[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.
[show abstract][hide abstract] ABSTRACT: One of the alternative options to simultaneous pancreas-kidney transplantation (SPKT) for type I diabetics with renal failure is sequential transplant of a living donor kidney followed by a deceased donor pancreas transplant (pancreas after living donor kidney transplant [PALK]). We retrospectively compared the outcomes of SPKT versus PALK.
Adults (age 18-59 years) with type I diabetes who were waitlisted for kidney-pancreas and received a SPKT or PALK between 2000 and 2007 were studied. We compared patient, kidney graft, and pancreas graft survival. Multivariate analysis was performed, and the results were expressed as hazard ratios (HRs) of graft loss and death of PALK, with SPKT as a reference.
Of 11,966 patients who received a kidney transplant, 807 received a PALK and 5580 received a SPKT. Median time to pancreas from kidney transplant was 336 (25%-75%: 185-602 days) days. Average hospital stay for SPKT recipients was 13.2+/-15 days, whereas for PALK recipients was 5.7+/-4 days and 9.5+/-8 days for kidney and pancreas transplants, respectively. After controlling for confounding factors, patients receiving PALK had better patient survival (HR 0.52; 95% confidence interval [CI] 0.39-0.70) and kidney survival (HR 0.48; 95% CI 0.39-0.60) but worse pancreas survival (HR 1.37; 95% CI 1.16-1.62) compared with SPKT.
Among those who were waitlisted for a kidney-pancreas transplant, 53% received a kidney-pancreas transplant. Of those who received a kidney-pancreas transplant, 87% patients underwent SPKT and 13% underwent PALK. PALK was associated with better kidney graft and patient survival compared with SPKT. We found an inferior pancreas graft survival and longer total transplant hospitalization in PALK.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE.: To analyze the risk factors for new-onset diabetes mellitus (NODM) in liver transplant recipients using the Organ Procurement and Transplant Network/United Network for Organ Sharing database. METHODS.: Among 20,172 primary liver recipients (age > or =18 years) transplanted between July 2004 and December 2008 in Organ Procurement and Transplant Network/United Network for Organ Sharing databases, 15,463 recipients without pretransplant diabetes were identified. Risk factors for NODM were examined using multivariate Cox regression analysis. RESULTS.: NODM was reported in 26.4% of recipients (median follow-up, 685 days). Independent predictors of NODM development included recipient age (> or = 50 vs. <50 years, hazard ratio [HR]=1.241), African American race (HR=1.147), body mass index (> or = 25 vs. <25, HR=1.186), hepatitis C (HR=1.155), recipient cirrhosis history (HR=1.107), donor age (> or = 60 vs. <60 year, HR=1.152), diabetic donor (HR=1.151), tacrolimus (tacrolimus vs. cyclosporine, HR=1.236), and steroid at discharge (HR=1.594). Living donor transplant (HR=0.628) and induction therapy (HR=0.816) were associated with a decreased risk of NODM. CONCLUSION.: The incidence of NODM was 26.4% in liver recipients with a median follow-up time of 685 days. Identified risk factors for NODM in liver transplantation were similar to that in kidney transplantation. Some of the identified factors are potentially modifiable, including obesity and the choice of immunosuppressive regimens.
[show abstract][hide abstract] ABSTRACT: BACKGROUND.: In kidney transplant, obesity was reported to be associated with increased posttransplant complications and worse survival outcomes. The impact of obesity in simultaneous pancreas-kidney (SPK) transplant is less known. METHODS.: Using Organ Procurement Transplantation Network/United Network for Organ Sharing data as of August 2008, we included all adults (>18 years) type 1 diabetic SPK recipients between years 2000 and 2007 with a pretransplant body mass index (BMI) of 18.5 to 40 kg/m. The cohort was divided in three groups: normal (BMI 18.5-24.9 kg/m, reference group), overweight (BMI 25-29.9 kg/m), and obese (BMI 30-40 kg/m). Covariate-adjusted relative risk of a combination of posttransplant complications and patient, pancreas and kidney allograft outcomes were evaluated. RESULTS.: Of 5725 recipients, 56%, 33%, and 11% were in normal, overweight, and obese groups, respectively. Overweight and obese recipients were older, had a higher percent of coronary artery disease, and private health insurance coverage. Overall posttransplant complications were higher in obese group (35.7% vs. 28.6%) when compared with normal BMI group. They were mainly due to increased delayed kidney graft function (11.8% vs. 7.4%), 1-year kidney acute rejection (17.0% vs. 12.1%), and pancreas graft thrombosis (2.6% vs. 1.3%). After adjusting for possible confounders, the odds ratios for overall transplant complications were 1.03 (95% confidence interval [CI]: 0.90-1.17) for overweight and 1.38 (95% CI: 1.15-1.68) for obese. Obesity, but not overweight, was associated with patient death (hazard ratio [HR]: 1.35; 95% CI: 1.00-1.81), pancreas graft loss (HR: 1.41; 95% CI: 1.17-1.69), and kidney graft loss (HR: 1.33; 95% CI: 1.05-1.67) at 3 years. The higher rates of death and graft failure in the first 30 days posttransplant mostly accounted for the 3-year survival differences. CONCLUSION.: Obesity in SPK recipients was associated with increased risk of posttransplant complications, pancreas and kidney graft loss, and patient death.
