse.

Older adults are increasingly referred for kidney transplantation (^{1, 2}). In 2008, adults aged 65 years and older comprised 17% of the kidney transplant waiting list, up from 8% a decade earlier (¹). However, older adults make up nearly half of incident end-stage renal disease (ESRD) patients (¹), and access to transplantation remains exceedingly low (³). Although there is a clear survival advantage associated with kidney transplantation for the appropriately selected older transplant candidate compared with the remaining on dialysis (⁴), less is known about the tolerance of kidney transplantation in an older population or whether the impact of transplantation-related morbidity differs by recipient age.

Older ESRD patients may have distinct risk-benefit considerations for kidney transplantation. Older adults have smaller gains in expected life-years associated with transplantation compared with younger kidney transplant recipients (⁵), and their perioperative morbidity may be higher. For example, older adults may experience higher infection rates after standard immunosuppression protocols given age-related changes in immune response (⁶). Steroid therapy may predispose already frail older transplant candidates to increased rates of fracture (⁷). Finally, older adults generally shoulder a higher burden of comorbid conditions, and they may face longer posttransplantation recovery times and higher surgical complication rates (⁸). These hypothetical increases in transplant-related morbidity among older transplant recipients may result in decreased quality of life—an important consideration in patients with relatively short expected survival (⁹).

Hospitalizations are an important and underutilized proxy for comparing posttransplantation morbidity across age groups. Careful interpretation is required: greater time spent hospitalized posttransplantation may be attributable to poorer tolerance of the transplantation itself, but it may also be attributable to preexisting medical conditions. Older patients might be expected to spend more time in the hospital than a younger patient regardless of whether they received a transplant. Using a novel method to adjust for this baseline nontransplantation morbidity, the aim of this study was to compare posttransplantation hospitalization patterns between older and younger recipients, benchmarking to an individual’s pretransplantation hospitalization pattern.

RESULTS

Baseline and Transplant Characteristics

From 2000 to 2005, there were 4807 Medicare-primary transplant recipients aged 65 years and older and 22,440 between the ages of 18 and 64 years (Table 1). There were smaller proportions of female and black recipients among older age groups. Except for drug abuse and current smoking, the older recipients had a greater burden of comorbid conditions than their younger counterparts (mean number of comorbidities, 2.1 vs. 1.7; P<0.001). The older adults had a slightly shorter pretransplantation time on dialysis (3.3 vs. 3.9 years, P<0.001), and they more often received expanded-criteria donor organs (27.1% vs. 15.8%, P<0.001). The rate of live-donor transplantation was lower for the older versus younger recipients overall (18.3% vs. 20.6%, P<0.001), although this was driven mostly by the high live-donor rates in 18- to 39-year-olds.

TABLE 1: Study population characteristics, by recipient age

Peritransplantation Hospitalization

In the year pretransplantation, the older recipients spent, on average, slightly less time hospitalized than younger recipients (mean, 5.4 vs. 5.8 days; P=0.03) but slightly more time in skilled nursing facilities (mean, 0.5 vs. 0.3 days; P=0.004). There was no difference in the median pretransplantation days spent hospitalized or in skilled nursing facilities by age group (2 days and 0 day, respectively), reflecting a skew in the distribution (Table 2). On average, the older recipients spent significantly more days in the hospital for the transplantation itself (mean, 7.9 vs. 6.9 days; P<0.001) and more time in skilled nursing facilities in the year posttransplantation (mean, 3.7 vs. 1.2 days; P<0.001); again, medians were similar by age category, with the exception of days spent hospitalized for reasons other than the transplantation (Table 2).

TABLE 2: Pretransplantation and posttransplantation hospitalization and skilled nursing facility time, by age at transplantation

When benchmarked to an individual recipient’s hospitalization pattern in the year pretransplantation, differences in inpatient time (“excess inpatient days”) between the older and younger age groups were more pronounced (Table 2). Whereas the median excess inpatient days remained similar (5, 6, 7, and 9 days in the 18–39, 40–49, 50–64, and 65+ age groups, respectively), the interquartile range of excess inpatient days increased with age (2–12, 2–16, 2–19, and 3–24, respectively); this increase in interquartile range was greater still when excess inpatient days were standardized to the time spent alive in the year posttransplantation (Table 2). Similarly, the distribution of standardized excess inpatient days was markedly different by age group (Fig. 1A). The older adults were more likely to spend more than 120 standardized excess inpatient days posttransplantation than any other age group (1.4%, 2.7%, 5.4%, and 8.6% of the 18–39, 40–49, 50–64, and 65+ age groups, respectively).

