Time to second kidney transplantation in young adults after failed pediatric kidney transplant.

BACKGROUND: Under the current kidney allocation system, pediatric candidates listed prior to age 18 receive priority for high-quality deceased donor organs. This has resulted in a decline in living donor transplantation in pediatrics, despite superior outcomes of living donor transplantation. Due to a young age at transplantation, most pediatric kidney transplant recipients require re-transplantation. The effects of a previously failed deceased donor vs a previously failed living donor on re-transplant candidates are unknown. METHODS: Using the United Network for Organ Sharing database, we examined 2772 re-transplant recipients aged 18-30 years at time of relisting for second KT from 2000 to 2018 with history of prior pediatric KT (age ≤ 18 years). RESULTS: PFLDKT recipients compared to those with PFDDKT had shorter median waiting times and dialysis time regardless of their second donor type (14.0 vs 20.3 months, and 19.1 vs 34.5 months, respectively). PFLDKT recipients had higher re-transplant rates (adjusted HR 1.17, 95% CI 1.09-1.27, and adjusted HR 1.05, 95% CI 0.95-1.15 when calculating from time of relisting and time of returning to dialysis, respectively). PFDDKT recipients were more likely to have higher median PRA levels (90% vs 73%). CONCLUSIONS: Re-transplant candidates who received a previous deceased donor as a child had a higher level of sensitization, longer waiting time, and dialysis exposure compared to those with PFLDKT. Among primary pediatric kidney transplant candidates, consideration should be considered for living donor transplantation, despite the priority for deceased donor organs, to avoid increased sensitization and longer waiting times for with re-transplantation.

Wound-healing effect of adipose stem cell-derived extracellular matrix sheet on full-thickness skin defect rat model: Histological and immunohistochemical study.

The potential use of extracellular matrix (ECM) as a source of wound dressing material has recently received much attention. The ECM is an intricate network of various combinations of elastin, collagens, laminin, fibronectin, and proteoglycans that play a key role in stimulating cell proliferation and differentiation. We evaluated the efficacy of an ECM sheet derived from human adipose tissue as a wound dressing material to enhance healing. We prepared a novel porous ECM sheet dressing scaffold from human adipose tissue. in vitro analysis of the ECM sheets showed efficient decellularisation; absence of immunostimulatory components; and the presence of a wide number of angiogenic and bioactive factors, including collagen, elastin, and proteoglycans. To evaluate in vivo efficacy, full-thickness excisional wounds were created on the dorsal skin of a rat, and the ECM sheets; secondary healing foam wound dressing, Healoderm; or a conventional dressing were applied to each wound site. Photographs were taken every other day, and the degree of reepithelialisation of the wounds was determined. Application of an ECM sheet dressing enhanced the macroscopic wound-healing rate on days 4, 7, and 10 compared with that in the control group. Microscopic analysis indicated that the reepithelialisation rate of the wound was higher in the ECM group compared with that in the control group; the reepithelialisation rate was better than that of the secondary healing foam wound dressing. Moreover, a denser and more organised granulation tissue was formed in the ECM sheet group compared with that in the secondary healing foam wound dressing and control groups. The ECM sheet also showed the highest microvessel density compared with the secondary healing foam wound dressing and control groups. Based on these data, we suggest that a bioactive ECM sheet dressing derived from human adipose can provide therapeutic proteins for wound healing.

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.

Combined liver-kidney transplantation is preferable to liver transplant alone for cirrhotic patients with renal failure.

