BACKGROUND:Kidney graft torsion and subsequent acute kidney injury is a rare yet potentially devastating complication of intraperitoneal kidney transplant. We report a case of this elusive diagnosis and describe kidney salvage by using laparoscopic fixation.CASE REPORT:A 49-year-old male patient presented with multiple episodes of anuric acute kidney injury 16 months after an uneventful combined orthotopic liver and kidney transplantation. After a thorough investigation, a diagnosis of kidney torsion was made, and the patient was urgently operated. Upon surgery, a complete torsion of a viable kidney was found. Laparoscopic fixation was achieved by using an absorbable mesh "pocket." The patient has experienced no similar episodes in the subsequent year.CONCLUSIONS:Nephrologists and surgeons should be aware of this rare complication. Prompt diagnosis and operative repair are crucial to save the graft. Prophylactic nephropexy should be considered in all intraperitoneal transplantations.

Using living donor organs for sequential liver and kidney transplantation (SeqLKT) in patients with primary hyperoxaluria type 1 (PH1) has emerged as a viable approach. Taking both organs from a single donor, however, is rare. There are 8 reported cases of SeqLKT in the literature, and in all but 1 case, children were the recipients. We present our experience with SeqLKT in 2 young adults with PH1. In the first case, with an interval between procedures of 4.5 months, SeqLKT was performed with a right liver lobe from a 47-year-old father for his 19-year-old son with PH1 who was on dialysis for 2 years before transplantation. Both the donor and the recipient had an uneventful recovery, although there was re-exploration for the control of bleeding in the recipient after liver transplantation. Thirty-three months after transplantation, the patient had normal liver and renal function. In the second case, with an interval between procedures of 22 days, SeqLKT was performed with organs from a 45-year-old father for his 19-year-old daughter with PH1 who was on dialysis for 8 months. The recipient procedures, including right liver lobe transplantation and kidney transplantation, were uneventful. The donor underwent percutaneous drainage of a subphrenic collection and subsequently fully recovered. Eighteen months after transplantation, the recipient's liver and renal allograft function was normal. In conclusion, because of the severe organ shortage, living related SeqLKT using the same donor should be carefully considered for young adults with PH1.

Biliary complications after liver transplantation remain a serious cause of morbidity and mortality. Direct invasive cholangiographic techniques, endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC), have procedure-related complications. Magnetic resonance cholangiopancreatography (MRCP) is non-invasive, safe, and accurate. The aim of this study was to evaluate MRCP in detecting biliary complications following liver transplantation and comparing findings with ERCP and PTC. Twenty-seven consecutive liver transplant recipients who presented with clinical and biochemical, ultrasonographic, or histological evidence of biliary complications were evaluated with MRCP. Patients were followed up for a median period of 36 months. The presence of a biliary complication was confirmed in 18 patients (66.6%): anastomotic biliary stricture in 12 (66.6%); diffuse intrahepatic biliary stricture in 5 (27.7%): ischemic (n = 3), recurrence of primary sclerosing cholangitis (n = 2), and choledocholithiasis in one. In nine patients (33.3%), MRCP was normal. Six patients underwent ERCP, and eight PTC. There was a statistically significant correlation between the MRCP and both ERCP and PTC (p = 0.01) findings. The sensitivity and specificity of the MRCP were 94.4% and 88.9%, respectively, and the positive and negative predictive values, 94.4% and 89.9%, respectively. MRCP is an accurate imaging tool for the assessment of biliary complications after liver transplantation. We recommend that MRCP be the diagnostic imaging modality of choice in this setting, reserving direct cholangiography for therapeutic procedures.

