[Show abstract][Hide abstract] ABSTRACT: The choice of induction agent in the elderly kidney transplant recipient is unclear.
The risks of rejection at 1 year, functional graft loss, and death by induction agent (IL2 receptor antibodies [IL2RA], alemtuzumab, and rabbit antithymocyte globulin [rATG]) were compared among five groups of elderly (≥60 years) deceased-donor kidney transplant recipients on the basis of recipient risk and donor risk using United Network of Organ Sharing data from 2003 to 2008.
In high-risk recipients with high-risk donors there was a higher risk of rejection and functional graft loss with IL2RA versus rATG. Among low-risk recipients with low-risk donors there was no difference in outcomes between IL2RA and rATG. In the two groups in which donor or recipient was high risk, there was a higher risk of rejection but not functional graft loss with IL2RA. Among low-risk recipients with high-risk donors, there was a trend toward a higher risk of death with IL2RA.
rATG may be preferable in high-risk recipients with high-risk donors and possibly low-risk recipients with high-risk donors. In the remaining groups, although rATG is associated with a lower risk of acute rejection, long-term outcomes do not appear to differ. Prospective comparison of these agents in an elderly cohort is warranted to compare the efficacy and adverse consequences of these agents to refine the use of induction immunosuppressive therapy in the elderly population.
Clinical Journal of the American Society of Nephrology 05/2011; 6(5):1168-78. DOI:10.2215/CJN.07540810 · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine whether a higher body mass index (BMI) in kidney recipients is associated with delayed graft function (DGF), we analyzed data from 11,836 hemodialysis patients in the Scientific Registry of Transplant Recipients who underwent kidney transplantation. The patient cohort included women, blacks, and diabetics; the average age was 49 years; and the mean BMI was 26.8 kg/m(2). After adjusting for relevant covariates, multivariate logistic regression analyses found that one standard deviation increase in pretransplant BMI was associated with a higher risk of DGF (odds ratio (OR) 1.35). Compared with patients with a pretransplant BMI of 22-24.99 kg/m(2), overweight patients (BMI 25-29.99 kg/m(2)), mild obesity patients (BMI 30-34.99 kg/m(2)), and moderate-to-severe obesity patients (BMI 35 kg/m(2) and over) had a significantly higher risk of DGF, with ORs of 1.30, 1.42, and 2.18, respectively. Similar associations were found in all subgroups of patients. Hence, pretransplant overweight or obesity is associated with an incrementally higher risk of DGF.
Kidney International 04/2011; 80(2):218-24. DOI:10.1038/ki.2011.114 · 8.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait-listing, but data linking BMI changes to mortality during the waitlist period are lacking. By linking the 6-year (7/2001-6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time-dependent survival models examined the mortality predictability of 13-week-averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m². Each kg/m² increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95-0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66-0.86) and 0.57 (0.49-0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg- < 5 kg and ≥ 5 kg weight loss had death HRs of 1.31 (1.14-1.52) and 1.51 (1.30-1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant-waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear.
American Journal of Transplantation 04/2011; 11(4):725-36. DOI:10.1111/j.1600-6143.2011.03468.x · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetic patients with end-stage renal disease may receive a simultaneous pancreas-kidney (SPK) transplant. However, outcomes are not well described. Risks for death and graft failure were examined in SPK type 2 diabetic recipients.
Using the United Network for Organ Sharing database, outcomes of SPK transplants were compared between type 2 and type 1 diabetic recipients. All primary SPK adult recipients transplanted between 2000 and 2007 (n=6756) were stratified according to end-stage pancreas disease diagnosis (type 1: n=6141, type 2: n=582). Posttransplant complications and risks for death and kidney/pancreas graft failure were compared.
Of the 6756 SPK transplants, 8.6% were performed in recipients with a type 2 diabetes diagnosis. Rates of delayed kidney graft function and primary kidney nonfunction were higher in the type 2 diabetics. Five-year overall and death-censored kidney graft survival were inferior in type 2 diabetics. After adjustment for other risk factors, including recipient (age, race, body weight, dialysis time, and cardiovascular comorbidities), donor, and transplant immune characteristics, type 2 diabetes was not associated with increased risk for death or kidney or pancreas failure when compared with type 1 diabetic recipients.
After adjustment for other risk factors, SPK recipients with type 2 diabetes diagnosis were not at increased risk for death, kidney failure, or pancreas failure when compared with recipients with type 1 diabetes.