[show abstract][hide abstract] ABSTRACT: The objective of this study was to identify the risk factors for new-onset diabetes mellitus (NODM) after kidney transplant in pediatric renal transplant recipients using Organ Procurement Transplant Network/United Network of Organ Sharing database.
A total of 2726 nondiabetic primary kidney transplant recipients (age 2-20 years, transplanted between July 2004 and December 2007) in the Organ Procurement Transplant Network/United Network of Organ Sharing database as of August 2008 with at least one follow-up report were included. We examined the risk factors for NODM using multivariate Cox regression analysis using the time to NODM reported as a time-varying endpoint. In recipients with functional graft at 1 year after transplant, the graft survivals during subsequent 24 months were compared according to the presence of NODM within first year of transplant.
NODM was reported in 4.6% (median follow-up time: 693 days). Independent risk factors for NODM included increased age (>10 years vs. <10 years, hazard ratio [HR]=2.143, P=0.015), abnormal body mass index percentile (<5% or >85% vs. 5%-85%, HR=1.697, P=0.01), and steroid use at discharge (yes vs. no, HR=3.573, P=0.03). Living donor transplant was associated with a decreased risk of NODM (living vs. deceased, HR=0.629, P=0.05). NODM within first year of transplant was not associated with inferior graft survival during subsequent 24 months.
Some of the identified risk factors for NODM are potentially modifiable, including abnormal body mass index percentile and the use of steroid. Prospective clinical trials are needed to assess whether modifying these risk factors will prevent NODM.
[show abstract][hide abstract] ABSTRACT: Alemtuzumab use has been increasing in kidney transplantation. We aimed to compare posttransplantation outcomes between alemtuzumab and interleukin-2 receptor antibodies (IL-2RA) in living donor kidney transplant recipients in the United States.
Organ Procurement Transplant Network/United Network of Organ Sharing data, as of August 2007, were used to identify all living donor kidney transplants performed in adults in the United States from 2003 to 2006 where induction therapy with alemtuzumab or IL-2RA (daclizumab or basiliximab) was used. Primary outcomes included incidence of acute rejection, graft survival, and patient survival.
One thousand nine hundred thirteen recipients received alemtuzumab and 7011 received IL-2RA. There were few significant differences in baseline characteristics. The incidence of acute rejection at discharge was lower in the alemtuzumab group, when compared with that in the IL-2RA group (0.8% vs. 4.4%, respectively, P<0.001), but it was similar by 1 year posttransplant (9.8% vs. 11%, respectively). After adjusting for confounding factors, those in alemtuzumab group had a higher adjusted relative risk of graft loss (hazard ratios 1.23, 95% CI 1.03-1.48) in 4 years. Patient survival was comparable between the study groups. A higher rate of acute rejection and graft failure was seen in the recipients who used triple regimen (calcineurin-mycophenolate-steroid) in association with alemtuzumab.
The incidence of acute rejection at discharge was lower with alemtuzumab but was comparable with IL-2RA up to 1 year posttransplant. There was no difference in patient survival, but the risk of graft loss among patients who received alemtuzumab was higher compared with those who received IL-2RA induction.
[show abstract][hide abstract] ABSTRACT: Risk of new-onset diabetes after transplant (NODAT) is well characterized for adults but much less understood in pediatric transplant. This study examines the incidence and risk factors of NODAT in pediatric renal transplant patients.
