Search

In the United States, kidney transplant rates vary significantly across end-stage renal disease (ESRD) networks. We conducted a population-based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1-, 5-, and 10-year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for "healthy" dialysis patients (aged 18-50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow-up of 11 years). Among 23 022 chronic dialysis patients, the 10-year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8-10.7%) to 31.4% (95% CI 16.5-47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2-0.5) to 1.5 (95% CI 1.4-1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Competing events (or risks) preclude the observation of an event of interest or alter the probability of the event's occurrence and are commonly encountered in transplant outcomes research. Transplantation, for example, is a competing event for death on the waiting list because receiving a transplant may significantly decrease the risk of long-term mortality. In a typical analysis of time-to-event data, competing events may be censored or incorporated into composite end points; however, the presence of competing events violates the assumption of "independent censoring," which is the basis of standard survival analysis techniques. The use of composite end points disregards the possibility that competing events may be related to the exposure in a way that is different from the other components of the composite. Using data from the Scientific Registry of Transplant Recipients, this paper reviews the principles of competing risks analysis; outlines approaches for analyzing data with competing events (cause-specific and subdistribution hazards models); compares the estimates obtained from standard survival analysis, which handle competing events as censoring events; discusses the appropriate settings in which each of the two approaches could be used; and contrasts their interpretation., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Antibody-mediated rejection (AMR) is one of the major causes of poor outcomes in ABO-incompatible kidney transplantation (ABOi KT). Studies investigating AMR risk factors found that anti-ABO titer is a major issue. However, the significance of antibody titer has been debated. This retrospective study analyzed AMR risk factors in 59 patients who underwent ABOi KT between August 2010 and January 2015. We also analyzed AMR risk factors in recipients with high anti-ABO baseline titers (≥1:64 on dithiothreitol at 37°C phase or ≥1:256 on antihuman globulin phase). The 2-year patient survival rate was 95.8%, and the 2-year graft survival rate was 94.9%. Nine patients (15.3%) experienced clinical (6 of 59 [10.2%]) or subclinical (3 of 59 [5.1%]) AMR. One patient experienced graft loss from hyperacute rejection. AMR risk factor analysis revealed that baseline antibody titer was associated with incidence of AMR. In patients with high baseline titers, low doses of rituximab (200-mg single-dose), an antibody against CD20, was predictive for AMR. Six patients who received pretransplant intravenous immunoglobulin did not experience AMR even when they had high baseline antibody titers. Our results indicate that a high baseline antibody titer affected the incidence of AMR. ABOi KT candidates with high baseline titers need to undergo an intensified preconditioning protocol, including high-dose rituximab (375 mg/m(2)) and intravenous immunoglobulin., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: As patient and graft survival rates have been improving after kidney transplantation, health-related quality of life (HR-QOL) has become an important indicator of effective treatment. This study aimed to evaluate changes in HR-QOL after kidney transplantation., Materials and Methods: The KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) is a multicenter, observational, 9-year, cohort study. The HR-QOL of patients in the KNOW-KT study was assessed before transplantation and 2 years after transplantation using the Kidney Disease Quality of Life Short Form (KDQOL-SF) including chronic kidney disease targeted area and the Medical Outcome Study 36-item Short Form Health Survey (SF-36). Multivariate linear regression was used to identify significant factors associated with follow-up QOL scores., Results: A total of 175 patients from 8 centers were analyzed. All QOL scores including the total QOL score, chronic kidney disease targeted score, and SF-36 at the 2-year follow-up were significantly increased compared to baseline values. Both physical and mental scale scores were improved after transplantation., Conclusion: The QOL scores for both the mental and physical scales were improved at 2 years after kidney transplantation. High glomerular filtration rate at 2 years, high baseline QOL score, and low body mass index were associated with good follow-up QOL scores. Kidney transplantation for an Asian population with end-stage renal disease can result in better QOL as well as better patient and graft survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We report the case of a renal transplant recipient with pulmonary and splenic mucormycosis whose demise was accelerated by a myocardial abscess. Once pulmonary and splenic mucormycosis was diagnosed, liposomal amphotericin B was started and immunosuppressant treatments were discontinued. The pulmonary cavities regressed during treatment, but new myocardial and peri-allograft abscesses developed. The myocardial abscess diffusely infiltrated the left ventricular wall and was associated with akinesia, which led to sudden cardiac arrest. This case demonstrates a rare manifestation of mucormycosis and highlights the fatality and invasiveness of this infection., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Compliance with immunosuppressive regimens may affect clinical outcomes in renal transplant recipients. The aim of this study was to assess the safety and efficacy of standard-dose tacrolimus modified-release (TAC-MR) once daily versus tacrolimus (TAC) twice daily in stable renal transplant recipients., Methods: Ninety-nine stable renal transplant recipients were randomized to receive standard-dose tacrolimus twice daily or standard-dose modified-release tacrolimus once daily on a 1:1 (mg:mg) basis. The primary end point was the incidence of adverse events (AEs) in both groups. Secondary end points included biopsy-proven acute rejection, graft survival, patient survival, clinical indicators, and change in score of questionnaire., Results: The incidence of AEs was not different between the TAC and TAC-MR groups (56.0% vs 53.1%, P > .05). There were no significant differences in mean calculated glomerular filtration rate, blood pressure, glycosylated hemoglobulin (HbA1c), blood concentration of tacrolimus, and drug compliance. The scores of all items in the 36-item short form health survey (SF-36) were not different between groups, except for vitality. With respect to the subject questionnaire, there was no difference in question scores between the two treatment groups., Conclusion: A regimen of TAC-MR once daily can be considered as an effective and safe alternative formulation of tacrolimus in stable renal transplant patients., (Copyright © 2015. Published by Elsevier Inc.)

