Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation.

Perioperative use of probiotics serves as efficient prophylaxis against postoperative infections after liver transplantation, yet data on long-term effects of pre-transplant probiotic intake is lacking. The aim of this study was to assess the effects of pre-transplant probiotic administration on long-term results of liver transplantation. This was secondary analysis of a randomized trial. Patients were randomized to receive either 4-strain probiotic or placebo before liver transplantation. Five year graft survival was set as the primary end-point. Secondary end-points comprised serum bilirubin and C-reactive protein (CRP) concentration, international normalized ratio (INR), serum transaminases and gamma-glutamyl transferase (GGT) activity. Study group comprised 44 patients, of whom 21 received probiotics and 23 received placebo with 5-year graft survival of 81.0% and 87.0%, respectively (p = 0.591). Patients in the probiotic arm exhibited lower INR (p = 0.001) and CRP (p = 0.030) over the first 6 post-transplant months. In the absence of hepatitis B or C virus infection, pre-transplant administration of probiotics also reduced aspartate transaminase activity (p = 0.032). In the intervention arm, patients receiving probiotics for under and over 30 days had 5-year graft survival rates of 100% and 66.7%, respectively (p = 0.061). Duration of probiotic intake > 30 days was additionally associated with increased INR (p = 0.031), GGT (p = 0.032) and a tendency towards increased bilirubin (p = 0.074) over first 6 post-transplant months. Pre-transplant administration of probiotics has mild positive influence on 6-month allograft function, yet should not exceed 30 days due to potential negative effects on long-term outcomes. (ClinicalTrials.gov Identifier: NCT01735591).

Influence of Clonal Plasma Cell Contamination of Peripheral Blood Stem Cell Autografts on Progression and Survival in Multiple Myeloma Patients After Autologous Peripheral Blood Stem Cell Transplantation in Long-term Observation.

BACKGROUND: High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) remains the mainstay of treatment of eligible patients diagnosed multiple myeloma. The role of clonal plasma cell (CPC) contamination was found as a reason for relapse, but results in terms of survival, progression, and purging were ambiguous. Therefore, the aim of the study was to explore the influence of CPC contamination in the autograft on survival and progression after auto-PBSCT. STUDY DESIGN: The study included 59 patients diagnosed and treated for multiple myeloma in 1998-2004. Cells with coexpression of CD38+++CD138++CD56+ and lacking the expression of CD45, CD19, CD10, CD20, and CD23 were considered CPC in flow cytometry. RESULTS: The risk of death and progression after auto-PBSCT increased significantly by 10% (P < .021) and 8% (P < .034) per 1 × 106/kg of the CPC number, respectively. For CPC number above 2.96 × 106/kg overall survival achieved clinical significance. Two years after auto-PBSCT, the risk of death was independent of CPC number among the patients who survived (P = .70). Analogous conclusions concerned results of progression-free survival at 1 year after auto-PBSCT. CONCLUSIONS: High clonal plasma cell contamination (>2.96 ×1 06/kg; 90th percentile of CPC number) is associated with the worst progression-free survival and overall survival. Therefore purging in vitro might be considered for the patients with the highest CPC contamination. Negative consequences of CPC contamination on the risk of death are observed for only 2 years after auto-PBSCT. Thereafter only those patients who had lower CPC contamination survived.

Malnutrition Risk in Kidney Recipients Treated With Mycophenolate Mofetil Is Associated With IMPDH1 rs2278294 Polymorphism.

BACKGROUND: Malnutrition is known to increase morbidity and mortality in renal transplant recipients, whereas little is known about genetic predisposition to low body mass index (BMI) in the transplant setting. Inosine monophosphate dehydrogenase (IMPDH) regulates intracellular fat accumulation, pre-adipicytes maturation, and is a target of mycophenolic acid (MPA) used as a standard immunosuppressant. We hypothesized that MPA may interfere with fat tissue formation and weight gain in kidney transplant recipients and this process may be modified by IMPDH1 or IMPDH2 (genes encoding constitutive and inducible IMPDH) small nucleotide polymorphism variants. STUDY DESIGN: In an observational longitudinal study of kidney transplant recipients treated with mycophenolate mofetil, genetic factors were IMPDH1 (rs2278294, rs2278293) and IMPDH2 (rs11706052) allelic variants, the main outcome was the time-dependent change in BMI, and secondary outcomes were occurrence of BMI below 18.5 or 20 kg/m2. RESULTS: In a study group of 190 patients, no association was found between BMI changes and rs11706052 and rs2278293 variants. In terms of rs2278294, we found that allele G was associated with significantly slower BMI gain in a dominant model of inheritance. Concerning secondary endpoints, none of the AA carriers were underweight at 6 months post-implantation, while at least 2% of G allele carriers were underweight. From the first post-transplant year, all AA carriers had BMI above 20 kg/m2, while among G allele carriers at least 10% had BMI < 20 kg/m2 by generalized estimating equations. CONCLUSION: Based on our results, we postulate that MPA derivates influence post-transplant BMI and potentially also body fat content. In consequence, genotyping rs2278294 would potentially allow clinicians to personalize MPA treatment.