Eisner, S1; Belinki, A2; Geller, A3; Shaharabani, E1; Ben-Ari, Z4; Kniznik, M2; Mor, E1 Author Information

P859 Introduction: New onset post-transplant diabetes mellitus (PTDM) has become increasingly recognized complication of kidney transplantation. Albeit, in the majority of studies during the past decade PTDM rate was found to be significantly higher among patients receiving tacrolimus than cyclosporine, there are major center differences in the reported incidence of PTDM as well as controversy as to the extent of diabetogenicity of tacrolimus (Tac) vs. cyclosporine (Csa). Aim: In this study, we aimed to determine the incidence and dynamics of PTDM in a cohort of consecutive renal transplant recipients remaining on Csa or switched to Tac and followed up for 5 years. Methods: We studied records of all consecutive renal graft recipients (n 107), excluding those with pretransplant diabetes mellitus, transplanted in 1998 and followed up throughout 1998-2003 for new onset of PTDM, defined as de-novo hyperglycemia (glucose >120 mg/dL) treated for more than 1 month. The posttransplant immunosuppression consisted of Csa (Neoral) – started at 10 mg/kg and adjusted to blood levels of 300ng/ml (0-3 mos), 200-250 ng/ml (3-6 mos), 150-200 ng/ml (6-12 mos), 100-150 ng/ml (> 12 mos) or Tac- started at 0.15 mg/kg and adjusted to blood levels of 15-20 ng/ml (0-1 mos), 10-15 ng/ml (1-6 mos), 5-10 ng/ml (>6 mos) given in conjunction with prednisone - 500 mg/d of solumedrol, followed by prednisone 100 mg/d >30 mg/d > 20 mg/d > 10 mg/d tapering over 6 months, azathioprine – at 150 mg/d, or replaced by mycophenolate mofetil - 1.0-2.0 gr/d. The patients were divided into 2 groups: those remaining on Csa (n 43) and those started (n 19) or switched to Tac (n 45). Patient demographics, PRA, HLA match, donor organ parameters, incidence of PTDM, graft and patient survival, and renal function in patients on Csa (Neoral) and Tac were compared, when appropriate, by Wilcoxon Two-Sample, Chi-Square, Fisher’s Exact, T test, Gehan-Wilcoxon, Cox-Mantel, Log rank and Kaplan-Meier tests (SAS statistical software). Results: PTDM was detected in 12/107 patients (11.2%). At the time of its appearance, PTDM prevalence in patients under Tac and Csa -5/50 (10%) and 7/57 (12.2%), respectively was not significantly different (Fisher, Chi test NS). Highest prevalence of new PTDM cases was observed in the first post-transplant year – 11/12 cases (91.7%). In contrast to some previous reports, mellow slope of the PTDM increase was observed on predominantly low-dose FK based protocol after the first year, with the calculated annual elevation of 0.25% in the posttransplant years 2-5. Conclusions: Our results show the PTDM cumulative 5 year incidence of 11.2%. No significant difference in PTDM incidence was found between Csa and Tac treatment (12.2% and 10% over 5 years, respectively). Therefore, it appears that in comparison with Csa immunosuppression, our current, tacrolimus-based protocol is not associated with the increased incidence of PTDM.