BACKGROUND: The role of combined liver-kidney transplantation (CLKT) for cirrhotic patients with renal failure (RF) is controversial. Since the model for end-stage liver disease era, there has been a rise in the number of CLKT. Using the Organ Procurement Transplant Network/United Network for Organ Sharing database, this study was undertaken to compare outcomes of cirrhotic patients with RF who received either liver transplant alone (LTA) or CLKT between 2002 and 2008. METHODS: Analysis was limited to cirrhotic patients 18 years old or older, with serum creatinine level 2.5 mg/dL or higher at the time of orthotopic liver transplantation (OLT) or who received dialysis at least twice during the week before OLT. Patients who received CLKT were categorized based on the cause of their underlying RF. RESULTS: Overall liver allograft and patient survival rates of LTA patients were significantly lower compared with CLKT patients (P<0.001). CLKT patients with hepatorenal syndrome showed significantly higher patient and liver allograft survival rates. Liver allograft survival was superior among CLKT patients irrespective of whether they received dialysis. Prevalence of posttransplantation RF was higher for LTA patients at 6 months and 3 years of follow-up (P<0.001). LTA was a significant risk factor both for graft loss and mortality. Recipient hepatitis C virus seropositivity, donor age, donor cause of death, and life support at the time of OLT were also risk factors for graft loss and death. CONCLUSIONS: Cirrhotic patients with RF, in particular with hepatorenal syndrome, CLKT is preferable to LTA because it improves liver allograft and patient survival.

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.

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.

Outcomes after lung transplantation and practices of lung transplant programs in the United States regarding hepatitis C seropositive recipients.

BACKGROUND: The estimated prevalence of hepatitis C virus (HCV) infection among lung transplant (LT) recipients is 1.9%. Many thoracic transplant programs are reluctant to transplant HCV-seropositive patients due to concerns of hepatic dysfunction caused by immunosuppression. The aims of this study are to survey current practices of US LT programs regarding HCV-seropositive patients and using the Organ Procurement and Transplantation Network/United Network for Organ Sharing database and to assess the clinical outcomes of HCV-positive compared with HCV-negative LT recipients. METHODS: A survey of US transplant centers that have performed more than 100 LTs was conducted. In addition, 170 HCV-seropositive and 9259 HCV-seronegative recipients who received HCV-seronegative donor organs between January 1, 2000, to December 31, 2007, were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Outcome variables including patient survival were compared between the two groups. RESULTS: A total of 64.4% centers responded to the survey. Ten of 29 (34.5%) programs would not consider HCV-seropositive patients for LT. Among the 19 programs that will consider HCV-seropositive patients, only five centers would transplant actively viremic patients. Overall patient survival rates of HCV-seropositive patients were similar to HCV-seronegative patients (84.7% at 1 year, 63.9% at 3 years, 49.4% at 5 years for HCV-seropositive group vs. 82.0% at 1 year, 65.0% at 3 years, 51.4% at 5 years for HCV-seronegative group, P=0.712). Relative risk of recipients for death remained statistically insignificant after adjusting for recipient age, donor age, obesity, sensitization, serum creatinine, and medical condition at time of transplant (relative risk [RR]=1.07 [0.84-1.38], P=0.581). CONCLUSIONS: Since 2000, patient survival rates of HCV-positive patients are identical to those who are HCV-negative. However, most of these HCV-seropositive patients were probably nonviremic.

Orthotopic liver transplant using allografts from geriatric population in the United States: is there any age limit?

OBJECTIVES: Observations of minimal pathophysiological changes in the liver with healthy aging represent the rationale for expanding the donor pool with older donors. However, a debate exists for their upper age limit. The aim of this study is to examine the outcomes of orthotopic liver transplants from older patients (>or= 60 years). MATERIALS AND METHODS: Using the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) data, we retrospectively analyzed graft and patient survivals of orthotopic liver transplants done with octogenarian grafts (n=197) and compared them with orthotopic liver transplants done with donors aged between 60 and 79 years (n=4003) and < 60 years (n=21 290) during 2003 to 2007. RESULTS: One- and 3-year graft and patient survival rates among recipients of hepatic allografts from donors < 60 years of age were significantly superior to recipients of octogenarian grafts (graft: 84% vs 75.5% at 1 year; 74.2% vs 61.2% at 3 years; P < .001; patient: 87.8% vs 81.0% at 1-year; 79.3% vs 69.1% at 3 years; P < .001). However, there was no survival difference between recipients of allografts from donors aged > 80 years and 60-79 years (graft: 75.5% vs 77.4% at 1 year; 61.2% vs 64.2% at 3 years; P = .564; patient: 81.0% vs 83.8% at 1 year; 69.1% vs 71.8% at 3 years; P = .494). It correlates well with hepatitis C virus-seronegativity and relatively lower model for end-stage liver disease score among recipients of octogenarian grafts (P < .001). CONCLUSIONS: Careful donor evaluation, avoidance of additional donor risk factors, and their pairing with appropriate recipients offer acceptable functional recovery, even with donors > 80 years.