Is Elective Status a Predictor of Poor Survival in Liver Retransplantation?

BACKGROUND: Orthotopic liver retransplantation (reLT) is considered to have poorer outcomes than primary transplantation. The objective of this study was to analyze the impact of medical urgency status as a predictor of patient survival after reLT. METHODS: Forty-nine patients who underwent reLT were included in this retrospective study. Urgent or elective status was based on the judgment of the surgical team, selected variables, and the Model for End-Stage Liver Disease score. Multivariate analysis was performed to identify variables associated with patient survival following reLT. RESULTS: Overall survival of the patient cohort was 57% at 1 year and 54.3% at 3 years after reTL. Survival in urgent-status patients was 68.8% and 63.4% at 1 and 3 years, respectively, whereas the survival rate for elective patients was 40.0% at both time points. Mortality was significantly associated with elective status (hazard ratio [HR], 2.42; P = .046) at 1 year, but was no longer significant (HR, 2.19; P < .069) after 3 years of follow-up. CONCLUSIONS: Elective status is associated with poorer outcome. Patient selection determines long-term survival more than any other single factor, so for patients designated to an elective status, prompt retransplantation should be encouraged.

Association of MYH9 rs3752462 and rs5756168 Polymorphisms With Transplanted Kidney Artery Stenosis.

Allelic variants of the MYH9 gene, encoding myosin nonmuscle heavy chain type IIA, have been shown to correlate with diminished glomerular filtration rates and end-stage kidney disease in individuals of Caucasian ancestry. Myosin nonmuscle heavy chain type IIA is expressed during development as well as in injured vessels and kidney structures. We hypothesized that MYH9 risk variants may correlate with kidney artery injury and dysfunctional healing, such as transplant renal artery stenosis (TRAS). Our study aimed at evaluating the association of MYH9 risk allelic variants (rs4821480, rs4821481, rs3752462, rs11089788, rs136211, rs5756168, rs2032487, and rs2239784) with TRAS, defined as >50% renal artery lumen reduction. Genotyping was performed with the use of custom Taqman genotyping assays on DNA samples (n = 295) from white deceased-donor kidney transplant recipients and genomic DNA from the corresponding donors. Statistical analysis was performed with the use of Kaplan-Meier estimates, log-rank tests, and proportional hazard Cox models. Recipients carrying TT in rs5756168 experienced diminished risk of TRAS (hazard ratio [HR], 0.31; P < .009), whereas organs carrying CC in rs3752462 were exposed to excessive TRAS risk (HR, 2.54; P < .047). In multivariate stepwise analysis TRAS was 10.9-fold increased in kidneys originating from rs3752462 CC, whereas the risk was decreased 3.45-fold (adjusted HR, 0.29) in recipients carrying rs5756168 TT (P < .007 and P < .033, respectively). Intracranial bleeding or trauma compared with other mechanisms of donor death diminished TRAS risk by 87% and 91%, respectively (P < .030 and P < .017). Our study is the first to identify genetic predisposition to transplant renal artery stenosis.

Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis.