Background: Early cholestasis is not uncommon after liver transplantation and usually signifies graft dysfunction. The aim of this study was to determine if serum synthetic and cholestatic parameters measured at various time points after transplantation can predict early patient outcome, and graft function.Methods: The charts of 92 patients who underwent 95 liver transplantations at Rabin Medical Center between 1991 and 2000 were reviewed. Findings on liver function tests and levels of serum bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) on days 2, 10, 30, and 90 after transplantation were measured in order to predict early (6 months) patient outcome (mortality and sepsis) and initial poor functioning graft. Pearson correlation, chi(2) test, and Student's t-test were performed for univariate analysis, and logistic regression for multivariate analysis.Results: Univariate analysis. Serum bilirubin greater than or equal to10 mg/dL and international normalized ratio (INR) >1.6 on days 10, 30, and 90, and high serum ALP and low albumin levels on days 30 and 90 were risk factors for 6-month mortality; serum bilirubin greater than or equal to10 mg/dL on days 10, 30, and 90, high serum ALP, high GGT, and low serum albumin, on days 30 and 90, and INR greater than or equal to1.6 on day 10 were risk factors for sepsis; high serum alanine aminotransferase, INR >1.6, and bilirubin greater than or equal to10 mg/dL on days 2 and 10 were risk factors for poor graft function. The 6-month mortality rate was significantly higher in patients with serum bilirubin greater than or equal to10 mg/dL on day 10 than in patients with values of <10 mg/dL (29.4% vs. 4.0%, p = 0.004). Patients who had sepsis had high mean serum ALP levels on day 30 than patients who did not (364.5 +/- 229.9 U/L vs. 70.8 +/- 125.6 U/L, p = 0.005). Multivariate analysis. Significant predictors of 6-month mortality were serum bilirubin greater than or equal to10 mg/dL [odds ratio (OR) 9.05, 95% confidence intervals (CI) 1.6-49.6] and INR >1.6 (OR 9.11, CI 1.5-54.8) on day 10; significant predictors were high serum ALP level on day 30 (OR 1.005, 1.001-1.01) and high GGT level on day 90 (OR 1.005, CI 1.001-1.01). None of the variables were able to predict initial poor graft functioning.Conclusion: Several serum cholestasis markers may serve as predictors of early outcome of liver transplantation. The strongest correlation was found between serum bilirubin greater than or equal to10 mg/dL on day 10 and early death, sepsis, and poor graft function. Early intervention in patients found to be at high risk may ameliorate the high morbidity and mortality associated with early cholestasis.

P757 Aims: Five doses of daclizumab given initially after kidney transplantation have been shown to reduce acute rejection (AR). Most previous studies with daclizumab were performed mainly in cyclosporine treated recipients and only few were done in patients on tacrolimus-based protocol. The aim of this study was to determine the safety and efficacy of two doses of daclizumab combined with tacrolimus (Tac), mycophenolate mofetil (MMF) and corticosteroids (CS) in prevention of acute rejection in primary kidney allograft. Methods: 25 patients were recruited and randomized into induction (n=11) and control (n=14) groups. All patients received initially 0.15mg/kg of Tac tapered to 0.1mg/kg (mean blood levels 10.9 +/− 2.5 ng/dL at first 3 months, 9.5 +/− 2,9 ng/dL at 6 months and 7.9+/− 2.0 ng/dL at one year), MMF at 2gr/bw/day and CS tapered from 100 to 10 mg/bw/day at 6 month. The induction group received two doses of 1mg/kg daclizumab: before engraftment and on postoperative day 14. All patients received CMV prophylaxis with oral gancyclovir. Patient demographics, PRA status and donor organ characteristics were not significantly different between induction and study group. The mean follow up was 16.8 +/− 4,3 months. Fisher Exact and Student T tests were used as appropriate to compare groups. Results: At one year, biopsy proven AR was diagnosed in 5/14 (35%) of control patients not receiving daclizumab and in none of patients with induction (0/11, 0%) (p 0.05). One patient from control group died from cardiac infarction with functioning renal graft. Delayed graft function, defined as absence of spontaneous reduction of creatinine requiring dialysis support, occurred in 6 out of 14 patients (42.8%) from the control group and in 3/11 (27%) patients treated with daclizumab, p NS. Mean creatinine at one year was 1.47+/−0.8 mg/dL in induction and 1.55+/−0.9 mg/dL in control group (NS), the non censored one year patient and graft survival was 100%/100% and 92.8%/ 85.7% (NS) in daclizumab and control group respectively. There were no adverse effects related to daclizumab administration. The infectious complications (UTI and wound infections) occurred in 5/11 and 9/14 (NS) patients from induction and control groups respectively. Conclusions: Our data suggest that the two doses of daclizumab combined with tacrolimus-MMF-CS protocol is effective in preventing acute rejection, reducing incidence of delayed graft function rate and in maintaining satisfactory graft function. The additional advantages of limited dose daclizumab-tacrolimus combination protocol, could be it’s cost effectiveness as well as lesser likelihood of development of neutralizing anti-daclizumab antibodies.