Induction therapy in pediatric kidney transplant recipients discharged with a triple drug immunosuppressive regimen.

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.

Risk factors for development of new-onset diabetes mellitus in pediatric renal transplant recipients: an analysis of the OPTN/UNOS database.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Impact of hepatitis C infection on outcomes after heart transplantation.

BACKGROUND: Prevalence of hepatitis C infection (HCV) among heart transplant (OHT) recipients ranges from 7% to 18%. Despite the paucity of data regarding the outcomes of heart transplant recipients who are HCV positive before transplant, many transplant centers are declining to perform OHT in HCV-seropositive patients. METHODS: We assessed the clinical outcome of HCV-seropositive compared with HCV-seronegative heart transplant recipients using the Organ Procurement and Transplant Network/the United Network for Organ Sharing database. Between January 1, 2000, and December 31, 2005, 224 HCV-seropositive and 10,406 HCV-seronegative recipients who received HCV-seronegative donor organs were identified. RESULTS: Overall patient survival rates of HCV-seropositive recipients were significantly lower than those of HCV-seronegative recipients (84.8% at 1 year, 77.1% 3 years, 68.9% 5 years for HCV-seropositive group vs. 87.9% at 1 year, 80.7% 3 years, and 74.1% 5 years for HCV-negative recipients, log rank P=0.036). However, adjusted relative risk of recipient HCV-seropositive versus HCV-seronegative status did not reach to statistical significance level (relative risk=1.23 with P=0.087) after adjusting for other donor and recipient factors. Causes of death among HCV-seropositive and HCV-seronegative groups were similar. Cumulative incidence of an acute rejection episode in the first year after transplantation among HCV-seropositive recipients was 35.7% versus 32.6% HCV-seronegative recipients (P=0.32). CONCLUSIONS: A more rational approach should be developed for the management of HCV-seropositive heart transplant candidates. Carefully selected HCV-seropositive patients should not be excluded from OHT.

ASSOCIATION BETWEEN DE NOVO DONOR SPECIFIC HLA ANTIBODY, C4D STAINING IN RENAL GRAFT BIOPSY AND GRAFT OUTCOME: A SINGLE CENTER EXPERIENCE.

In 69 renal transplant recipients (RTR), all had a functioning graft (SCr < 2.0) at one year. After one year, transplant dysfunction was observed and these 69 RTR were biopsied, tested for C4d deposition and donor specific antibodies (DSA). Of these 69 RTR, 29 (42%) showed C4d negativity, 27 (39%) were C4d positive and 13 (19%) were not diagnostic. Forty-nine (71%) recipients had HLA antibodies and 41 (59%) had DSA. The proportion of C4d positivity was significantly higher in patients with DSA (HLA Class I only, II only, and I & II) in comparison to patients without post-transplant HLA antibodies. The incidence of graft failure (including current SCr > 4.0) in RTR with HLA Class II antibodies (Class II only or I & II) was significantly higher than in RTR without post-transplant HLA antibodies (P=0.03).Even after amelioration of rejection, the RTR with Class II DSA group continued to fail beyond 2 years after transplantation when compared with the other 2 groups (None/NDSA or HLA Class I only), however, the difference in graft survival between HLA Class II and None/NDSA groups did not reach statistical significance (log-rank P=0.32). Significant association between C4d staining, post-transplant HLA Class II antibodies and graft failure strongly suggests the importance of post-transplant HLA antibodies. HLA Class II DSAs may be an indicator of chronic allograft nephropathy (CAN) proceeding to graft loss. We propose that amelioration of CAN graft loss may be affected by monitoring and identification of DSA with appropriate immunosuppression of these antibodies.

The evolving notion of "senior" kidney transplant recipients.