The association of hyperuricemia with kidney allograft outcomes remains controversial. We studied this problem in 1170 kidney transplants from January 2000 to December 2010. The primary endpoint was total graft failure (i.e. graft loss or death). Conventional, time-dependent and marginal structural Cox proportional hazards models were fitted, the latter accounting for kidney function as a time-varying confounder affected by prior uric acid levels. Uric acid level was associated with an increased risk of total graft failure in time-fixed and time-varying models (HR 1.02 [95% CI: 1.003-1.04] and HR 1.02 [95% CI: 1.01-1.03], respectively, for every 10 µmol/L increase in uric acid). In contrast, the marginal structural model showed a modestly protective effect (HR 0.90 [95% CI: 0.85-0.94] for every 10 µmol/L increase in uric acid). Similar results were observed for death-censored graft failure and death with graft function. In summary, the absence of a deleterious association between elevated uric acid and graft outcome after accounting for graft function as a time-varying confounder suggests that uric acid is not an independent risk factor for graft failure. The modestly protective effect of uric acid may be an indicator of nutritional status but further study is warranted., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We conducted a nested case-control study from a cohort of adult kidney transplant recipients to assess the risk of transplant glomerulopathy (TG) as a function of donor and recipient HLA-DR and -DQ incompatibility at the eplet level. Cases (n = 52) were defined as patients diagnosed with transplant glomerulopathy based on biopsies showing glomerular basement membrane duplication without immune complex deposition. Controls (n = 104) with a similar follow-up from transplantation were randomly selected from the remaining cohort. HLAMatchmaker was used to ascertain the number of DRB1/3/4/5, DQA1 and DQB1 related eplet mismatches (eplet load). Multivariable conditional logistic regression models demonstrated an increase in the odds of TG (odds ratios [OR] of 2.84 [95% confidence interval (CI): 1.03, 7.84] and 4.62 [95% CI: 1.51, 14.14]) in the presence of 27-43 and >43 HLA-DR + DQ related eplet mismatches versus <27 eplet mismatches, respectively. When the eplet load was modeled as a continuous variable, the OR for TG was 1.25 (95% CI: 1.04, 1.50) for every 10 additional HLA-DR + DQ eplet mismatches. Our study suggests that minimization of HLA-DR + DQ eplet mismatches may decrease the incidence of transplant glomerulopathy diagnosed by indication biopsies. The role of eplet immunogenicity/antigenicity as determinants of allograft outcomes requires further study., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Donor and recipient age in kidney transplantation are known to affect graft and patient survival. To address the question of whether the age difference between donor and recipient impacts on graft survival and death-censored graft survival after transplantation, we examined the impact of age matching (less than 10-year age difference) on the survivals after living donor kidney transplantation., Methods: Two hundred one cases of the primary living donor kidney transplantation were performed and were divided into two groups, age-matched (n = 123) versus age-discrepant (n = 78). Variables included in this study were age, gender, body weight, height, kidney disease, type and duration of dialysis before transplantation, degree of human leukocyte antigen mismatch, ischemic time, graft weight, episode of rejection, type of immunosuppression, recipient serum creatinine after transplantation, and causes of patient death and graft loss., Results: We observed the disparities of graft survival (P = .008) and death-censored graft survival (P = .003) between the groups. One-, 3-, and 5-year death-censored graft survival was 100%, 100%, and 97% in the age-matched group, respectively; and 97%, 90%, and 88% in the age-discrepant group, respectively. By Cox regression multivariate analysis, the variable of age-matching was an independent predictor for both graft survival (ß = 1.325, P = .017) and death-censored graft survival (ß = 2.217, P = .021)., Conclusion: During living donor and recipient matching, age difference between donor and recipient should be minimized., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: A national organ transplant registry is an indispensable organizational requirement for patient care, research, and planning. Even though the Korean Network for Organ Sharing (KONOS) has established a database for a waiting list, organ allocation, and incidence of organ transplantation since 2000, an integrated registry including post-transplantation data is needed for better understanding of organ transplantation. Recently, the Korean Society for Transplantation (KST) and the Korean Center for Disease Control (KCDC) designed a web-based organ transplant registry, named the Korean Organ Transplant Registry (KOTRY). As an initial project of KOTRY, we retrospectively analyzed kidney transplantations (KTs) performed in 2009 and 2010., Methods: A total of 2292 KTs (91.9%) from 46 hospitals (80.7%) were collected and analyzed. Ninety-five elements related to KT were selected and analyzed., Results: Proportions of male recipients and retransplantations were 58.4% and 7.1%, respectively. Even though glomerulonephritis was the most common cause of end-stage renal disease (ESRD) (28.4%), the number of diabetic nephropathy cases was increasing. The living donor (LD) to deceased donor (DD) ratio was 1.69:1. Because of a serious organ shortage in Korea, DD kidneys with a low initial estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m(2) (21.2%) and expanded criteria donors (ECDs; 18.3%) are frequently used. Other noticeable findings are the increasing number of wife donors and ABO-incompatible (ABOi) transplants for O(+) recipients., Conclusions: The epidemiological profile of transplantation is different from country to country. The number of organ transplantations in East Asian countries is rapidly growing, however, there are few epidemiological data about this region in the literature. With the establishment of KOTRY, it was possible to present the first nationwide epidemiological data of Korean KTs., (Copyright © 2014. Published by Elsevier Inc.)

A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio 0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000 person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are reassuring for the safety of living kidney donation., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: An increased incidence of de novo malignancy (dM) is an established complication among solid organ transplant (SOT) recipients compared with the general population. The aims of this study were to describe the incidence and cumulative risk for development of dM among our transplanted population, depending on various clinical and pathologic variables., Methods: We retrospectively reviewed the medical records and pathologic data of SOT recipients performed from February 1995 to December 2010., Results: Among 2673 consecutive SOT recipients, the dM that developed in 66 (2.5%) patients included, 16 (0.6%; 24.2% of overall dM) lymphoid dM and 50 (1.9%; 75.8% of overall dM) nonlymphoid dM. Cumulative incidence of dM in liver was significantly higher than that in kidney transplant recipients. A significantly higher cumulative incidence of dM was observed among living donor versus deceased donor SOT. Although the more frequent development of lymphoid dM was observed during the first year posttransplantation, the cumulative risk of nonlymphoid dM increased year by year, reaching a substantially higher incidence than that of lymphoid dM beyond 5 years after SOT. Comparing the various immunosuppressive regimens, the cumulative incidence was greater among the group with basiliximab induction. However, the hazard of occurrence was unaffected by whether tacrolimus or cyclosporine was used for maintenance immunosuppression. The increased risk of dM was not dependent on recipient age or gender., Conclusion: This study demonstrated distinctive cumulative incidences of dM in different clinical and pathologic settings., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We investigated the effect of the donor kidney weight (Kw) to recipient body weight (Rw) ratio (Kw/Rw) on long-term graft function. To investigate the impact of the Kw/Rw ratio on the graft function, we retrospectively collected data from 213 kidney transplant recipients at least 5 years Post-transplantations. Renal function showed a positive correlation with the Kw/Rw ratio until 5 years after transplantation (at 60 months after transplantation, R = 0.158, P = .023); however, this ratio does not affect graft survival (P = .794). We used the mixed-effect model to identify the factors that affect the estimated glomerular filtration rate (eGFR) over time. In univariate analysis, donor age, BSA, kidney weight, and Kw/Rw ratio were associated with eGFR. To identify independent factors that affect to the eGFR, multivariate analysis using a mixed model was applied. Donor age (P < .001) and