Clinical Journal of the American Society of Nephrology 03/2011; 6(5):1198-206. DOI:10.2215/CJN.06860810 · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association between pretransplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48 ± 13 years old and included 37% women and 27% diabetics. The higher pretransplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pretransplant serum albumin concentration was associated with 13% lower all-cause mortality (HR = 0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR = 0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR = 0.93[0.89-0.97]) and 4% lower DGF risk (OR = 0.96[0.93-0.99]). Hence, lower pretransplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-waitlisted hemodialysis patients and their impacts on post-transplant outcomes are indicated.
American Journal of Transplantation 03/2011; 11(5):1006-15. DOI:10.1111/j.1600-6143.2011.03480.x · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association between pretransplant body composition and posttransplant outcomes in renal transplant recipients is unclear. It was hypothesized that in hemodialysis patients higher muscle mass (represented by higher pretransplant serum creatinine level) and larger body size (represented by higher pretransplant body mass index [BMI]) are associated with better posttransplant outcomes.
Linking 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, 10,090 hemodialysis patients were identified who underwent kidney transplantation from July 2001 to June 2007. Cox regression hazard ratios and 95% confidence intervals of death and/or graft failure were estimated.
Patients were 49 ± 13 years old and included 49% women, 45% diabetics, and 27% African Americans. In Cox models adjusted for case-mix, nutrition-inflammation complex, and transplant-related covariates, the 3-month-averaged postdialysis weight-based pretransplant BMI of 20 to <22 and < 20 kg/m(2), compared with 22 to <25 kg/m(2), showed a nonsignificant trend toward higher combined posttransplant mortality or graft failure, and even weaker associations existed for BMI ≥ 25 kg/m(2). Compared with pretransplant 3-month- averaged serum creatinine of 8 to <10 mg/dl, there was 2.2-fold higher risk of combined death or graft failure with serum creatinine <4 mg/dl, whereas creatinine ≥14 mg/dl exhibited 22% better graft and patient survival.
Pretransplant obesity does not appear to be associated with poor posttransplant outcomes. Larger pretransplant muscle mass, reflected by higher pretransplant serum creatinine level, is associated with greater posttransplant graft and patient survival.
Clinical Journal of the American Society of Nephrology 03/2011; 6(6):1463-73. DOI:10.2215/CJN.09131010 · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study are to examine the incidence of new-onset diabetes mellitus after transplant (NODAT) and to identify its risk factors in adult lung transplant recipients using the Organ Procurement and Transplant Network/United Network of Organ Sharing database. Between July 2004 and December 2007, a total of 3540 adults (≥18 yr old) received their first single- or double-lung transplant alone and had at least one follow-up report of post-transplant diabetic status. Among these, 2991 recipients were identified as not having diabetes mellitus (DM) pre-transplant. Risk factors for NODAT were examined. DM was newly reported in 33.4% of the 2991 recipients over the median follow-up time of 670 d. Significant independent risk factors for the development of NODAT included male gender (HR = 1.15), recipient age ≥50 (1.46), African American (1.39), higher body mass index (1.51 for ≥30 vs. 18-25), cystic fibrosis (3.30), and tacrolimus use at discharge (1.67). NODAT occurred in a third of adult lung transplant recipients during the median follow-up period. Some of the risk factors for NODAT after lung transplant are similar to those reported in other solid-organ transplants. Cystic fibrosis is a strong risk factor for development of NODAT after lung transplant.
[Show abstract][Hide abstract] ABSTRACT: An increasing number of patients 80 years and older have received a kidney transplant in the United States, but their outcomes are not well described. Using Organ Procurement and Transplantation Network/United Network of Organ Sharing data, outcomes of recipients 80 years and older were evaluated.
Thirty-one thousand one hundred seventy-nine elderly recipients defined by age 60 years and older receiving kidney transplants from 2000 to 2008 were stratified: ages 60 to 69 years (n=24,877), 70 to 79 years (n=6,103), and 80 years and older (n=199). Cox regression models were used to compare patient, graft, and death-censored graft survival.