BACKGROUND: Changes within the gut microbiota contribute to the progression of chronic liver diseases. According to the results of several studies performed in animal models, gut dysbiosis plays an important role in hepatocarcinogenesis. The aim of this study was to explore the characteristics of gut microbiota associated with the presence of hepatocellular cancer (HCC) in patients with cirrhosis of the liver undergoing liver transplantation. METHODS: A total of 15 patients with HCC and 15 non-HCC patients matched according to etiology of cirrhosis and Model for End-Stage Liver Disease (MELD) scores who underwent liver transplantations between 2012 and 2014 were included. Analysis of their gut microbial profile was based on prospectively collected stool samples from the pretransplant period. RESULTS: Patients with and without HCC were similar with respect to age (P = .506), sex (P = .700), hepatitis C virus (P > .999) and hepatitis B virus (P = .715) infection status, alcoholic liver disease (P > .999), and MELD score (P = .337). Notably, the presence of HCC was associated with significantly increased fecal counts of Escherichia coli (P = .025). Prediction of HCC presence based on E coli counts was associated with the area under the receiver-operating curve of 0.742 (95% confidence interval, 0.564-0.920), with the optimal cutoff on the level of 17.728 (natural logarithm of colony-forming units per 1 g of feces). Sensitivity and specificity rates for the established cutoff were 66.7% and 73.3%, respectively. CONCLUSIONS: The profile of gut microbiota associated with the presence of HCC in cirrhotic patients is characterized by increased fecal counts of E coli. Therefore, intestinal overgrowth of E coli may contribute to the process of hepatocarcinogenesis.

The relevance of intestinal dysbiosis in liver transplant candidates.

BACKGROUND: The gut microbial ecosystem plays an important role in the pathogenesis of liver diseases. However, the association of microbial community structure with the severity of liver dysfunction is not completely understood. METHODS: Fecal microflora was assessed in 40 patients with liver cirrhosis listed for primary liver transplantation (LT). Independent associations between fecal microbial counts and serum bilirubin, serum creatinine, international normalized ratio (INR), and the Model for End-stage Liver Disease (MELD) score were established in multiple linear regression models. RESULTS: Bifidobacterium (standardized regression coefficient [sß] = -0.549; P < 0.001), Enterococcus (sß = 0.369; P = 0.004), and yeast (sß = 0.315; P = 0.018) numbers were independently associated with serum bilirubin, while Escherichia coli counts (sß = 0.318; P = 0.046) correlated with INR, and Bifidobacterium counts (sß = 0.410; P = 0.009) with serum creatinine. Only Bifidobacterium (sß = -0.468; P = 0.003) and Enterococcus (sß = 0.331; P = 0.029) counts were independent predictors of the MELD score. Bifidobacterium/Enterococcus ratio, proposed as a measure of pre-LT gut dysbiosis, was significantly related to the MELD score following the adjustment for the absolute Bifidobacterium (sß = -0.333; P = 0.029) and Enterococcus (sß = -0.966; P = 0.003) numbers. This pre-transplant dysbiosis ratio (PTDR) was significantly correlated with Enterococcus (R = -0.897; P < 0.001) but not with Bifidobacterium (R = 0.098; P = 0.546) counts. Among the other components of gut microflora, only hydrogen peroxide (H2 O2 )-producing Lactobacillus strains significantly influenced Enterococcus counts (sß = 0.349; P = 0.028) and PTDR (sß = -0.318; P = 0.046). CONCLUSION: While the abundance of both Bifidobacterium and Enterococcus is related to liver dysfunction, the size of the Enterococcus population seems to be the most important determinant of pre-LT gut dysbiosis in cirrhotic patients. The H2 O2 -producing Lactobacillus strains potentially ameliorate this dysbiotic state.

Recipient uridine 5'-diphospho-glucuronosyltransferase UGT1A9 c.98T>C variant determines transplanted kidney filtration rate.

Mycophenolic acid preparations are commonly used in prophylaxis of kidney allograft acute rejection. The medication is metabolized by uridine diphosphate glucuronosyltransferases, mainly UGT1A9 present in liver, kidney, and intestine. The effect of UGT1A9 allelic variants on drug metabolism in healthy volunteers and transplant recipients has been previously evaluated; these studies included the UGT1A9 c.98T>C polymorphism (rs72551330, p.Met33Thr) causing methionine-to-threonine substitution in the polypeptide chain. The study objective was to evaluate the relationship between UGT1A9 c.98T>C polymorphism and kidney graft function and survival and the risk of acute allograft rejection. Kidney recipients who underwent transplantation between 2000 and 2007 at the Medical University of Warsaw were included. Clinical data originated from standard medical records, UGT1A9 c.98T>C was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. A group of 243 kidney transplant recipients was enrolled in the study. The frequency of the c.98C allele was 2.4% (12 of 486). Most of the carriers of the allelic variant (10 of 12) received cyclosporine A at transplantation. In the c.98C allele carriers, worse function of the renal allograft, manifested by a significantly lower glomerular filtration rate, was found in the first posttransplantation month and persisted at a lower level for 8 years after the procedure (for comparison of the UGT1A9 c.98 TT vs the UGT1A9 c.98 TC groups, P = .03). No association was found between the presence of the UGT1A9 c.98C allele and the risk of delayed renal graft function, acute rejection, dysfunction of the renal graft, or dialysis treatment reintroduction. Significantly lower estimated glomerular filtration rate of the renal allograft in UGT1A9 c.98C carriers did not translate into decreased allograft survival.