BACKGROUNDRecent advances in immunosuppressive therapy have led to a substantial improvement in the outcome of kidney transplantation. Living unrelated donors may become a source of additional organs for patients on the kidney waiting list.OBJECTIVESTo study the impact of the combination of calcineurin inhibitors and mycophenolate-mofetile, together with steroids, on outcomes of living related and unrelated transplants.METHODSBetween September 1997 and January 2000, 129 patients underwent living related (n = 80) or unrelated (n = 49) kidney transplant. The mean follow-up was 28.2 months. Immunosuppressive protocols consisted of MMF with cyclosporine (41%) or tacrolimus (59%), plus steroids. Patient and graft survival data, rejection rate, and graft functional parameters were compared between the groups.RESULTSLUD recipients were older (47.8 vs. 33.6 years) with a higher number of re-transplants (24.5% vs. 11.2% in LRD recipients, P < 0.05). Human leukocyte antigen matching was higher in LRD recipients (P < 0.001). Acute rejection developed in 28.6% of LUD and 27.5% of LRD transplants (P = NS). Creatinine levels at 1, 2 and 3 years post-transplant were 1.6, 1.7 and 1.7 mg/dl for LRD patients and 1.5, 1.5 and 1.3 mg/dl for LUD recipients (P = NS). There was no difference in patient survival rates between the groups. One, 2 and 3 years graft survival rates were similar in LRD (91.3%, 90% and 87.5%) and LUD (89.8%, 87.8% and 87.8%) recipients.CONCLUSIONSDespite HLA disparity, rejection and survival rates of living unrelated transplants under current immunosuppressive protocols are comparable to those of living related transplants.

WITH THE SEVERE organ shortage worldwide there has been a trend in recent years toward an increased use of liver allografts from older and otherwise suboptimal donors. The main disadvantage of this donor pool is the increased risk for primary graft non-function (PNF) on initial poor graft function (IPF) after transplantation. Whereas the criteria for retransplantation are well established for patients with PNF recipients with IPF, because of the possibility of full recovery often experience a delay in retransplantatation, which may explain the relatively high mortality rates among recipients with IPF. Several parameters have been proposed as potential prognostic markers for graft survival. Because transplant outcome depends on multiple donor, operative, and recipient factors, most predictive models lack accuracy. For patients with PNF, coagulation function and biochemical parameters are helpful to indicate the need for retransplantation. Severe preservation injury is characterized by cholestasis with rising bilirubin, alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGT) levels that peak at the 10th day posttransplantation. We hypothesized that persistence of abnormalities of these cholestatic parameters beyond day 10 after transplantation may predict subsequent graft loss in patients with IPF.

UNTIL RECENTLY, liver transplantation in patients infected with the hepatitis B virus (HBV) was associated with a high rate of graft loss and poor survival because of viral recurrence. With the use of hepatitis B immune globulin (HBIG), allograft rejection rates have decreased (15% to 50%). However, recurrences still occur due to the saturation of the antibody-binding capacity of HBIG by the high viral load or by mutations in the hepatitis B surface antigen (HBsAg) molecule that render HBIG ineffective. Lamivudine, a purine nucleoside analog that serves as a reverse transcriptase inhibitor, is known to be a potent inhibitor of HBV replication. Lamivudine, administered before and after liver transplantation to prevent graft reinfection, was found to produce a complete and sustained suppression of viral replication. However, lamivudine escape mutations in the YMDD locus of the HBV DNA polymerase have been reported more frequently. Following 52 weeks of therapy post–liver transplantation, Perrillo et al documented a mutation rate of 27%. Our long-term study showed that 62.5% of patients developed lamivudine resistance. The aim of the present study was to determine the efficacy of the combination of HBIG and lamivudine compared with that of HBIG monotherapy to prevent recurrent HBV infection in patients undergoing orthotopic liver transplantation (OLT).

