Marcelo Santos Sampaio

Associations of Body Mass Index and Weight Loss with Mortality in Transplant-Waitlisted Maintenance Hemodialysis Patients

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.

Posttransplant malignancies in solid organ adult recipients: an analysis of the U.S. National Transplant Database.

Background De novo posttransplant malignancy (PTM) is a serious complication of transplantation. Incidences may vary among solid organ transplantations (SOTs) and may take to particular screening recommendations and posttransplantation care. Methods Adult recipients, from the U.S. Organ Procurement Transplant Network/United Network for Organ Sharing database (data as of September 3, 2010), of a primary kidney transplantation (KT), liver transplantation (LT), heart transplantation (HT) or lung transplantation (LuT) performed in the United States between 1999 and 2008 were selected. Multiple-organ recipients and those whose grafts failed within 2 weeks after transplantation were excluded. The incidence of PTM (in 1000 person-years) was estimated using the Kaplan-Meier product-limit method and compared with SOT and the general population. Results The cohort included 193,905 recipients (123,380 KT; 43,106 LT; 16511 HT; and 10,908 LuT). PTM incidence was 8.03, 11.0, 14.3, and 19.8 in KT, LT, HT, and LuT, respectively. In general, PTM recipients were 3 to 5 years older, mostly whites, and are males in all SOTs. In KT, the type of cancer with the highest incidence was posttransplant lymphoproliferative disorder (PTLD, 1.58%), followed by lung (1.12%), prostate (0.82%), and kidney (0.79%) cancers; in LT, PTLD (2.44%), lung and bronchial (2.18%), primary hepatic (0.91%), and prostate (0.88%) cancers; in HT, lung and bronchial (3.24%) and prostate (3.07%) cancers, and PTLD (2.24%); and in LuT, lung and bronchial cancers (5.94%), PTLD (5.72%), and colorectal cancer (1.38%). PTLD, Kaposi sarcoma, and lung and bronchial cancers were increased in all SOTs, when compared with an older (55- to 59-year-old) population. Conclusions Cancer incidence is different among solid organ transplantations, and ratios may be higher than those in the 55- to 59-year-old population.

Risk factors for new-onset diabetes mellitus in adult liver transplant recipients, an analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing database.

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 ≧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 (≧50 vs. <50 years, hazard ratio [HR]=1.241), African American race (HR=1.147), body mass index (≧25 vs. <25, HR=1.186), hepatitis C (HR=1.155), recipient cirrhosis history (HR=1.107), donor age (≧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.

Associations of Pretransplant Diabetes Mellitus, New-Onset Diabetes After Transplant, and Acute Rejection With Transplant Outcomes: An Analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) Database

BACKGROUND 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. STUDY DESIGN Historical cohort study. SETTING & PARTICIPANTS 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. PREDICTORS 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). RESULTS 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. LIMITATIONS Potential information bias with exposure, covariable, or outcome misclassification; relatively short follow-up. CONCLUSIONS 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.

Obesity Was Associated With Inferior Outcomes in Simultaneous Pancreas Kidney Transplant

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/m2. The cohort was divided in three groups: normal (BMI 18.5–24.9 kg/m2, reference group), overweight (BMI 25–29.9 kg/m2), and obese (BMI 30–40 kg/m2). 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.

Association of immunosuppressive maintenance regimens with posttransplant lymphoproliferative disorder in kidney transplant recipients.