FIGURE 1: By age group: distribution of standardized excess inpatient days (A) and mean costs (B). Standardized excess inpatient days = inpatient days in the year posttransplantation (standardized to 1-year survival) − inpatient days in the year pretransplantation.

Stratification by Donor Type

Among live-donor recipients, the disparities in outcomes by age group were attenuated. The proportions of recipients with more than 120 standardized excess inpatient days were 1.1%, 1.7%, 3.5%, and 5.1% in the 18 to 39, 40 to 49, 50 to 64, and 65+ age groups, respectively. The 1-year mortality rates were also lower among live-donor recipients, at 1.8%, 3.0%, 5.1%, and 6.6% by increasing age group. The median standardized excess inpatient days were similar (4, 4, 4, and 5 days among recipients aged 18–39, 40–49, 50–64, and 65+ years, respectively), as were the corresponding distributions (interquartile range of standardized excess inpatient days, 1–10, 0–12, 1–13, and 1–16 by increasing age group). Compared with deceased-donor recipients, live-donor recipients spent more time hospitalized in the year pretransplantation (mean, 6.8 days among live donors vs. 5.4 days among deceased donors, P<0.001; median, 2 days for both groups); this was true within each age group. Conversely, live-donor recipients spent less time hospitalized in the year posttransplantation than their deceased-donor counterparts (inpatient days among all ages: mean, 15.0; median, 8; interquartile range, 4–17 among live-donor recipients; and mean, 19.6; median, 11; interquartile range, 6–23 among deceased-donor recipients).

Poor Outcome Among Older Adults

Recipient characteristics significantly associated with poor outcome (>120 excess inpatient days or death in the year posttransplantation) among recipients aged 65 years and older included age (adjusted odds ratio [aOR], 1.42 per decade; 95% confidence interval [CI], 1.11–1.81; P=0.005), time on dialysis pretransplantation (aOR, 1.11 per year; 95% CI, 1.05–1.17; P<0.001), time spent hospitalized in the year pretransplantation (aOR, 1.08 per week; 95% CI, 1.02–1.16; P=0.01), diabetes (aOR, 1.49; 95% CI, 1.11–2.01; P=0.008) or hypertension (aOR, 1.46; 95% CI, 1.07–1.99; P=0.02) as the primary cause of renal disease, and the presence of congestive heart failure (aOR, 1.27; 95% CI, 1.02–1.58; P=0.03) (Table 3). Transplant characteristics associated with poor outcome included donor age (aOR 1.11 per decade, 95% CI: 1.03–1.19, P=0.005); live donor (aOR 0.59, 0.44–0.79, P<0.001) and later transplant year (aOR 0.93 per year, 95% CI: 0.88–0.98, P=0.007) were protective. Expanded-criteria donor organs had no independent association with outcome (aOR, 1.11; 95% CI, 0.85–1.45; P=0.4), likely because of the collinearity between donor age and expanded-criteria donor status. When the entire transplant recipient population was included, there was a statistically significant interaction between age category and diabetes as a cause of renal failure, with diabetes conferring higher odds of poor outcomes among younger age groups (ages 18–39 years: aOR, 2.55; 95% CI, 1.75–3.79; P<0.001; ages 40–49 years: aOR, 2.01; 95% CI, 1.50–2.70; P<0.001; ages 50–64 years: aOR, 1.83; 95% CI, 1.50–2.22; P<0.001; ages 65+ years: aOR, 1.39; 95% CI, 1.12–1.72; P=0.003).