The maximum age of recipients expected to benefit with a kidney transplant has increased in the past three decades. In 1980, patients older than age 50 were not listed for a transplant. In 2004, almost 90% aged 50-60 yr with end-stage renal disease were listed, and some were even older than age 80. We summarize previous articles to illustrate how the notion of "senior" has evolved for kidney transplantation, and using data reported to the Organ Procurement Transplant Network, describe characteristics, treatments and outcomes in recipients older than 50 yr. Fractions of male, white, non-obese, unsensitized recipients and use of expanded criteria donors increased in cohorts with increasing recipient age. The percentage of recipients with hypertension or diabetes decreased, but the percentage with cancer increased. The fraction spared steroids increased with increasing age, but other aspects of immunosuppression were not remarkably different. No differences in early outcomes were notable, and elderly recipients likely did not return to dialysis. However, both graft and patient survival rates decreased with increasing age. Although a small fraction was selected, and survival rates were lower, patients older than 80 yr received kidney transplants.

Patient and graft outcomes from deceased kidney donors age 70 years and older: an analysis of the Organ Procurement Transplant Network/United Network of Organ Sharing database.

BACKGROUND: The organ shortage has resulted in more use of older deceased donor kidneys. Data are limited on the impact of donor aged 70 years and older on transplant outcomes. We examined patient and graft outcomes of renal transplant from expanded criteria donors (ECDs) aged 70 years and older, using the Organ Procurement Transplant Network/United Network of Organ Sharing database. METHODS: We identified 601 deceased donor transplants from donors older than 70 years from 2000 to 2005. The follow-up time was until May 2007. Allograft and patient survival were compared between recipients of transplants from older ECDs (age > or =70) and younger ECDs (age 50-69). The relative risk of graft loss and patient death were determined using multivariate models. RESULTS: The adjusted relative risks of overall graft loss (hazards ratio [HR] 1.37; 95% confidence interval [CI] 1.19-1.58), death-censored graft loss (HR 1.32; 95% CI 1.09-1.61), and patient death (HR 1.37; 95% CI 1.15-1.64) were greater among recipients of transplants from older ECD kidneys. The relative risk of patient death was lower when older ECD kidneys were transplanted into recipients older than 60 compared with recipients aged 41 to 60. In contrast, the relative risk of death-censored graft loss was not increased when older ECD kidneys were transplanted into recipients older than 60. CONCLUSIONS: Transplants from older ECD kidneys are associated with a higher risk of graft loss and patient death. The risk was highest when older ECD kidneys were transplanted into recipients younger than 60 years.

Outcomes of dual adult kidney transplants in the United States: an analysis of the OPTN/UNOS database.

BACKGROUND: The organ shortage has resulted in increased use of kidneys from expanded criteria donors (ECD). For ECD kidneys unsuitable for single use, dual kidney transplants (DKT) may be possible. There are limited data comparing outcomes of DKT to single kidney ECD transplants, making it unclear where DKT fits in the current allocation scheme. Our purpose was to compare outcomes of DKT and ECD transplants in the United States. METHODS: From 2000 to 2005, a total of 625 DKT, 7686 single kidney ECD, and 6,044 SCD transplants from donors aged>or=50 years were identified from the Organ Procurement and Transplantation Network/United Network for Organ Sharing data. Allograft survival was the primary outcome. RESULTS: DKT comprised 4% of kidney transplants from donors aged>or=50 years. Compared to the ECD donor group, the DKT donor group was older (mean age 64.6+/-7.7 years vs. 59.9+/-6.2 years) and consisted of more African Americans (13.1% vs. 9.9%), and more diabetic donors (16.3% vs. 10.4%; P<0.001). Mean cold ischemic time was longer in DKT (22.2+/-9.7 hr), but rates of delayed graft function were lower (29.3%) compared to ECD transplants (33.6%, P=0.03). Three-year overall graft survival was 79.8% for DKT and 78.3% for ECD transplants. CONCLUSION: DKT were infrequent and had outcomes comparable to ECD transplants, despite the use of organs from higher risk donors. With a more upfront approach to DKT by offering this option to patients at the time of wait-listing as part of an ECD algorithm, we may be able to further optimize outcomes of DKT and minimize discard of potential organs.

Donor biopsy and kidney transplant outcomes: an analysis using the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database.