Background. The association of immunosuppressive regimens (ISRs) with posttransplant lymphoproliferative disorder (PTLD) may be related with the Epstein-Barr virus (EBV) recipient serostatus. Methods. We selected primary kidney transplant recipients from Organ Procurement Transplant Network/United Network for Organ Sharing database (2000–2009) who were discharged with a functioning graft and were receiving an ISR including an antiproliferative drug and a calcineurin inhibitor as follows: mycophenolate mofetil (MMF)/mycophenolate sodium+tacrolimus (TAC), MMF+cyclosporine A (CsA); mammalian target of rapamycin inhibitor (mTORi)+TAC; and mTORi+CsA. Adjusted risks of PTLD, rejection, death, and graft failure were examined in all recipients and compared between EBV+ and EBV− recipients. Results. Of 114,025 recipients, 754 developed PTLD (5-year incidence of 0.84%). Adjusted hazard ratio for PTLD was 4.39 (95% CI: 3.60–5.37) for EBV− versus EBV+ recipients; and 1.40 (95% CI: 1.03–1.90) for mTORi+TAC, 0.80 (95% CI: 0.65–0.99) for MMF+CsA, and 0.90 (95% CI: 0.57–1.42) for mTORi+CsA, versus MMF+TAC users. In EBV− recipients, hazard ratio for PTLD was 1.98 (95% CI: 1.28–3.07) for mTORi+TAC, 0.45 (95% CI: 0.28–0.72) for MMF+CsA, and 0.84 (95% CI: 0.39–1.80) for mTORi+CsA users versus MMF+TAC. No difference was seen in EBV+ recipient groups. Rejection rates were higher among MMF+CsA recipients in both EBV groups. Death and graft failure risk were increased in all EBV+ISR groups, while in EBV− these risks were only increased in mTORi+TAC group versus MMF+TAC. Conclusions. In EBV− recipients, immunosuppression with mTORi+TAC was associated with increased risk of PTLD, death, and graft failure, while MMF+CsA use was associated with a trend to increased risk of rejection, lower PTLD risk, and similar risk for graft failure when compared with MMF+TAC.

Intermediate-term outcomes associated with kidney transplantation in recipients 80 years and older: an analysis of the OPTN/UNOS database.

Background. 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. Methods. 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. Results. 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. Conclusion. 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.

Impact of Epstein–Barr virus donor and recipient serostatus on the incidence of post-transplant lymphoproliferative disorder in kidney transplant recipients

BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of transplantation. METHODS Using the OPTN/UNOS database, primary kidney recipients (2000-2009) were stratified according to transplant type (deceased donor, DD or living donor, LD), donor (D) and recipient (R) Epstein-Barr virus (EBV) serostatus (R+; D+/R- and D-/R-) and recipient age. Incidence and adjusted risk of PTLD and death were compared. RESULTS Of the 137 939 primary kidney recipients transplanted between 2000 and 2009, 913 subsequently developed PTLD. In 90 208 recipients with known EBV serostatus, we found a trend toward a decrease in PTLD incidence in years 2007-2009 when compared to 2000-2003. This was due to a significant decrease in PTLD incidence in EBV- recipients. Of those, 61 273 had a known donor serostatus and were further examined. In adults, PTLD incidence (in 1000 person-years) in DD and LD was 7.0 and 7.0 in D+/R-; 3.0 and 2.5 in D-/R- and 1.2 and 1.0 in R+, respectively. The hazard ratio (HR) for PTLD (R+ as reference) in D+/R- (6.2 in DD and 7.2 in LD) was double to thrice than for D-/R- transplants (2.4 in both DD and LD). In pediatric recipients, PTLD incidence in DD and LD was 15.9 and 17.3 in D+/R-; 12 and 18 in D-/R- and 1.2 and 2.2 in R+, respectively. The HR for PTLD was 17.4 and 6.9 in D+/R- and 15.9 and 7.6 in D-/R- in DD and LD, respectively. CONCLUSION A D+/R-, compared with a D-/R- transplant, may contribute to an increase in PTLD incidence of 35 and 42% in adult DD and LD transplants, respectively.

Outcomes of Simultaneous Pancreas-Kidney Transplantation in Type 2 Diabetic Recipients

BACKGROUND AND OBJECTIVES 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 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. RESULTS 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. CONCLUSIONS 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.

Induction Immunosuppressive Therapy in the Elderly Kidney Transplant Recipient in the United States

BACKGROUND AND OBJECTIVES The choice of induction agent in the elderly kidney transplant recipient is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 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. RESULTS 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. CONCLUSIONS 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.