Kw/Rw ratio (P < .001) were independent factors that affected the eGFR. To identify the cutoff values of the Kw/Rw ratio and donor age that affect long-term graft function, multiple testing using a mixed model was applied. The cutoff value for the Kw/Rw ratio was 3.16 (P = .0104) and the cutoff value of donor age was 44 years (P = .0001). Based on our results, we conclude that the Kw/Rw ratio and donor age are important factors for the long-term function of graft., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Successful kidney transplantation leads to greater survival and improved quality of life for patients with end-stage renal disease. Among the most important influences on graft outcomes is donor age. We evaluated the relationships between the donor-recipient age gradient (DRAG) and the graft outcomes after deceased-donor kidney transplantation (DDKT)., Methods: From February 1995 to March 2011, a consecutive series of 526 adult DDKT recipients were analyzed. DRAG values were divided into two groups (negative versus positive years) and then four groups (≤-21, -20 to -1, 0 to 20, and ≥21 years)., Results: Median age of donors and recipients were 39 (range, 1-75) and 41 (range, 18-74) years, respectively. The degree of DRAG was not associated with episodes of allograft rejection. High or low DRAG had no effect on posttransplant serum creatinine levels or estimated glomerular filtration rates. However, negative levels of DRAG, particularly less than -20 years, were significantly correlated with superior 10-year death-censored graft survival (86.4% and 83.1% vs 72.2% vs 53.9%; overall P = .031), but not increased overall graft or patient survival., Conclusion: This study demonstrated that DRAG is a prognostic indicator of long-term graft outcomes after DDKT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: This single-center study sought to examine the clinical outcomes of kidney transplant recipients from donors displaying acute kidney injury (AKI)., Methods: We analyzed retrospectively the medical records of the donors and recipients of 54 deceased-donor kidney transplantations performed in our center between March 2009 and March 2012., Results: Among the 54 deceased donors, 36 (66.7%) experienced AKI as determined by the final mean serum creatinine levels measured before graft harvest of 2.66 ± 1.62 mg/dL versus 0.82 ± 0.28 mg/dL among non-AKI donors. The risks of delayed graft function and slow graft function were increased among the AKI versus non-AKI groups in the early post-transplantation period. However, the renal function status of recipients at 3, 6, and 12 months after transplantation was not significantly different between the two groups. Moreover, rejection-free survival rates during the study period were similar. Multivariate analysis revealed an acute rejection episodes (P = .047) and a lower body mass index in the donor relative to the recipient (P = .011) to be independent risk factors predicting poor graft function defined as a 1-year estimated glomerular filtration rate less than 50 mL/min/l.73 m(2). Donor AKI with either a high level (>4.0 mg/dL), an increasing trend of creatinine, or greater severity by the Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) classification was not a significant risk factor., Conclusion: Transplantation of kidneys from the AKI donors, namely, patients with severely decreased renal function, displayed excellent short-term outcomes. Accordingly, kidney transplantations from deceased donors with AKI should be considered more actively to expand the donor pool in Korea., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The BK nephropathy (BKN) shows a 10% prevalence among cases of kidney transplantation (KT). We assessed the incidence of BK replication in KT recipients as well as our updated screening strategy and the impact of interventions on BK virus infections., Methods: Since September 2007, our screening protocol for BK virus included examination of urine cytology or BK virus DNA real-time polymerase chain reaction (PCR) detection on postoperative days 1, 5, 9, 16, 24, 36, 48 weeks up to 1 year. IR present, we tested urine BK virus DNA PCR quantitation. We applied the updated screening protocol from August 2010. It urine BK DNA PCR quantification was above 10(7) copies/mL, we checked regularly blood the BK virus DNA PCR quantification. In addition, if the blood BK virus DNA load was above 10(4) copies/mL and the serum creatinine elevated, we was performed an allograft biopsy. Between September 2007 and December 2011, the 58 recipients who showed BK viremia were enrolled in the present study in 2 groups according to the period of screening protocol (era I, era II)., Results: The time between kidney transplantation and BK viremia detection of era II was shorter than that of era I (16 vs 29 weeks; P = .001). Viremia clearance rate at 6 months in era II was significant higher than that of era I (82% vs 36.8%; P = .001) as well as at 12 months (100% vs 61.1%, P < .001) after intervention. Interestingly, viremia clearance at 12 months after intervention was 100% in era II., Conclusion: An updated screening protocol for BK virus allowed early detection and accurate diagnosis of BKN. Early detection of BK virus infection enabled early intervention and improved viral clearance rate., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: We studied the incidence of vesicoureteral reflux (VUR) in the graft kidney and its effect on the occurrence of urinary tract infection (UTI) and long-term graft function., Methods: We performed a retrospective analysis of 64 adult kidney transplant recipients based upon voiding cystourethrography at 12 months post-transplantation. Patients underwent analysis of survival, incidence of UTIs beyond 1 year, and graft function., Results: Thirty-seven male and 27 female patients in the study populations showed a mean age 42 years. VUR in the transplanted kidney at 12 months post-transplant occurred among 78.1% (50/64) of subjects: grade I (n = 6), grade II (n = 30), or grade III (n = 14) reflux. Patients followed for a median 61 months (range 44-74s) showed 11 cases of UTIs in 9 subjects. There were no significant differences in clinical characteristics or incidence of, UTIs according to the presence or severity of VUR (P = .81) or the Serum creatinine and estimated glomerular filtration rate values at 12, 36, 48, or 60 months post-transplantation., Conclusions: VUR present in 78.1% of patients after kidney transplantation affected neither graft functions or graft survival. The incidence of UTI did not differ according to the presence of VUR., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

The pharmacokinetics, efficacy and safety of once-daily tacrolimus formulation (Tac-OD) were assessed in 34 stable pediatric kidney transplant recipients. Enrolled patients received their dose of twice-daily tacrolimus formulation (Tac-BID) on study Days 0 through 7. On the morning of study Day 8, the total daily doses for patients were converted to Tac-OD on a 1:1 basis and maintained on a once-daily morning dosing regimen. Tacrolimus pharmacokinetic profiles were obtained on study Days 7, 14 and 28 (after dose adjustment). Although the mean C0 concentrations (4.10 ± 1.16-3.53 ± 1.10 ng/mL, p = 0.004), and AUC0-24 (151.8 ± 41.6-129.8 ± 39.3 ng h/mL, p < 0.001) were decreased significantly after a 1:1 based conversion, there was high interindividual variability. The dose of Tac-OD was decreased in 26.5% and increased in 44.1% of patients. The resultant tacrolimus dose and pharmacokinetic profiles on study Day 28 were comparable to those on Day 7. There were no serious adverse events. In conclusion, Tac-BID can be safely converted to Tac-OD in stable pediatric kidney transplant patients with the heightened therapeutic drug monitoring. Effects of drug conversion on the cardiovascular risk factors, neurological side effects and adherence should be further evaluated., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Aging plays a profound role in the ability of the kidney to function. Aging which varies among individuals, has been associated with the matrix metalloproteinase (MMP) 7 and 20 genes. This study was conducted to analyze correlations between polymorphisms of MMP genes [rs880197 in MMP7 (A>T) and rs1711437 in MMP20 (G>A)] and transplant outcomes in 235 recipients., Methods: Transplant outcomes were evaluated according to the sum of the A alleles in the recipients and the donors. The group with a high number of A alleles (≥3) was compared with the group with a low number (<3)., Results: The group with a high number of MMP7 A alleles showed a lower risk of chronic tubulointerstitial lesion than the group with a low number (P = .009). The group with a high number of MMP20 A alleles had showed better long-term kidney function at 10 years after transplantation than the group with a low number (P = .026). Furthermore, the group with a high number of MMP20 A alleles showed a trend toward better graft survival compared with the group with a low number, especially among recipients followed for >1 year (P = .022)., Conclusions: Polymorphisms of MMP7 and MMP20 genes may be surrogate markers to