TABLE 3: Factors associated with poor outcomes (≥33% of the year post-KT spent hospitalized or death) among older transplant recipients, multivariable model

Causes of Hospitalization Posttransplantation

The top 5 reasons for hospitalization in the year posttransplantation (excluding the hospitalization for the transplantation itself) were fairly similar across age groups (Table 4). The 2 most common causes of hospitalization were genitourinary system symptoms or procedures (including kidney, ureter, bladder procedures, prostatectomy, kidney stones, and other kidney and urinary tract signs and symptoms) and infection (most commonly infectious disease, septicemia, urinary tract infection, and pneumonia). Circulatory disorders were the third most common reason for hospitalization in recipients aged 40 years and older. Despite the higher prevalence of diabetes in older adults, endocrine hospitalizations were not among the top 5 reasons for hospitalizations in older adults, although they were in the younger transplant recipient population. Rehabilitation was among the top 5 reasons for hospitalization only in older recipients.

TABLE 4: Top 5 reasons for hospitalization posttransplantation, by age

Costs Before and After Transplantation

Overall, Medicare costs were similar in the year pretransplantation when stratified by age group, and these costs increased slightly over time (P<0.001, Fig. 1B). There was no difference in costs in the year posttransplantation between recipients aged 50 to 64 and 65+ years (P=0.3); however, they were both significantly larger than posttransplantation costs in the 18 to 39 and 40 to 49 age groups. Posttransplantation costs increased significantly over time in both the 18 to 39 and 65+ age groups (P<0.001).

DISCUSSION

This national study of hospitalization patterns before and after kidney transplantation further supports the growing body of evidence that appropriately selected older adults can and do thrive after kidney transplantation (^{10, 11}). Compared with younger transplant recipients, older transplant recipients had similar median, yet higher mean, inpatient days in the year after transplantation, both before and after adjustment for baseline hospitalization patterns and mortality. Posttransplantation hospitalization burden for most of the older adults was relatively comparable with that for their younger counterparts; a minority of older recipients, however, fared much worse. Better tools to risk-stratify older kidney transplant candidates are needed.

Renal replacement therapy, even dialysis initiation, among older adults remains somewhat controversial. Therapeutic nihilism is common and not without evidence: studies from the United Kingdom indicate that older ESRD patients choosing conservative (nondialysis) therapy may have equivalent survival to matched controls initiating dialysis (^{12, 13}). Deceased-donor kidney transplantation in older adults places a limited resource in a population with a reduced life expectancy (^{2, 14}). Although older kidney transplant recipients report higher quality of life than their counterparts on dialysis (¹⁵), the expected gains in quality of life after transplantation may be offset by a complicated posttransplantation course (¹⁶). Factors associated with poor transplantation outcomes, such as malnutrition, depression, and poor functional status, are disproportionately prevalent in the older ESRD population (^17–19). Our study suggests that most older adults’ pretransplantation and posttransplantation hospitalizations, both important predictors of quality of life among older adults (¹⁶), are similar to those experienced in younger transplant recipients. However, poor outcomes after transplantation may be magnified in the older population: the upper range of posttransplantation inpatient days and short-term mortality was much higher.

A notable finding of our study was the relative success of living-donor transplantation among older persons. One-year survival among older living-donor transplant recipients was high at 93.3%, and the posttransplantation hospitalization experience was minimally different from younger living-donor transplant recipients. A priori, we thought providers might be uneasy listing an older adult “to the detriment” of a potential younger candidate, given the length of the deceased-donor waiting list. If this were true, providers might be more willing to refer marginal candidates with a potential live donor. We did observe that live-donor recipients spent more time hospitalized in the year pretransplantation than deceased-donor recipients, suggesting that this differential consideration may play a role in transplant candidate selection. However, even if older living-donor recipients were in poorer health at the time of transplantation than their age-matched deceased-donor counterparts, they appeared to tolerate live-donor transplantation similar to younger age groups.

Existing literature on transplantation-associated morbidity among older adults is limited. In a single-center study of 271 patents, adults older than 60 years had posttransplantation experiences similar to those of younger transplant recipients in perioperative morbidity, length of stay, and hospital readmissions (²⁰). In another single-center study of 527 living-donor transplant recipients, older adults had significantly higher rates of readmission but not length of stay (²¹). However, these studies are small, lack the power to detect some clinically meaningful differences, and potentially lack generalizability. The observation in our large national study that kidney transplant lengths of stay are slightly higher for older adults is consistent with trends seen in the general U.S. population, where all-cause hospital rates and lengths of stay are increased among adults older than 65 years (²²).