Objectives. Living-unrelated donors may become an additional organ source for patients on the kidney waiting list. We studied the impact of a combination of calcineurin inhibitors and mycophenolate-mofetil together with steroids on the outcomes of living-related (LRD), unrelated (LUR), and cadaver transplantation.Methods. Between September 1997 and January 2000, 129 patients underwent LRD (n = 80) or LUR (n = 49) kidney transplantation, and another 173 patients received a cadaveric kidney. Immunosuppressive protocols consisted of mycophenolate-mofetil with cyclosporine-Neoral (41%) or tacrolimus (59%) plus steroids. We compared the patient and graft survival data, rejection rate, and graft functional parameters.Results. LRD recipients were younger (33.6 years) than LUR (47.8 years) and cadaver (43.7 years) donor recipients (P <0.001). HLA matching was higher in LRD patients (P <0.001). Acute rejection developed in 28.6% of LUR versus 27.5% of LRD transplants and 29.7% of cadaver kidney recipients (P = not significant). The creatinine level at 1, 2, and 3 years after transplant was 1.63, 1.73, and 1.70 mg% for LRD patients; 1.48, 1.48, and 1.32 mg% for LUR patients; and 1.75, 1.68, and 1.67 mg% for cadaver kidney recipients (P = not significant), respectively. No difference in patient survival rates was found among the groups. The 1, 2, and 3-year graft survival rates were significantly better in recipients of LRD (91.3%, 90.0%, and 87.5%, respectively) and LUR transplants (89.8%, 87.8%, and 87.8%, respectively) than in cadaver kidney recipients (81.5%, 78.6%, 76.3%, respectively; P <0.01).Conclusions. Despite HLA disparity, the rejection and survival rates of LUR transplants under current immunosuppressive protocols are comparable to those of LRD and better than those of cadaveric transplants. (C) 2003 Elsevier Inc.

To investigate the association between tacrolimus (TAC) blood concentration and the risk of post-transplantation diabetes mellitus (PTDM) development after living donor liver transplantation (LDLT).This study reviewed the clinical data of 158 adult LDLT recipients. A cut-off of mean trough concentration of TAC (cTAC) value at the sixth month postoperatively was identified using a receptor operating characteristic curve. Other clinical complications rates were compared between different cTAC groups.Thirty-four (21.5%) recipients developed PTDM during follow-up period. Recipients with PTDM suffered lower 1-, 5- and 10-year overall survival rates (85.2%, 64.9%, and 55.6% vs 92.4%, 81.4%, and 79.1%, p < 0.05) and allograft survival rates (87.9%, 76.9%, and 65.9% vs 94.1%, 88.5%, and 86.0%, p < 0.05) than those without PTDM. The best cut-off value of mean cTAC was 5.9 ng/mL. Recipients with higher cTAC (>5.9 ng/mL) were more likely to develop hyperlipidemia (39.6% vs 21.9%, p < 0.05), cardio-cerebral events (7.5% vs1.0%, p < 0.05), and infections (37.7% vs19.0%, p < 0.05) than recipients exposed to low cTAC (≤5.9 ng/mL). However, the two groups showed no difference in the incidence of acute and chronic rejection.Higher mean cTAC at the sixth month postoperatively is related to increased risk of PTDM in LDLT recipients.

De novo tumors (DNT) are a serious complication after orthotopic liver transplantation (OLT), showing a higher overall incidence ranging from 4.7% to 15.7% in non-selected series. Skin cancer (SC) is the most frequent malignancy observed, ranging from 6% to 70% of the tumors observed, followed by post-transplant lymphoproliferative disorders (PTLD) (4.3–30%). Different immunosuppressive protocols do not seem to influence DNT appearance. Colon and upper aerodigestive cancer after OLT seems to be more prone to develop when there are associated risk factors, such as primary sclerosing cholangitis (PSC) and alcoholic liver cirrhosis (ALC). Some risk factors, such as age, smoking, alcohol and others seem to play a role in higher risk for malignancy, but the presence of a long-term immunosuppressive state, more than the specific regimen used, is the basis for this higher incidence. Ethnic and demographic factors are also important variables influencing the heterogeneity of the results, especially influencing Kaposi's sarcoma and skin tumors.