The incidence of NODAT over the first 3 years after transplant was examined with the United States Renal Data System data for primary renal transplant recipients (ages 0-21 years, transplanted between 1995 and 2004) with Medicare primary. Patients had no evidence of diabetes before transplant. We estimated the cumulative incidence rate and used Cox proportional hazards regression to identify the risk factors for NODAT. Propensity scores were calculated for immunosuppression choice to adjust for potential confounding factors.
Two thousand one hundred sixty-eight recipients with valid immunosuppression records and without pretransplant evidence of diabetes were included. Unadjusted, cumulative NODAT incidence at 3 years posttransplant was 7.1%. Significant factors for increased risk of NODAT included cytomegalovirus D+/R- serostatus (adjusted hazard ratio [aHR]=1.60), age 13 to 18 years (aHR=2.18), age 19 to 21 years (aHR=2.60), body mass index more than or equal to 30 kg/m (aHR=2.17), and use of tacrolimus (aHR=1.51). We failed to find any significant relationships between NODAT and graft failure or death.
Although the incidence of NODAT among patients aged 0 to 21 years is lower than that for adult patients, it is higher than suggested by earlier research and may represent an increase over time. The lack of association between NODAT and graft or failure death has important implications for posttransplant care. A clearer understanding of risk factors can help guide posttransplant monitoring and clinical decision making.
[show abstract][hide abstract] ABSTRACT: In participants of the CONVERT trial, which enrolled recipients of kidney transplants, conversion of immunosuppressive therapy from calcineurin inhibitors to sirolimus did not improve renal function. More importantly, the intervention was detrimental among patients with impaired kidney function and/or proteinuria. Sirolimus conversion resulted, however, in lower rates of malignancy.
[show abstract][hide abstract] ABSTRACT: Simultaneous heart-kidney transplantation (SHK) remains uncommon in the US. We examined outcomes of SHK compared to heart transplant alone (HTA) and deceased donor kidney transplant (DDKT). Data from OPTN/UNOS heart and kidney data bases were used to identify 16,710 HTA, 263 SHK transplants and 68,833 DDK transplants between 1998 and 2007. Outcomes included patient survival (PS), acute cardiac and renal rejection and renal graft survival (rGS). The adjusted risk of death was 44% lower with SHK compared to HTA. Over half of SHK were performed in cases where pretransplant dialysis was not initiated. In these cases, there was no significant difference in the risk of death between SHK and HTA (HR 1.01; 95% CI 0.67-1.50). Recipients of SHK had worse 1-year rGS and PS and had a higher relative risk of overall renal graft loss compared to DDKT recipients. One-year rates of cardiac (14.5%) and renal (6.5%) rejection were lower in SHK compared to HTA and DDKT, respectively. Recipients of SHK had a lower adjusted risk of death compared to HTA recipients, particularly in patients who required pretransplant dialysis. These data suggest that SHK should be considered in heart transplant candidates with renal failure requiring dialysis, whereas the utility of SHK in cases of renal failure not requiring dialysis warrants further study.
American Journal of Transplantation 05/2009; 9(4):844-52. · 6.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transplant options for type I diabetics with end-stage renal disease include simultaneous pancreas-kidney (SPKT), living donor kidney (LDKT), and deceased donor kidney transplant (DDKT). It is unclear whether SPKT offers a survival benefit over LDKT in the current era of transplantation. The authors compared outcomes of kidney transplant recipients with type I diabetes using data from the Organ Procurement and Transplant Network/United Network for Organ Sharing.
Adult (age 20 to 59) type I diabetics who received a solitary first-time kidney transplant between 2000 and 2007 were studied. Outcomes included overall kidney graft and patient survival. Multivariate analysis was performed using a stepwise Cox proportional hazards model.
Kidney graft survival was better for recipients of LDKT compared with SPKT (P = 0.008), although patient survival was similar (P = 0.346). On multivariate analysis, LDKT was associated with lower adjusted risks over 72 mo follow-up of kidney graft failure (HR 0.71; 95% CI 0.61 to 0.83) and patient death (HR 0.78; 95% CI 0.65 to 0.94) versus SPKT. Compared with DDKT, SPKT had superior unadjusted kidney graft and patient survival, partly due to favorable SPKT donor and recipient factors.
Despite more transplants from older donors and among older recipients, LDKT was associated with superior outcomes compared with SPKT and was coupled with the least wait time and dialysis exposure. LDKT utilization should be considered in all type I diabetics with an available living donor, particularly given the challenges of ongoing organ shortage.