predict long-term outcomes after kidney transplantation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: The use of new selective immunosuppressants as well as the emergence of new antimicrobial resistances raise the use of prophylactic antibiotics as a matter of controversy. The purpose of this study was to retrospectively analyze the clinical significance of prophylactic antibiotics in kidney transplantation., Methods: This retrospective study included 174 renal allograft recipients who were divided into two groups: group A including patients who received perioperative prophylactic antibiotics and group B, who did not receive them. We analyzed who the incidence of infectious complications as well as the causative micro-organisms and their antimicrobial resistance within 1 month after kidney transplantation., Results: Overall bacterial infections were observed during the first postoperative month in 13 cases (7.4%): 6 (3.4%) surgical site 4 (2.3%) urinary tract, 2 (1.1%) bacteremic, and 1 (0.6%) central catheter infections. There was no respiratory infection. The incidence of bacterial infection was not significantly different between the two groups. The major micro-organisms isolated after kidney transplantation, were Staphylococcus aureus and Escherichia coli; both of which had already shown multidrug resistance at the initial time of infection., Conclusion: Not only did use of prophylactic antibiotics have little impact to prevent bacterial infections after kidney transplantation, but also it may induce antimicrobial resistance against the antibiotics used for prophylaxis. Moreover, the increased antibiotic resistance prior to kidney transplantation hampers the effectiveness of prophylactic antimicrobial agents. Guidelines for perioperative antibiotic prophylaxis should be therefore revised., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The present study compared the efficacy and safety of mizoribine (MZR) with mycophenolate mofetil (MMF) in kidney transplantation. This multicenter, randomized clinical trial. Employed doses of study drug tailored to the immunosuppressive need. The primary efficacy outcome was the incidence of biopsy-proven acute rejection episodes (BPAR). The safety of the study drug was assessed using the incidences of adverse events, drug discontinuations, and abnormal laboratory results. The 7 (6.4%) BPARs above grade II were observed in the MZR group noninferior to the 2 (1.8%) in the MMF group (95% confidence interval, -0.007-0.097 > noninferiority limit [-0.2]). BPAR was significantly decreased in the MZR group after the dose change (17/41 [41.4%] vs 8/69 [11.6%]; P < .0001) and the incidence of BPAR was similar between the MZR and MMF groups after the dose change (P = .592). The uric acid level was significantly elevated in the MZR group (P = .002). In conclusion, the efficacy and safety of MZR were similar and statistically noninferior to MMF in combination therapy with tacrolimus., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The outcomes of kidney transplants that simultaneously exhibit donation after cardiac death (DCD) and expanded criteria donor (ECD) characteristics have not been well studied. We examined the outcomes of DCD versus non-DCD kidney transplants as a function of ECD status and the kidney donor risk index (KDRI). A cohort study of 67 816 deceased donor kidney transplant recipients (KTR), including 562 ECD/DCD KTR, from January 1, 2000 to December 31, 2009 was conducted using the Scientific Registry of Transplant Recipients. In a multivariable Cox proportional hazards model, the modestly increased risk of total graft failure in DCD versus non-DCD KTR was not significantly modified by ECD status (hazard ratio1.07 [95% CI: 1.01, 1.15] for non-ECD vs. 1.21 [95% CI: 1.04, 1.40] for ECD, p for interaction = 0.14).Moreover, the hazard ratios did not significantly vary by KDRI quintiles (p = 0.40). Similar trends were seen for death-censored graft failure and death with graft function. In conclusion, ECD status or higher KDRI score did not appreciably increase the relative hazard of adverse graft and patient outcomes in DCD KTR. These findings suggest that the judicious use of ECD/DCD donor kidneys may be an appropriate strategy to expand the donor pool., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all-cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49 ± 18 mL/min/1.73 m(2) . In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m(2) higher eGFR at levels below 45 mL/min/1.73 m(2) was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m(2) . In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Recently, the ImmuKnow assay (Cylex Inc., Columbia, Md) has been reported to be a global immune monitoring tool for organ transplants recipients. We assessed whether immunKnow ATP values predicted infectious syndromes., Methods: We prospectively enrolled 71 kidney transplant patients between September 2008 and May 2011. lmmuKnow assay monitoring was performed at one dav before as well as 4, 8, 12, 16, 20, 24, 36, and 52 weeks after the operation. ImmuKnow assay values were compared as well as BK viral infection pre-infection(PI), at first detection of infectious syndrome (DI), 4 weeks there after (4W), 8 weeks there after (8W) and 12 weeks there after (12W) and pre-recovery (PR), recovery (R) times., Results: Serial ImmuKnow assays showed significant differences over time and BK viral infectious state (P = .026). Interestingly, PI was significantly lower than DI and PR but PR significant greater than PI, 8W and 12W. However, we did not observe an adequate or absolute cutoff value of ImmuKnow by ROC curve: 377 ng/mL ImmuKnow showed 0.471 of AUC and 57.1% and 56.2%, of sensitivity and specificity., Conclusion: Longitudinal evaluation and adjustment of the value of ImmuKnow assay seemed to be a favorable modality to monitor infectious syndromes especially those involving BK virus., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Proteinuria in the nontransplant population is a progressive renal disease. We analyzed the prevalence and clinical significance of proteinuria as well as factors related to its degree at posttransplant year 1 among kidney transplant recipients., Methods: We measured protein in a 24-hour urine among 644 recipients from January 1996 to December 2010., Results: Among 372 male and 272 female recipients, the mean amount of urinary protein was 424.4 ± 1010 mg/d (range, 13.88-8691) including 388 (60.2%) subjects with microproteinuria and the other 256 (39.8%) with overt proteinuria. Nephrotic range proteinuria was observed in 17 (2.6%) and nonnephritic range proteinuria, in 239 (37.1%) recipients. The latter cohort was categorized into low-grade proteinuria (n = 224; 34.8%) and high-grade proteinuria (n = 15; 2.3%). Proteinuria at posttransplant 1 year highly correlated with serum creatinine values at posttransplant years 1 and 2 as well as estimated glomerular filtration rate but not creatinine clearance at postoperative year 2. A greater incidence of graft loss was observed among recipients with more severe proteinuria. Males, recipients with anti-hepatitis C virus antibody, unrelated donors, anti-thymocyte immunoglobulin at the time of reperfusion, maintenance immunosuppression with cyclosporine or without mycophenolate mofetil were strongly associated with the amount of proteinuria., Conclusion: This study demonstrated the prevalence of proteinuria in kidney transplant recipient to be high. The presence as well as level of proteinuria were predictive markers for inferior allograft function., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Although human leukocyte antigen (HLA)-identical renal transplantation achieves superior graft outcomes, it does not uniformly allow indefinite graft survival. Recurrence of the original disease and effects of acute rejection episodes (ARE) may preclude indefinite survival. Herein, we have analyzed the factors that affect the graft outcomes among HLA zero-mismatch cases., Methods: We performed a retrospective, single-center study to evaluate the effect of recurrent glomerulonephritis (GN) and ARE on outcomes of grafts with zero HLA-mismatches (n = 122) versus three to four mismatches (n = 317), and five to six mismatches (n = 102). Forty-one percent of patients had GN as underlying disease., Results: Overall graft survival was 92.4% at 5 years and 79.6% at 10 years. HLA incompatibility did not affect graft survival: zero versus three to four versus five to six mismatches = 92.8% versus 90.8% versus 95.8% at 5 years and 82.5% versus 74.3% versus 85.1% at 10 years, respectively (P = .399). Subgroup analysis for subjects with GN revealed that ARE (P = .001) and recurrent GN (P = .003) were the risk factors for graft loss, whereas living donation was protective (P = .029). ARE was more prevalent with greater HLA incompatibility [0 (reference) < three to four < five to six mismatches; P = .047 and P = .014]. However, recurrent GN showed the opposite trend [0 (reference) > three to four > five to six mismatches; P = .106 and P = .022]. Furthermore, graft loss due to recurrent GN was significant among the HLA zero versus the three- to four-mismatch group (P = .047)., Conclusions: Graft survival was not affected by the degree of HLA incompatibility, which was mainly due to the recurrence of underlying disease. Therefore, a main focus should be the management of recurrence, especially among HLA-identical kidney transplantations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: End-stage renal disease is associated with severe abnormalities in reproductive function. However, the abnormalities are reversed by successful kidney transplantation. The aim of the present study was to compare hormonal levels between recipients with successful kidney transplantations and healthy women with the same gynecologic conditions., Methods: The study group consisted of 31 women of reproductive age with end-stage renal disease who underwent successful kidney transplantation. The ratio of the control group, composed of healthy woman, to the study group was 3:1 matched for age and symptoms., Results: Abnormal bleeding (n = 14) and infertility were the most common gynecologic conditions in kidney transplant recipients. The levels of estrogen (E2) and follicle-stimulating hormone (FSH) in the study group were higher than in the control group, but the levels of progesterone (P4) and luteinizing hormone (LH) were lower in the study group than in the control group. There were no significant differences in prolactin and thyroid-stimulating hormone between the two groups. The incidence of infertility in patients who receive steroid was higher than those with no steroid use (P = .007)., Conclusions: Compared with healthy age- and symptom-matched women, female kidney transplant recipients have increased levels of E2 and FSH and decreased levels of P4 and LH. These differences in hormone profiles may predispose kidney transplant recipients to increased risk of gynecologic pathologies., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Recently, the impact of human leukocyte antigen (HLA) mismatch (MM) on graft outcome has diminished since the introduction of potent immunosuppressive agents, whereas previous reports support the notion that greater numbers of HLA matches are beneficial. This study was undertaken to evaluate outcomes after five or six HLA-mismatched living donor kidney transplantations (LDKT)., Methods: The authors retrospectively reviewed graft function after 2687 LDKTs performed between June 1984 and February 2010. A database of 1364 living related and 1063 living-unrelated donor (LURD) kidney transplantations was used for this study. LURD kidney transplantations were classified into three groups; (1) zero to one HLA MM (n = 158); (2) two to four HLA MM (n = 851); and (3) five to six MM (n = 54). An acute rejection episode was diagnosed based on clinical deterioration of graft function or biopsy findings. Graft survival was calculated using the Kaplan-Meier method., Results: Graft survivals in the zero to one HLA MM, two to four HLA MM, five to six HLA MM, and one-haplo MM LDKT were not significantly different. The rates of acute rejection episodes within 1 year after transplantation were similar irrespective of the HLA MM; (1) zero to one HLA MM (37.3%), (2) two to four HLA MM (35.3%), (3) five to six HLA MM (33.3%; P = .832)., Conclusions: Survival of five or six HLA-mismatched LDKTs was comparable to that of one-haplo MM and relatively well-matched LDKT. The study showed that the presence of five or six HLA MM was not a risk factor for graft survival after LDKT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The best antithymocyte globulin (ATG) preparation for induction suppression in kidney transplant recipients is still not clear. The aim of this study was to identify short- and long-term outcomes in kidney transplant recipients who received thymoglobulin or ATGAM as an induction agent., Methods: We retrospectively reviewed patients who underwent kidney transplantation from 1996 to 2010. Recipients were classified according to the ATG preparation., Results: One hundred fifty-two patients (64.4%) received thymoglobulin and 84 (35.6%) received ATGAM. The occurrence of delayed graft function in patients receiving thymoglobulin was higher than in patients receiving ATGAM (P = .005), but serum creatinine levels and acute rejection after kidney transplantation were not different between the two groups. The death-censored graft survival curve in thymoglobulin recipients was higher than in ATGAM recipients (P = .027). Bacterial infection was a predisposing factor for graft survival (P = .008)., Conclusion: The efficacy of thymoglobulin induction is generally better than that of ATGAM induction, and prevention of bacterial infections was just as important as the use of ATG because bacterial infection was an important risk factor for graft failure., (Copyright © 2012. Published by Elsevier Inc.)

Many studies have explored the participation of cytokines and their genes in renal allograft rejection by using biopsy tissues. To screen for rejection, a biopsy is too invasive to perform without a clinical clue. Therefore, we studied the expression of cytokines that contribute to the early phase of allograft rejection by analyzing mRNA transcripts in sequential blood samples of peripheral blood mononuclear cells (PBMCs) 120 of 6 among patients transplanted before diagnosis of rejection. for comparison with 6 control recipients. The relative expression amount of cytokine genes encoding interleukin (IL) 2, IL-4, IL-10, IL-15, and interferon-γ were assessed using real-time reverse-transcription polymerase chain reactions. IL-2, IL-4, and IL-15 mRNA expressions in clinically stable prerejection phase of the rejection group were significantly higher than those of the control group. In the prerejection samples, the expression of mRNA encoding IL-10 negatively correlated with the expressions of IL-2, IL-4, and IL-15 mRNAs, which were not different from the positive correlations in the postoperative samples from the control group. The expression patterns of IL-2, IL-4, IL-10, and IL-15 genes in PBMCs after transplantation may help to identify acute rejection episodes before clinical deterioration to monitor the efficacy of immunosuppressive treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Enteric-coated mycophenolate sodium (myfortic, Novartis Pharma AG, Basel, Switzerland) is designed to improve the gastrointestinal tolerability of micophenolic acid. This study was designed to evaluate the efficacy and safety of myfortic in Korean de novo renal transplantation. A total of 65 patients from four transplantation centers received the study drug at least once and were included in the intention-to-treat analysis. This study was an open-label, single-arm, multicenter trial with 6-month patient follow-up. Patients received 360 mg (body weight < 50 kg) or 720 mg (body weight > 50 kg) of myfortic per day with tacrolimus and steroids. Induction therapy included basiliximab. The incidence of biopsy-confirmed acute rejection (primary endpoint) within 6 months after transplantation was 7/65 (10.8%). There were 2 (3.1%) graft losses due to severe acute rejection and 1 (1.5%) patient-death due to cardiac arrest. Twenty-two (38.8%) patients experienced gastrointestinal discomfort; however, only 3 (4.5%) cases were associated with an apparent drug reaction. Seventeen (25.4%) patients underwent dose adjustment or myfortic discontinuation during the study period. Patient and graft survival rates at 6 months posttransplantation were 98.1% and 97.0%. Myfortic with tacrolimus-based immunosuppression was efficient and safe after de novo renal transplantation in Korean patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Induction therapy is used to reduce the incidence of acute rejection and to prevent or treat delayed graft function. We compared basiliximab with rabbit antithymocyte globulin (ATG) as induction therapies for kidney transplant recipients., Methods: We retrospectively analyzed the clinical data from 514 patients who received ATG or basiliximab. The patients in the ATG group (n = 152) received ATG (1.5 mg/kg/d) for 5-7 days and those in the basiliximab group (n = 362) were given 2 doses of basiliximab (20 mg) on posttransplantation days 0 and 4. All patients received standard triple immunosuppressive therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids., Results: There were statistically significant differences in the incidences of delayed graft function, 1-year acute rejection rate, death-censored graft survival, and patient survival between the 2 groups, even though the ATG group had more kidney transplants from deceased donors, higher levels of panel reactive antibodies, and more retransplantations. The incidences of cytomegalovirus (CMV) infection and parvovirus infection in the ATG group were higher than those in the basiliximab group. However, there was no statistically significant difference in the incidence of CMV disease between the 2 groups., Conclusions: ATG is safe and efficacious for use in kidney transplant recipients. Our results suggest that ATG should be considered for induction therapy in high-risk patients, such as those who have a kidney allograft from a deceased donor, high levels of panel reactive antibodies, and are undergoing