The strengths of this study include the large sample size, the novel method for determining (and standardizing) posttransplantation hospitalizations, and the likely generalizability to the overall kidney transplant candidate population. Our study population captures much of the U.S. kidney transplant recipient pool and is over 50 times larger than of previous studies. We use excess hospital days as a novel measure of hospitalizations posttransplantation with an “internal control” for expected (i.e., pretransplantation) hospitalizations. Hospitalization records were extracted from administrative data, likely yielding a more accurate quantification of hospital days than that possible from a single transplant center source, where outside hospitalizations may be missed.

However, several important limitations merit consideration. Claims data may have a low sensitivity in identifying hospitalization complications (^{23, 24}). We limited our population to Medicare-primary patients, a criterion that could differentially affect older and younger patients. Given that all ESRD patients requiring dialysis therapy are eligible for Medicare, this is a common inclusion criterion in studies of ESRD patients (^{17, 25, 26}), and one in which we believe should only minimally bias the results. Also, there may be a differential threshold for hospitalization admissions among younger and older transplant recipients. If so, however, we would expect older adults to be more readily hospitalized, and inferences from the existing study would be conservative.

In conclusion, this study provides national data regarding the hospitalization experience in the year before and after kidney transplantation in younger and older recipients. Time spent hospitalized in the year posttransplantation and excess inpatient days are novel measures, which may serve as important proxies for inferior quality of life and severe posttransplantation morbidity. We demonstrate that, despite a substantially increased burden of comorbid conditions and inferior graft characteristics, most older transplant recipients have similar posttransplantation hospitalization patterns to their younger counterparts, although a minority of older transplant recipients fared very poorly. On the basis of these findings, we support continued efforts to improve access to transplantation for older ESRD patients. However, older candidates should be counseled about their higher risk of severe morbidity and death in the year after kidney transplantation, and efforts should be intensified to improve the prediction of poor transplantation outcomes within the older transplant candidate population. Better identification of transplant recipients at risk for prolonged hospital stays could spur development of surveillance protocols to improve posttransplantation outcomes and reduce rehospitalization rates.

MATERIALS AND METHODS

The study population was composed of 27,247 adult first-time kidney-only transplant recipients between January 1, 2000 and December 31, 2005, as reported to the Organ Procurement and Transplantation Network. The population was limited to those recipients with Medicare as their primary insurer continuously for the 2-year peritransplantation period (encompassing 365 days pre–kidney transplantation and post–kidney transplantation). Donor, recipient, and transplant characteristics were gleaned from the United States Renal Data System, Organ Procurement and Transplantation Network transplant candidate and recipient registration forms, and the Centers for Medicare & Medicaid Services claims. Mortality information was augmented with the Social Security Death Master File.

The outcome of interest was number of days spent hospitalized in the year after transplantation (including the hospitalization for the transplantation itself), estimated from Medicare Part A claims. Excess inpatient days were calculated as the number of inpatient days (either in a skilled nursing facility or in a hospital) over the year posttransplantation minus the number of inpatient days over the year pretransplantation. To account for the higher rates of death in the older age groups (and thus fewer days at risk for hospitalization), a standardized measure of excess inpatient days was constructed by scaling posttransplantation inpatient days by the time spent alive in the year posttransplantation. Hospitalizations were classified by International Classification of Diseases, 9th Revision, Clinical Modification codes into 35 broad categories. Inpatient Medicare costs were also analyzed as a secondary outcome.

Comparisons of baseline variables between younger and older transplant recipients were performed using chi-square and t tests as appropriate. Logistic regression was used to study factors associated with a poor outcome, namely, 120 days or more excess inpatient days or death within a year posttransplantation; factors evaluated included patient sex, ethnicity, years on dialysis pretransplantation, cause of ESRD, body mass index (BMI), Form 2728 comorbidities, donor age, donor type (living or deceased, expanded-criteria donor), and hospital days in the year pretransplantation. To determine whether the effect of diabetic nephropathy on poor outcomes differed by age, an interaction term between the 2 variables was also tested. All statistical analyses were performed using Stata 11.0/MP (StataCorp, College Station, TX).

ACKNOWLEDGMENTS

The authors thank the staff of the Organ Procurement and Transplantation Network and the United States Renal Disease System for provision of the data. The Organ Procurement and Transplantation Network is supported by Health Resources and Services Administration contract 234-2005-370011C. The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.