BACKGROUND: Although the degree of glomerulosclerosis on pretransplant donor biopsy is one criterion used in the decision to accept a deceased donor kidney, its relationship with graft survival remains controversial. This study compared graft survival with the degree of glomerulosclerosis found on donor biopsy. We also examined the agreement in degree of glomerulosclerosis between paired kidneys. METHODS: Biopsy results from 12,129 adult deceased donor transplants between January 1, 2000 and December 31, 2005 were identified in the Organ Procurement and Transplantation Network/United Network for Organ Sharing data, as of September 11, 2006. Of these, 2696 donors had both kidneys biopsied and subsequently transplanted. RESULTS: Among the groups with greater than 5% glomerulosclerosis, there was no statistically significant difference in graft survival rates (log-rank, P=0.44). The overall graft survival rates of the 0-5% group were significantly superior to those of the >5% groups (1-, 3-, and 5-year rates: 85.9%, 72.4%, and 59.0% for 0-5% group vs. 81.6%, 68.1%, and 53.6% for >5% group, log-rank P<0.001). Agreement between paired kidneys from the same donor was highest for the 0-5% glomerulosclerosis groups (90.6% for pairs with 0-5% glomerulosclerosis in the left kidney vs. 42.5% for pairs with >5% glomerulosclerosis in the left kidney). CONCLUSION: Donor kidneys with less than 6% glomerulosclerosis were associated with better graft outcomes and intrapair agreement in the degree of glomerulosclerosis. Among kidneys with greater than 5% glomerulosclerosis, the degree of glomerulosclerosis did not help predict graft outcomes. Sampling error may contribute to the lack of outcome differences seen among these kidneys, given the low intrapair agreement.

Alemtuzumab induction in deceased donor kidney transplantation.

BACKGROUND: The use of alemtuzumab for induction therapy in kidney transplantation has been increasing. Herein is a report of graft outcomes associated with alemtuzumab induction from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. METHODS: A total of 14,362 deceased donor kidney transplants from 2003 to 2004 received no induction (n=4,364), antithymocyte globulin (ATG; n=4,930), interleukin-2 receptor antagonists (IL-2RA; n=4,378), or alemtuzumab (n=690). Acute rejection within the initial hospitalization, 6 months, and 1 year; graft survival; and rejection-free survival were examined. Graft and rejection-free survival of alemtuzumab recipients maintained with tacrolimus (FK) or cyclosporine (CSA), mycophenolate mofetil (MMF), and steroids versus no calcineurin inhibitors (CNI), MMF, and steroids were compared. RESULTS: Alemtuzumab recipients had less acute rejection during the initial hospitalization (2.3%) than no induction, ATG, and IL-2RA (7.6%, 3.4%, and 4.8%, respectively; P<0.001). There was increased acute rejection at 6 months and 1 year with alemtuzumab (14.5% and 19.2%) compared to no induction (12.7% and 14.8%, P<0.001), ATG (8.2% and 10.2%, P<0.001), and IL-2RA (11.1% and 13.0%, P<0.001) with no difference in adjusted relative risk for graft loss. Alemtuzumab recipients receiving FK or CSA, MMF, and steroids had increased graft (FK/MMF/steroids, P<0.001, CSA/MMF/steroids, P=0.007) and rejection-free survival (FK/MMF/steroids, P<0.001, CSA/MMF/steroids, P=0.006) over 24 months compared to no CNI, MMF, and steroids. CONCLUSIONS: Despite reduced early rejection, acute rejection rates at 6 months and 1 year with alemtuzumab induction exceeded other forms of induction therapy. Maintenance with CNI-based immunosuppression may improve graft and rejection-free survival compared to CNI-free regimens among alemtuzumab recipients.

Comparison of renal allograft outcomes in combined liver-kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: Analysis of UNOS Database.