The majority of recipients 80 years and older was male (82.9%), white (87.9%), and less likely to have diabetes or coronary artery disease. More expanded criteria donor (ECD) but fewer living donor transplants were performed among 80 years and older compared with those younger than 80 years. Perioperative mortality, defined as death within 30 days posttransplant, was rare (60-69 years: 1.4%; 70-79 years: 1.5%; and ≥80 years: 2.5%) but tended to be higher among those 80 years and older compared with recipients 60 to 69 years (hazard ratio [HR] 1.67; 95% confidence interval [CI] 0.69-4.05). At 2 years, survival was lower for 80 years and older (73%; HR 2.42; 95% CI 1.91-3.06) and 70 to 79 years (86%; HR: 1.42; 95% CI: 1.34-1.51) compared with recipients 60 to 69 years (89%). There was a greater risk of graft loss among recipients 80 years and older compared with those 60 to 69 years (HR 1.78; 95% CI 1.42-2.23); however, no difference in death-censored graft survival was observed (0.89; 0.57-1.39). Among recipients 80 years and older, no difference in survival was observed between standard criteria donor and ECD recipients.
Although perioperative mortality was uncommon among elderly recipients (1.5%), a trend toward higher perioperative mortality was observed in recipients 80 years and older. There was no difference in survival among standard criteria donor and ECD recipients.
[Show abstract][Hide abstract] ABSTRACT: Living donor kidney transplantation (LDKT) in type 1 diabetic recipients (T1DM) may be followed by a pancreas after living donor kidney (PALK). The impact of the PALK is largely unknown. Adult T1DM living donor kidney recipients (1997-2007) listed for pancreas transplantation were divided into those who subsequently received pancreas transplantation and those who did not (living donor kidney transplant alone [LDKA]). Outcomes were compared. A sub-analysis was performed in recipients with at least one yr of kidney graft survival and limiting PALK to those who underwent pancreas transplantation in the first year. Of 4554 recipients, 23% received PALK. PALK had more favorable baseline characteristics. At the end of eight yr, we found significantly superior patient (85% vs. 75%) and kidney graft survival (75% vs. 62%) in PALK group. The adjusted hazard ratios of PALK (LDKA as reference) were 0.65 (95%CI: 0.52-0.81) for death and 0.63 (0.54-0.76) for renal graft loss. In sub-group analysis, there was a trend toward decreased death in PALK (HR = 0.78: 0.57-1.07). In conclusion, only 23% of those wait-listed received a pancreas with patient and kidney survival superior to LDKA. Pancreas transplant in the first year after kidney transplant was associated with a trend toward better long-term patient survival.
[Show abstract][Hide abstract] ABSTRACT: Our objectives are to examine the incidence of new-onset diabetes mellitus after transplant (NODAT) and to identify its risk factors in pediatric liver transplant recipients using the Organ Procurement and Transplant Network/United Network for Organ Sharing database. Between July 2004 and December 2008, a total of 1214 children (2-20 years old) received their first liver transplant alone, and had at least 1 follow-up report of posttransplant diabetic status. Among these, 1161 recipients were identified as not having diabetes mellitus before transplant. Risk factors for NODAT were examined using classification and regression tree and multivariate Cox regression analysis. Diabetes mellitus was newly reported in 10.1% of the 1161 recipients over the median follow-up time of 770 days. The cumulative incidences of NODAT at 1, 2, and 3 years after transplant were 5.9%, 8.3%, and 11.2%, respectively. More than 50% of recipients with cystic fibrosis developed NODAT. In recipients without cystic fibrosis, independent risk factors for NODAT included increased recipient age (compared to 2-5 years, hazard ratio = 3.09 for 5-13 years, p = 0.02; 7.14 for ≥13 years, p < 0.001), African American race (1.97, p = 0.003), and primary diagnosis of primary sclerosing cholangitis (2.24, p = 0.02) and acute hepatic necrosis (1.89, p = 0.04). In conclusion, NODAT occurred in one-tenth of pediatric liver transplant recipients in the United States during the median follow-up of 2 years. Some of the risk factors for NODAT in pediatric liver transplant recipients are similar to those reported in other solid organ transplants. Underlying liver disease of cystic fibrosis, primary sclerosing cholangitis, and acute hepatic necrosis are independent risk factors for NODAT in pediatric liver transplant recipients.
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular disease (CVD) is the leading cause of death in renal transplant recipients with a functioning allograft. Modification of CVD risk factors may, therefore, decrease overall mortality in this patient population. We studied renal transplant recipients within an integrated healthcare system (IHS) that uses case management and electronic health records to determine mortality from CVD.
We retrospectively collected data on all renal transplant recipients over a 10-year period. The primary endpoint was death with graft function (DWGF). Cardiovascular events were used as secondary endpoints. We determined the cause of death and collected laboratory data. The data were analyzed using Student's t test for continuous data, chi square for categorical data, and multivariate logistic regression. Survival was determined using the Kaplan-Meier product-limit method.