retransplantation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: We initially performed a study to evaluate the safety and efficacy of modified-release tacrolimus (FK506E) in a phase 3, 2-arm, 6-month, randomized, open-label, multicenter trial in Korean living donor de novo kidney transplant recipients. We then performed an extended study to evaluate the long-term safety and efficacy of a FK506E-based regimen up to 45 months posttransplantation in recipients already treated with FK506E., Methods: Initial study was designed as a randomized, open-label, comparative, multicenter study in de novo living donor kidney transplant recipients. The patients were randomized to an FK506E versus a control (FK506) group (1:1). Recipients who completed a 6-month FK506E treatment study were enrolled in the 39-month follow-up study. Primary end-points were patient and graft survivals at posttransplantation 45 months. Secondary end-point was the incidence of a clinical or biopsy-proven acute rejection episode between 6 and 45 months posttransplantation., Results: In the initial 6-month de novo study 124 enrolled patients were randomized into either the FK506E (n = 62) or the control group (n = 62). The incidence of an acute rejection episode was 19.4% (n = 12) in the FK506E versus 16.1% (n = 10) in the control group (P = .638). There was no mortality or graft failure among the 44 recipients enrolled in this additional 39-month follow-up study. There was 1 patient with biopsy-proven acute cellular rejection episode (2.3%) who underwent steroid pulse therapy with renal function recovery. At the time of study completion 40/44 recipients (90.9%) maintained FK506E treatment., Conclusion: This 39-month study following the initial 6-month FK506E study period showed an FK506E-based immunosuppressive regimen in living donor kidney transplantation recipients to be safe and effective., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Cytomegalovirus (CMV) can reactivate causing serious clinical problems during immunosuppression. CMV-specific CD8(+) T cells play an important role in the control of CMV reactivation. Using pentameric major histocompatibility complex (MHC) peptide complexes, we investigated cellular immune responses to CMV among healthy individuals and kidney transplantation recipients in Korea, which is an endemic area of CMV infection., Materials and Methods: Analysis of CMV-specific T cells was performed on 28 healthy individuals and 40 recipients who bore human leukocyte antigen (HLA)-A2 or -A24. CMV pp65 pentamer-binding cells incubated with various monoclonal antibodies were measured by four-color flow cytometry., Results: Detectable levels of pentamer(+) CD8(+) T cells were present in 109/139 samples (78.4%) that stained with the A*02NLV-pentamer, while 15/67 samples (22.4%) stained with the A*24QYD-pentamer (P < .01). Among patients with HLA-A2, 22/24 (91.7%) samples showing positive CMV antigenemia revealed detectable pentamer(+) CD8(+) T cells, while 87/115 (75.7%) displaying negative CMV antigenemia had detectable pentamer(+) CD8(+) T cells (P = .04). There was no significant difference in percentages of pentamer(+) CD8(+) T cells between patients who did versus who did not experience episodes of CMV infection. The subpopulation of CMV-specific CD8(+) T cells in transplantation recipients was evaluated using phenotypic markers; memory cells comprised the majority of the CMV-specific CD8(+) T-cell population., Conclusion: The A*02NLV-pentamer complex was useful to monitor CMV-specific T cells. However, MHC pentamer-based techniques did not provide a clear distinction between patients who are or are not at risk for CMV infection., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Since kidneys from deceased donors with oliguria have not been widely used, compared their outcomes with those in recipients of kidneys without oliguria at the time of organ procurement., Methods: We reviewed the deceased donors and kidney recipients between January 1999 and December 2009, all of whom were defined as standard criteria donors (SCD)., Results: The group included 26 recipients whose terminal serum creatinine level (P < .001), estimated glomerular filtration rates (P < .001), and deceased donor scores (P < .001) were higher than those of the control group. Delayed graft function (P = .044) occurred more often among recipients with donor kidneys with oliguria than those without oliguria, and their hospitalization period was longer (P = .012). The serum creatinine levels in both groups were comparable posttransplantation; there was no significant difference in graft survivals., Conclusion: Deceased donors with oliguria at organ procurement appeared to be poor predictors of outcomes in the early posttransplantation period. Kidneys from deceased donors with oliguria should not be discarded for transplantation. The present study suggested that it is acceptable to use kidneys from selected deceased donors with oliguria., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The use of expanded criteria donor (ECD) kidneys has been encouraged to enlarge the donor pools due to the shortage of donors. However, a major concern with ECD kidneys is poor long-term graft survival. The objective of this study was to determine whether ECD kidneys had a negative impact on graft survival., Methods: We analyzed all deceased donor renal transplantations at our center from September 1995 to December 2009., Results: ECD donors show characteristics, such as comparatively older age, a history of hypertension and diabetes, the use of norepinephrine, high serum creatinine levels and deceased donor scores, and decreased albumin levels and estimated glomerular filtration rates. However, the occurrence of delayed graft function and primary nonfunction among ECD grafts was comparable to those of standard criteria donor (SCD) grafts. Graft survival was not significantly different between the two groups. Only serum creatinine levels at 3, 6, and 9 months after transplantation were lower in the ECD than the SCD group. Multivariate analysis identified longer hospital stay after transplantation, delayed graft function, and acute rejection episodes as independent predictors of poor graft survival., Conclusion: Graft survival of ECD kidney was comparable to that of SCD kidneys. We observed that donor factors prior to procurement were not risk factors for graft failure., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Alemtuzumab (Campath-1H), a humanized monoclonal antibody directed against CD52, is a lymphocyte-depleting agent currently being evaluated as an induction agent in solid organ transplantation. This study analyzed the clinical outcomes and effects on peripheral blood lymphocyte subset counts in adult deceased donor renal transplant recipients who received an alemtuzumab-based induction protocol., Methods: Eleven kidney alone or simultaneous pancreas-kidney transplant recipients received 20 mg alemtuzumab on postoperative days 0 and 1, followed by calcineurin inhibitor-based maintenance immunosuppression after postoperative day 5. We collected 1-year data including recipient and donor demographic features, renal function and adverse events including endocrine impact, incidence of acute rejection episodes, infections or malignancies as well as hematologic and late immunologic parameters for correlation with patient or graft survival., Results: Mean HLA mismatch was 3.6 and 8/11 deceased donors were of the extended criteria type. Only 2 (18%) recipients displayed delayed graft function with a failure of the serum creatinine to decrease by 25% on the first day; however, their long-term outcomes were similar to other nonaffected patients. Serious adverse events were absent; there was no hyperlipidemia or new-onset diabetes. We failed to observe an acute rejection. The 3 (27%) recipients with infectious complications experienced pericardial tuberculosis, urinary tract infection, or invasive pulmonary aspergillosis. Two (18%) cases of posttransplantation lymphoproliferative disease were diagnosed in this study during the follow-up. Overall patient and graft survival rates were both 91%., Conclusion: This study demonstrated that preconditioning with antibody-depletion using alemtuzumab was efficient with satisfactory patient and graft survivals at 1 year. Alemtuzumab induction was safe even for recipients of extended criteria donor renal transplantation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Organ donation after cardiac death (DCD) has been suggested due to the shortage of allografts in Korea. We investigated the outcomes of 446 deceased donor kidney transplant recipients in our center between September 1, 1995, and December 31, 2009. Twenty-four (5.4%) of those patients received DCD kidney grafts. The DCD group had a long intensive care unit stay, frequent inotropics use (such as norepinephrine and dopamine), low mean blood pressure and estimated glomerular filtration rate, and high serum creatinine and deceased donor scores compared to the standard criteria donor (SCD) group and the expanded criteria donor (ECD) group. Mean true warm ischemic time of the DCD group was 59.7 minutes based on