BK POLYOMA virus (BKV) is a newly described agent causing renal dysfunction and failure among kidney transplant recipients. The virus remains latent following primary exposure at childhood and becomes activated in immunocompromised states. Clinically, the virus rarely causes symptoms such as hemorrhagic cystitis in bone marrow transplant recipients. Although viral shedding is detected in urine specimens of many renal transplant recipients, only a few will develop BKV transplant nephropathy. This disease process is characterized by a rapidly progressive loss of graft function. Introduction of new and more aggressive immunosuppressive protocols may explain the emergence of this new infectious complication. We describe our experience with 7 patients with BKV nephropathy with specific attention to possible risk factors.

To validate the feasibility and tolerance of an intensive rehabilitation protocol initiated during the postoperative period in an intensive care unit (ICU) in liver transplant recipients.Prospective randomized study.ICU.Liver transplant recipients over a period of 1 year (N=40).The “usual treatment group” (n=20), which benefited from the usual treatment applied in the ICU (based on physician prescription for the physiotherapist, with one session a day), and the experimental group (n=20), which followed a protocol of early and intensive rehabilitation (based on a written protocol validated by physicians and an evaluation by physiotherapist, with 2 sessions a day), were compared.Our primary aims were tolerance, assessed from the number of adverse events during rehabilitation sessions, and feasibility, assessed from the number of sessions discontinued.The results revealed a small percentage of adverse events (1.5% in the usual treatment group vs 1.06% in the experimental group) that were considered to be of low intensity. Patients in the experimental group sat on the edge of their beds sooner (2.6 vs 9.7d; P=.048) and their intestinal transit resumed earlier (5.6 vs 3.7d; P=.015) than patients in the usual treatment group. There was no significant difference between the 2 arms regarding length of stay (LOS), despite a decrease in duration in the experimental group.The introduction of an intensive early rehabilitation program for liver transplant recipients was well tolerated and feasible in the ICU. We noted that the different activities proposed were introduced sooner in the experimental group. Moreover, there is a tendency to decreased LOS in the ICU for the experimental group. These results now need to be confirmed by studies on a larger scale.

Liver transplantation is the treatment of choice for end-stage liver disease. During the past 8 years we performed 102 liver transplants in 84 adults and 16 children. In the adults, 9 were combined transplants: 1 a liver-pancreas transplant for type I diabetes, and 8 liver-kidney transplants. In the children, transplants included 5 whole-livers, 5 left-lateral liver segments from living-related donors, 4 reduced-grafts of right or left lobes, and 2 split left-lateral segments. At a mean follow-up of 31 months (range 1-96) 70 were alive, 3 had died during surgery and 15 during the first postoperative months. Mortality was due to primary graft non-function (7), sepsis (10), intracranial hemorrhage (1), tumors (4), recurrent hepatitis B (2), biliary strictures (2) and chronic rejection (1). The 1- and 4-year survival rates were 79.5% and 69.6%, respectively. After transplantation, 10 developed biliary stricture (5 corrected by balloon dilatation) and 8 anastomotic stricture (7 corrected by surgery), and there were 2 multiple intrahepatic strictures. There was hepatic artery thrombosis in 5, including 4 children. In 3, grafts were salvaged by thrombectomy and 2 others underwent re-transplantation. In those who survived transplantation by more than 1-month, recurrent hepatitis B was seen in 6 of 17 (35%) and recurrent hepatitis C in 12 of 19 (63%). Thus, results of our first 100 liver transplants are similar to those reported by larger centers, showing that in an appropriate setting good results can be achieved by small transplant programs.