Death from "other" causes accounted for 29%. This was followed by CVD (24%), infection (16%), and malignancy (12%). The most common "other" causes were diabetes mellitus and end-stage renal disease. Overall, lower hemoglobin, uncontrolled blood pressure, and lower albumin levels were associated with DWGF. There were 184 cardiovascular events in total. Low-density lipid levels were lower in the group with cardiovascular events and DWGF. The use of antihypertensive and antihyperlipidemic agents was similar between the two groups with the exception of diuretics, which were used more often in the DWGF group.
There was a low rate of DWGF because of CVD within this IHS. It is possible that coordinated care within an IHS leads to improved cardiovascular mortality.
[Show abstract][Hide abstract] ABSTRACT: Diabetes and acute rejection are major contributors to morbidity and mortality in kidney transplant recipients. Immunosuppressive medications decrease acute rejection, but increase the frequency of new-onset diabetes after transplant. Our objective was to investigate the joint associations of diabetes (pretransplant diabetes and new-onset diabetes after transplant) and acute rejection with transplant outcomes in a recent transplant cohort.
Historical cohort study.
37,448 recipients (age ≥ 18 years; 2004-2007) surviving with a functioning transplant for longer than 1 year were identified in the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database as of May 22, 2009.
Recipients were stratified into 6 mutually exclusive groups according to status of diabetes and acute rejection at 1 year: group 1, neither (reference; n = 20,964); group 2, new-onset diabetes alone (n = 2,140); group 3, pretransplant diabetes alone (n = 10,730); group 4, acute rejection alone (n = 2,282); group 5, new-onset diabetes and acute rejection (n = 361); and group 6, pretransplant diabetes and acute rejection (n = 1,061). Analyses were adjusted for other recipient, donor, and transplant characteristics. OUTCOMES MEASUREMENTS: Multivariate Cox regression analysis of time to transplant failure (overall and death censored) and mortality (all-cause and cardiovascular).
Median follow-up after 1 year was 548 days (25th-75th percentiles, 334-752 days). During this time, there were 3,047 outcomes of overall transplant failure. New-onset diabetes alone (group 2) was not associated significantly with any study outcomes. Groups 3-6 were associated with higher overall transplant failure risk. However, only groups 4-6 were associated with higher death-censored transplant failure risk. Group 3, 4, and 6 were associated with higher all-cause mortality risk, whereas only groups 3 and 6 were associated with higher cardiovascular mortality risk.
Potential information bias with exposure, covariable, or outcome misclassification; relatively short follow-up.
Pretransplant diabetes is the major predictor of all-cause and cardiovascular mortality, and acute rejection during the first year is the major predictor of death-censored transplant failure in kidney recipients surviving with a functioning transplant for at least 1 year. The influence of new-onset diabetes on long-term outcomes needs further observation.
American Journal of Kidney Diseases 10/2010; 56(6):1127-39. DOI:10.1053/j.ajkd.2010.06.027 · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the effectiveness of induction therapy on transplant outcomes during 2004-2007 in the United States. We retrospectively reviewed OPTN/UNOS registry and selected kidney pediatric (<21-yr) recipients that received no induction (NoIND), IL-2RA, or rabbit anti-THY and were discharged with a triple drug immunosuppressive maintenance regimen, including steroids. Of 2932 recipients, 20%, 36%, and 43% were in NoIND, THY, and IL-2RA groups, respectively. The majority received tacrolimus (88%) and MMF (89%) at discharge. There was no association of induction with the risk of acute rejection even after adjusting for known cofounders. Compared to NoIND, IL2-RA, but not THY, had a modest decrease (3%) in absolute rate of graft loss and was associated with a risk reduction ratio of 0.51 (95% CI, 0.31-0.84) in one-yr graft loss. At three yr, no induction agent was associated with decreased graft loss. In conclusion, induction agents were used in 80% of pediatric kidney recipients discharged with a triple drug immunosuppressive maintenance regimen between 2004-2007 in the United States. Neither THY nor IL-2RA was associated with reduced rejection episodes. The use of induction therapy was not associated with improvement in three-yr graft survival.
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study are to investigate the impact of cytomegalovirus (CMV) donor (D)/recipient (R) serostatus on kidney transplant outcomes in recipients who received CMV prophylaxis and to investigate the association of individual antiviral agents (acyclovir, ganciclovir, and valganciclovir) with outcomes in high-risk recipients (D+/R-).