asystole time. The DCD group had a long hospital stay after transplantation, but there was no statistically significant difference in delayed graft function and primary nonfunction. Serum creatinine levels at 3 months after transplantation in the ECD and DCD group were significantly higher than the SCD group (P < .001) but lower in the DCD group than in the ECD group at 6 months and 9 months (P < .001 and P = .004) posttransplantation. There were no statistically significant differences in serum creatinine levels or in the graft survival rates between groups at 12 months (P = .160 and P = .737). The use of DCD attracted Korean surgeons because DCD allografts are equivalent to a heart-beating donor. Donors who die during the evaluation of brain death should not be abandoned for procurement, and we need to try to harvest allografts after cardiac death (type 4 DCD) to expand donor pools., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Older living kidney donors are regularly accepted. Better knowledge of recipient outcomes is needed to inform this practice. This retrospective cohort study observed kidney allograft recipients from Ontario, Canada between January 2000 and March 2008. Donors to these recipients were older living (≥ 60 years), younger living, or standard criteria deceased (SCD). Review of medical records and electronic healthcare data were used to perform survival analysis. Recipients received 73 older living, 1187 younger living and 1400 SCD kidneys. Recipients of older living kidneys were older than recipients of younger living kidneys. Baseline glomerular filtration rate (eGFR) of older kidneys was 13 mL/min per 1.73 m² lower than younger kidneys. Median follow-up time was 4 years. The primary outcome of total graft loss was not significantly different between older and younger living kidney recipients [adjusted hazard ratio, HR (95%CI): 1.56 (0.98-2.49)]. This hazard ratio was not proportional and increased with time. Associations were not modified by recipient age or donor eGFR. There was no significant difference in total graft loss comparing older living to SCD kidney recipients [HR: 1.29 (0.80-2.08)]. In light of an observed trend towards potential differences beyond 4 years, uncertainty remains, and extended follow-up of this and other cohorts is warranted., (©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: The aim of this study was to analyze risk factors for delayed graft function (DGF) after deceased donor kidney transplantation and to compare the clinical outcomes of non-DGF versus DGF recipients., Patients and Methods: From January 2004 to June 2008, 75/154 kidneys were transplanted into 74 recipients. We classified the recipients into two groups: group 1 (n=61) without DGF and group 2 (n=13) with DGF., Results: On univariate analysis, recipient age (P=.048) cause of brain death (traumatic brain injury vs disease, P=.016), blood urea nitrogen (P=.002), serum creatinine (P=.001), arterial pH (P=.019), and serum sodium level (P=.012) just before organ procurement showed significant differences. On multivariate analysis, the cause of brain death (P=.015, hazard ratio [HR]: 7.086), the terminal serum creatinine>or=1.5 mg/dL before organ procurement (P=.007, HR: 10.132), and recipient age over >or=50 years (P=.021, HR: 7.767) were independent risk factors for the development of DGF. Graft failures occurred among 5/74 recipients with 5-year graft survivals between group 1 and group 2 of 91.7% and 84.6%, respectively. Patient death occurred in five cases, most by due to infection. The 5-year patient survival between groups 1 and 2 were 93.9% and 84.6%, respectively (P = .106)., Conclusion: The independent risk factors for DGF were the cause of brain death, the terminal creatinine level, and the recipient age. In deceased donor kidney transplantation, DGF may have less effect on long-term patient and graft survivals., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Introduction: The benefit of preemptive kidney transplantation (KTx) for graft survival compared with nonpreemptive KTx is controversial., Objective: To analyze the influence of preemptive KTx on graft survival., Patients and Methods: The study included 476 of 531 patients who had undergone living-donor KTx between January 2000 and June 2007. Pediatric patients and those who had previously undergone KTx were excluded. Recipients were divided into 2 groups; group 1 included 413 patients (86.8%) who received grafts after institution of maintenance dialysis, and group 2 included 63 patients (13.2%) who underwent preemptive KTx., Results: Donor type and HLA mismatch demonstrated significant differences between the 2 groups. Group 1 had more living donors and fewer HLA mismatches. Warm ischemia time in group 2 was significantly shorter than in group 1. The serum creatinine concentration in group 1 on postoperative day 7 was significantly higher than in group 2. Five- and 10-year graft survival in groups 1 and 2, respectively, were 95.3% and 81.3% vs 92.9% and 92.9%. Graft survival was not significant insofar as duration and method of dialysis. At our institution, independent risk factors for graft survival in living-donor KTx are primary end-stage renal disease, acute cellular rejection episodes, and recipient age., Conclusion: We observed no benefit on graft survival in recipients of living-donor KTx insofar as whether they had undergone previous dialysis., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

There is some controversy regarding the exact cytomegalovirus (CMV) antigenemia titer that should be used as a guideline for preemptive anti-CMV therapy. We performed 634 consecutive kidney transplantations between January 2000 and June 2007. Preemptive therapy employed intravenous gancyclovir treatment when the CMV antigenemia titer was >or=50/4x10(5) leukocytes after kidney transplantation. The 634 recipients were allocated into 2 groups according to the peak CMV antegenemia: group A, CMV antigenemia titer<50/4x10(5) (n=550); and group B, >or=50/40x10(5) (n=84). Among the 634 recipients, 264 were positive for CMV antigenemia, and 61 developed symptomatic CMV infections. The incidence of symptomatic CMV infections in group B was significantly higher than in group A. Two cases in both groups developed tissue-proven CMV disease: group A CMV colitis and CMV nephritis, and group B, 2 cases of CMV colitis. Graft and patient survival rates in groups A and B at 5 years posttransplantation were not different. The authors concluded that a CMV antigenemia titer of >or=50/4x10(5) leukocytes can be considered an appropriate guideline for preemptive anti-CMV therapy., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objective: Tacrolimus has been shown to be an important immunosuppressive agent in organ and bone marrow transplantation. Previously, we reported that there were no statistically significant differences between the pharmacokinetic parameters of the oral formulation of generic tacrolimus (TacroBell) and the conventional formulation (Prograf). This study was designed to evaluate the efficacy and safety of oral capsules of TacroBell in de novo renal transplantation., Methods: Ninety-six renal transplant recipients from 9 transplantation centers in South Korea were enrolled between November 2005 and July 2007. De novo renal recipients ranged from 19-65 years old. Ninety-four patients who underwent renal transplantation were administered study drug at least one time in the intent-to-treat (ITT) analysis. This phase 4 clinical trial was a 26-week, open-label, noncomparative, multicenter study., Results: An acute rejection episode developed in 10/94 recipients (10.6%, 95% confidence interval, 4.4%-16.9%). There were no patient deaths during the study. The 6-month graft survival rate was 96.8%., Conclusion: Based on this study, treatment with TacroBell is considered to be efficient and safe after primary renal transplantation.

Invasive pulmonary aspergillosis (IPA) is a serious and lethal complication among organ transplant recipients. This report described the clinical manifestations and treatment of IPA over a 28-year period. From January 1979 to December 2007, 3215 organ transplant patients (2954 kidney and 261 liver recipients) were enrolled in the study. Nine patients developed IPA (7 kidney and 2 liver recipients), yielding an incidence of 0.003% (9/3215). Five IPA patients (55.6%) were diagnosed by transbronchial lung biopsy or autopsy, and 3 (33.3%) by sputum culture study. One patient was diagnosed through clinical manifestations and observations of IPA characteristics on chest X ray. We used amphotericin B (n = 4; 44.4%), voriconazole (n = 2; 22.2%), or fluconazole (n = 1; 11.1%) as the primary antifungal agents, but 2 patients could not receive antifungal agents due to rapid disease progression and sequential mortality. This study showed a high mortality rate among IPA patients (55.6%; 5/9). Only patients who received early antifungal agent thereby after a prompt diagnosis recovered from IPA. This survival advantage warrants careful monitoring for invasive fungal infections after organ transplantation with immediate administration of antifungal agents or surgical intervention.

Upregulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in response to ischemic states has been suggested to have a role in the development of chronic allograft nephropathy. Deposition of C4d in the peritubular capillaries of renal allografts has been reported to be a sensitive marker of acute humoral rejection. The purpose of this study was to determine the effects of HIF-1alpha expression and C4d deposition in implantation biopsies of renal allografts. Implantation biopsies and 22 rejection proved biopsies were performed in 54 renal transplant recipients between December 1996 and July 1999. The mean follow-up was 82.8 months. Immunohistochemical studies were performed using a mouse monoclonal antibody for HIF-1alpha expression and a rabbit polyclonal antibody for C4d detection. HIF-1alpha was demonstrated in 19 of 54 implantation biopsies (35%), and C4d deposition in one (1.9%). The HIF-1alpha-positive group included a higher percentage of deceased donor organs (66.4% vs 17.1%; P = .002) and longer mean cold ischemia times (261.3 +/- 231 vs 103 +/- 40 min; P = .008) compared with the HIF-1alpha-negative group. The relative risks (95% confidence intervals) of expression of HIF-1alpha for allograft rejection, chronic allograft nephropathy, and graft loss were 1.53 (0.82-2.87), 0.61 (0.06-5.50), and 2.45 (0.62-9.85). The C4d-positive patient developed acute accelerated rejection on postoperative day 4. In the present study, the expression of HIF-1alpha showed a significant correlation with the use of a deceased donor kidney and with cold ischemia time. However, there were no significant effects on the prognosis for a graft after implantation of a kidney with HIF-1alpha expression.

In living donor kidney transplantation, initial function of the donor kidneys is split into the remnant kidney and the recipient's implanted kidney. We addressed the questions whether the donor's remnant kidney function increases or decreases after donation and whether the donor's donated kidney is greater or less than that of the recipient's implanted kidney after transplantation. We measured and calculated the functional ratio of each kidney using technetium-99m diethylenetriaminepentaacetic acid (99mTcDTPA) as well as serum creatinine (Scr; mg/dL) and creatinine clearance (Ccr; mL/min/1.73 m2) using 24-hour urines from 100 donors. The Ccr was also calculated using the Cockcroft-Gault formula (Ccr-CG; mL/min/1.73 m2). Within 7 days postnephrectomy, we measured Scr, Ccr, and Ccr-CG of the remnant kidney. For recipients, the Scr, Ccr, and Ccr-CG of the implanted kidney with 24-hour urine were obtained within 7 days posttransplantation. The average Scr, Ccr, and Ccr-CG of the donors were 0.85 +/- 0.17 mg/dL, 110.4 +/- 20.8 mL/min/1.73 m2, and 82.8 +/- 17.3 mL/min/1.73 m2, respectively. After donation, the Ccr and Ccr-CG of remnant kidney increased from 54.5 +/- 11.4 and 40.8 +/- 9.3 mL/min/1.73 m2 to 68.0 +/- 14.3 and 53.6 +/- 11.6 mL/min/1.73 m2, respectively. The recipient Ccr and Ccr-CG of donated kidney also increased from 55.9 +/- 11.8 and 42.0 +/- 9.9 mL/min/1.73 m2 to 78.4 +/- 18.0 and 53.4 +/- 16.4 mL/min/1.73 m2, respectively. Kidney transplantation from a living donor should be encouraged with total functional benefit for both donors and recipients.

Background: Urinary tract infection (UTI) may occur in the form of asymptomatic bacteruria but severe cases may cause life-threatening pyelonephritis or sepsis in immunosuppressed kidney transplant recipients. Vesicoureteral reflux (VUR) is one risk factor in the transplanted kidney. But controversy exists regarding the effect of VUR in terms of graft outcomes. The objective of this study was to analyze the clinical outcomes among patients with posttransplantation VUR., Patients and Methods: Between April 2005 and June 2006, we examined 75 patients with functioning grafts for more than 1 year by voiding cystourethrography at 1 year for the grade of posttransplantation VUR: group A, absent (n = 28) including grade I (n = 6) and II (n = 22); group B, including grade III (n = 17) and IV (n = 2). Patient characteristics included etiology of end-stage renal disease, duration of dialysis before transplantation, serum creatinine, creatinine clearance at 1 and 12 months after transplantation, and postoperative complications. The presence/absence of UTI, acute rejection, and graft loss were compared for significance., Result: Posttransplantation VUR present in 47/75 patients (61.3%) was over grade III in 19 patients. There was no difference in significant risk factors between the groups as well as between the reflux subgroups. VUR did not influence graft function with the only significant factor being acute cellular rejection., Conclusion: We failed to confirm a risk of developing posttransplantation VUR. Posttransplantation VUR did not negatively affect graft function; acute cellular rejection was the only factor that influenced it. Longer follow-up needs to be performed to clarify the long-term effects of posttransplantation VUR on graft function.

Background: In patients undergoing kidney transplantation with a small bladder, many surgeons are faced with technical difficulties about the implantation as well as about satisfactory bladder rehabilitation. The objective of this study was to clarify the clinical outcomes of patients with end-stage renal disease who had a bladder capacity of less than 100 mL on preoperative voiding cystourethrogram after renal transplantation using extravesical ureteroneocystostomy., Patients and Methods: We retrospectively studied 345 patients with end-stage renal disease who underwent renal transplantation between April 2002 and June 2006. These patients were classified into two groups according to their preoperatively estimated bladder capacity using a voiding cystourethrogram. Group A had a bladder capacity of less than 100 mL (n = 23; 6.7%) and group B had a capacity of 100 mL or more (n = 322; 93.3%). For each group, the clinical outcome, including serum creatinine level at 1 month and 1 year after transplantation, bladder capacity, surgical complications, and prevalence of urinary tract infection (UTI) requiring hospital admission were recorded and the graft survival rate calculated., Results: Compared with group B, group A had undergone a longer duration of dialysis and required cadaveric kidney transplantation more frequently (P < .05). Postoperative surgical complications occurred in nine cases. There was no difference in the frequency of surgical complications and UTI requiring hospital admission between group A and group B. At 1 year posttransplant, bladder capacity was 342.0 +/- 43.8 mL (range, 300-400 mL) and 429.1 +/- 75.9 mL (range, 200-500 mL), respectively (P = .015). There was no statistical difference between the groups in the serum creatinine level and the graft survival rate at 5 years after transplantation (100% vs 92.4%)., Conclusions: Similar to patients with a normal bladder size, renal transplantation can be successfully achieved in patients with a small bladder. Attempts to increase the bladder capacity by programmed training of the bladder and bladder expansion by surgical intervention seem unnecessary.

Background: In spite of efforts for simplified and optimal monitoring, variability of cyclosporine (CsA) absorption has shown limited clinical impact. We performed the present study to evaluate the feasibility of C2 monitoring and the optimal target C2 level in Korean recipients., Patients and Methods: Sixty recipients who underwent first living donor kidney transplantations between December 2003 and May 2005 and who were treated with a regimen of CsA, mycophenolate mofetil, and steroid were enrolled in this study. CsA dose was adjusted according to conventional trough levels. Blood samples were collected just before (C0) and at 1, 2, 3, 4, 6, 8, and 12 hours (C1, C2, C3, C4, C6, C8 and C12) after dosing on days 2, 3, and 7 posttransplantation. On days 14 and 28, we determined C0, C1, C2, C3, and C4. We compared CsA levels between a no rejection versus a rejection group., Results: In 8 recipients there were 1 or more acute rejection episodes (13.3%). C2 levels correlated closely with AUC0-4 on each day (r=.892-.944, P<.01), but C2 levels were not significantly different between the no rejection and the rejection group (P>.05). Mean C2 level on days 3 to 28 was significantly different between the 2 groups. (P=.045). One recipient (5.3%) with a mean C2 level greater than 1000 ng/mL underwent acute rejection., Conclusions: CsA concentration monitored as mean C2 levels early posttransplantation rather than a single point concentration on a single day was a predictor of acute rejection in kidney transplantation. Within the first month posttransplantation, the target C2 level is recommended to be over 1000 ng/mL for Korean recipients.