BACKGROUND: There may be an allograft-enhancing effect by the liver on the renal allograft in the setting of simultaneous combined liver-kidney transplantation (CLKT) from the same donor. This study was performed to investigate whether an existing liver allograft could protect a kidney allograft from immunologic injury due to histoincompatibility in liver transplant recipients who received sequential kidney transplantation (KALT). METHODS: Using the United Network for Organ Sharing database covering January 1996 to December 2003, outcomes of 352 KALT were compared to 1,136 CLKT. Incidence of acute and chronic rejection and rejection-free renal graft survival was compared between two groups. RESULTS: Renal half-life of KALT allografts was shorter than CLKT group (6.6+/-0.9 vs. 11.7+/-1.3 years, P < 0.001). Incidence of chronic rejection in KALT group was higher than CLKT group (4.6 vs. 1.2%, P < 0.001). One and three-year rejection-free renal graft survival of KALT and CLKT groups were different (77% and 67% KALT vs. 85% and 78% CLKT, respectively; P < 0.001). Among human leukocyte antigen mismatched and sensitized patients, rejection-free renal graft survival of KALT group was inferior to the CLKT group (75% at 1 year and 61% 3 years vs. 86% at 1 year and 79% 3 years, P < 0.001). CONCLUSION: Liver allograft provided renal graft immunoprotection if both organs are transplanted simultaneously (immunogenetic identity), but not for kidneys transplanted subsequently.

Waist circumference is the key risk factor for diabetes in Korean women with history of gestational diabetes.

This study investigated relationships between various obesity indices and an onset of type 2 diabetes mellitus (TY2DM) in Korean women with history of gestational diabetes mellitus (GDM). A total of 909 women with history of GDM were enrolled from the four major hospitals, and the first postpartum follow-up examination was made at 6 weeks, and annually thereafter. During postpartum follow-up period, mean 2.13+/-1.75 years, we conducted 2h 75 g OGTT and measured glucose, insulin, c-peptide, lipid profiles, lifestyle and dietary evaluation. For obesity parameters, we measured body weight, body mass index (BMI), waist and hip circumference, subcutaneous fat thickness, body fat percent and weight using bioelectrical impedance tests. Diabetes incidence for 6 years was 12.8% and all the obesity indices were significantly higher in subjects with diabetes or glucose intolerance than those with normal glucose tolerance (p<0.001). When obesity indices were compared between <25th versus >75th percentile, the waist circumference presented with the strongest relationship (odds ratio=5.8, 95% CI 2.8-11.8). This relationship persisted, OR=3.86 (95% CI 1.8-8.2), even after adjusting for the potential confounders. This prospective study revealed that waist circumference is one of the key risk factors for the onset of diabetes in Korean women with history of GDM.

Risk factors for development of new-onset diabetes mellitus after kidney transplantation.

BACKGROUND: New-onset diabetes mellitus after kidney transplantation (NODM) is an important co morbid condition that is associated with inferior graft and patient survival. The objective of this study was to identify donor, recipient and transplant factors, and choices of immunosuppression associated with development of NODM using Organ Procurement Transplant Network/United Network of Organ Sharing database (OPTN/UNOS). METHODS: From January 2004 to December 2005, 15,309 adult kidney transplants alone with at least one follow-up report as of March 2006 were identified in the OPTN/UNOS database. Among these, 1,581 patients developed NODM during the follow-up period. We examined the risk factors of NODM using multivariate Cox regression analysis using the time to diagnosis of NODM as a time-varying end point. Other events such as graft loss, patient death, and lost to follow-up were censored. RESULTS: NODM was reported in 10% in our study population with mean follow-up time of 306 days. After adjusting for other known factors, independent factors associated with the development of NODM included recipient age (29% increase of relative risk [RR] for every 10-year age increment), obesity (RR = 1.39 for body mass index [BMI] 25-30 and RR = 1.85 for BMI > 30 vs. BMI < 25), tacrolimus use (RR = 1.50), hepatitis C virus (HCV) positivity (RR = 1.42), and African-American recipients (RR = 1.32). Alemtuzumab was associated with a lower risk of NODM (RR = 0.52). DISCUSSION: Using OPTN/UNOS database, we identified risk factors for development of NODM. Some of these factors are potentially modifiable, including obesity, HCV infection, and the use of tacrolimus. Clinical trials are needed to assess whether modifying these "modifiable risk factors" will indeed prevent NODM.