Clinical Journal of the American Society of Nephrology 02/2009; 4(4):845-52. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Fabry disease is a rare but important cause of end-stage renal disease (ESRD) among young men. Postkidney transplantation outcomes among patients with Fabry disease remain controversial.
Using data from Organ Procurement Transplant Network/United Network for Organ Sharing, 197 kidney transplant recipients with ESRD because of Fabry disease from 1987 to 2007 were identified. We compared rates of graft loss and death with those of kidney transplant recipients with other (non-Fabry) causes of ESRD. Fabry patients were then compared with a 10:1 matched cohort of transplant recipients with other causes of ESRD.
Five-year graft survival was superior among Fabry patients (74%) compared with those with other causes of ESRD (69%), but was similar to those in the matched cohort (P=0.64). Five-year patient survival among Fabry patients (81%) was similar to those with other causes of ESRD (P=0.33), but was inferior to the matched cohort (90%). Cox multivariate analysis revealed that Fabry patients had a 40% lower risk of returning to dialysis compared with both matched and unmatched cohorts, but had a higher risk of death (2.15; 1.52-3.02) compared with the matched cohort.
This analysis of 197 kidney transplant recipients with Fabry indicates that they have superior graft survival and similar patient survival compared with patients with other causes of ESRD. However, Fabry patients had a higher risk of death compared with a matched cohort of patients with other causes of ESRD. This requires further investigation and may suggest a need for further attention to the minimization of cardiovascular death in this group of patients.
[show abstract][hide abstract] ABSTRACT: Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival.
We examined 2-year (July 2001 to June 2003) mortality in 34,107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to > or =4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain <1.0 kg and > or =4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively.
In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.
[show abstract][hide abstract] ABSTRACT: Whether to include additional comorbidities beyond diabetes in future kidney allocation schemes is controversial. We investigated the predictive ability of multiple pretransplant comorbidities for graft and patient survival. We included first-kidney transplant deceased donor recipients if Medicare was the primary payer for at least one year pretransplant. We extracted pretransplant comorbidities from Medicare claims with the Clinical Classifications Software (CCS), Charlson and Elixhauser comorbidities and used Cox regressions for graft loss, death with function (DWF) and death. Four models were compared: (1) Organ Procurement Transplant Network (OPTN) recipient and donor factors, (2) OPTN + CCS, (3) OPTN + Charlson and (4) OPTN + Elixhauser. Patients were censored at 9 years or loss to follow-up. Predictive performance was evaluated with the c-statistic. We examined 25 270 transplants between 1995 and 2002. For graft loss, the predictive value of all models was statistically and practically similar (Model 1: 0.61 [0.60 0.62], Model 2: 0.63 [0.62 0.64], Models 3 and 4: 0.62 [0.61 0.63]). For DWF and death, performance improved to 0.70 and was slightly better with the CCS. Pretransplant comorbidities derived from administrative claims did not identify factors not collected on OPTN that had a significant impact on graft outcome predictions. This has important implications for the revisions to the kidney allocation scheme.
American Journal of Transplantation 01/2009; 9(3):494-505. · 6.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transplant "tourism" typically refers to the practice of traveling outside the country of residence to obtain organ transplantation. This study describes the characteristics and outcomes of 33 kidney transplant recipients who traveled abroad for transplant and returned to University of California, Los Angeles (UCLA) for follow-up. Design, settings, participants, & measurements: Posttransplantation outcomes were compared between tourists and a matched cohort of patients who underwent transplantation at UCLA (matched for age, race, transplant year, dialysis time, previous transplantation, and donor type). Median follow-up time was 487 d (range 68 to 3056).
Compared with all patients who underwent transplantation at UCLA, tourists included more Asians and had shorter dialysis times. Most patients traveled to their region of ethnicity with the majority undergoing transplantation in China (44%), Iran (16%), and the Philippines (13%). Living unrelated transplants were most common. Tourists presented to UCLA a median of 35 d after transplantation. Four patients required urgent hospitalization, three of whom lost their grafts. Seventeen (52%) patients had infections, with nine requiring hospitalization. One patient lost her graft and subsequently died from complications related to donor-contracted hepatitis B. One-year graft survival was 89% for tourists and 98% for the matched UCLA cohort (P = 0.75). The rate of acute rejection at 1 yr was 30% in tourists and 12% in the matched cohort.
Tourists had a more complex posttransplantation course with a higher incidence of acute rejection and severe infectious complications.
Clinical Journal of the American Society of Nephrology 11/2008; 3(6):1820-8. · 5.07 Impact Factor