By using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, 25,058 deceased donor kidney recipients (≥ 18 years, 2004-2008) who received CMV prophylaxis were stratified into four groups: D+/R+ (11,875), D-/R+ (6046), D+/R- (4555), and D-/R- (2582). The impact of CMV D/R serostatus on acute rejection (6 months and 1 year posttransplant) and long-term outcomes of death-censored graft failure and mortality were compared. The impact of the individual antiviral agent on long-term outcome was further evaluated in the high-risk group (D+/R-).
In multivariate analysis, CMV D/R status was not associated with acute rejection. Compared with D-/R-, D+/R- was associated with an increased risk for death-censored graft failure (hazard ratio=1.28, P=0.01), all-cause mortality(hazard ratio=1.36, P=0.003), and mortality because of viral infection (hazard ratio=8.36, P=0.04). In the D+/R- group, valganciclovir usage was associated with a decreased risk for death-censored graft failure (hazard ratio=0.65, P=0.007) and mortality because of viral infection (hazard ratio=0.22, P=0.03) compared with ganciclovir usage.
CMV mismatch (D+/R-) was no longer a risk factor for acute rejection in kidney recipients who received antiviral prophylaxis but was still an independent risk factor for death-censored graft failure, all-cause mortality, and viral infection-related mortality.
[Show abstract][Hide abstract] ABSTRACT: The objectives of this study are to examine the incidence of new-onset diabetes mellitus (NODM) and to identify its risk factors in adult heart recipients using the Organ Procurement and Transplant Network/United Network of Organ Sharing database.
Between July 2004 and December 2007, 4972 adults (aged 18 years or older) received their first heart transplant alone, and had at least one follow-up report of posttransplant diabetic status. Among these, 3763 recipients were identified as not having diabetes mellitus pretransplant. Risk factors for NODM were examined using multivariate Cox regression analysis using the time to NODM diagnosis as a time-varying endpoint.
NODM was reported in 1075 (28.6%) of the 3763 recipients without pretransplant diabetes (median follow-up time, 713 days). Independent risk factors for development of NODM included older age (hazard ratio=1.20 for age >or=50 years vs. <50, P=0. 01), non-white race (0.70 for white vs. non-white, P<0.0001), higher body mass index (BMI) (1.55 for BMI >or=25 vs. <25, P<0.0001), ischemic heart disease (1.24, P<0.0001), recipient cytomegalovirus positivity (1.16, P=0.003), tobacco use (1.16, P=0.02), tacrolimus use at discharge (1.85 for tacrolimus vs. cyclosporine use, P<0.0001), and use of steroids at discharge (2.59 for steroid use vs. none, P=0.008).
NODM is common and occurs in more than a quarter of heart recipients during the median follow-up period of 2 years. Risk factors for NODM after heart transplant are similar to those reported in other solid organ transplants. Some of these factors, such as BMI and immunosuppressive regimen, are potentially modifiable.
[Show abstract][Hide abstract] ABSTRACT: Preexisting hepatitis C virus (HCV) infection is implicated in diminished patient and graft survivals in renal transplant recipients. The impact of HCV infection on patient and graft survival in simultaneous pancreas-kidney transplantations is unclear. We evaluated the effect of preexisting HCV infection on patient and graft survival in simultaneous pancreas-kidney transplant (SPKT) recipients in the United States.
Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database as of March 2009, adult primary SPKT recipients transplanted from 1995 to 2008 were studied. We stratified recipients based on pretransplant HCV status as HCV positive (HCV+) or HCV negative (HCV-). Overall kidney graft, pancreas graft, and patient survival were compared.
A total of 10,809 adults received primary SPKT, of which 350 (3.2%) were HCV+. Less than 2% of the HCV+ recipients received organs from HCV+ donors. There were no significant differences in baseline donor and recipient characteristics between groups. Rates of acute kidney rejection at 1 year were similar: 22.9% for HCV+ and 23.0% for HCV- recipients (P=0.49). There was no difference in serum creatinine between groups up to 3 years. After controlling for confounding factors, HCV positivity was not associated with worsened overall kidney graft (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.61-1.03), pancreas graft (HR 0.80, 95% CI 0.63-1.00), or patient survival (HR 0.78, 95% CI 0.56-1.08).
Only 3.2% of SPKT recipients had preexisting HCV infection. Preexisting HCV infection had no significant impact on kidney graft, pancreas graft, or patient survival.