Reliability of frozen section in the assessment of allograft steatosis in liver transplantation.

BACKGROUND: Because liver allograft steatosis is an important risk factor of graft dysfunction after liver transplantation, it must be taken into consideration during graft acceptance. The aim of this study was to evaluate the reliability of frozen section in the assessment of liver steatosis before transplantation. METHODS: The retrospective analysis was based on data of 112 liver allograft procurements performed between 2003 and 2012. Hepatic steatosis was assessed in frozen and routine sections. Sensitivity, specificity, and positive and negative predictive values of the frozen section were evaluated with respect to detection of >30% and >50% steatosis. RESULTS: According to routine section assessment, there were 32 (28.6%) cases of steatosis >30% and 16 (14.3%) of >50%. The results of frozen section assessment were underestimated and overestimated in a similar low number of cases, both for the >30% (0.0% and 0.9%, respectively, P < 1.000) and the >50% (4.5% and 0.9%, respectively, P = .221) cutoff. Sensitivity, specificity, positive and negative predictive values of frozen section assessment were 100.0%, 98.8%, 97.0%, and 100.0%, respectively, for detection of >30% steatosis, and 68.8%, 99.0%, 91.7%, and 95.0%, respectively, for >50% steatosis. CONCLUSIONS: Considering high positive predictive value of frozen section assessment in detection of >50% steatosis, it may serve as a base to discard the use of graft for transplantation. However, according to the relatively moderate sensitivity of this method, decision of graft acceptance must also be made on consideration of other well-known factors for poor posttransplant function.

Outcomes following liver transplantation for metastatic neuroendocrine tumors.

INTRODUCTION: Metastatic disease is generally considered as an absolute contraindication for liver transplantation. However, due to relatively low aggressiveness and slow progression rates, liver metastases from neuroendocrine tumors (NETs) form an exception to this rule. Given the scarcity of available data, the purpose of this study was to evaluate long-term outcomes following liver transplantation for NET metastases. MATERIAL AND METHODS: There were 12 primary liver transplantations in patients with NET metastases out of 1334 liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw) in the period between December 1989 and October 2013. Overall survival (OS) and disease-free survival (DFS) were set as primary and secondary outcome measures, respectively. RESULTS: Median follow-up was 7.9 years. For all patients, OS rate was 78.6% at 10 years and DFS rate was 15.5% at 9 years. Intraoperative transfusions of packed red blood cells (P = .021), Ki-67 proliferative index more than 2% (P = .048), and grade 2 tumors (P = .037) were identified as factors significantly associated with worse DFS. Notably, loss of E-cadherin expression (P = .444), mitotic rate (P = .771), extent of liver involvement (P = .548), primary tumor site (P = .983), and recipient age (P = .425) were not significantly associated with DFS. CONCLUSIONS: Excellent long-term OS rates support liver transplantation for unresectable NET metastases despite almost universal post-transplantation tumor recurrence. Selection of patients with G1 tumors with Ki-67 index not exceeding 2% and reducing the requirement for intraoperative blood transfusions might improve DFS rates.

Uridine diphosphate glucuronosyltransferase 2B7 variant p.His268Tyr as a predictor of kidney allograft early acute rejection.

BACKGROUND: Uridine diphosphate glucuronosyltransferase (UGT2B7) is responsible for conversion of mycophenolic acid to mycophenolic acyl-glucuronide (acylMPAG). Conflicting data exist regarding the role of UGT2B7 p.His268Tyr (802C>T, rs7439366) variant in the clinical course following organ transplantation. STUDY AIM: The aim of this study was to reveal an association between UGT2B7 p.His268Tyr (802C>T, rs7439366) polymorphism and kidney transplantation outcome. STUDY DESIGN, PATIENTS, AND METHOD: Genomic DNA of 235 kidney transplant recipients was genotyped for UGT2B7 802C>T using TagMan single nucleotide polymorphism (SNP) genotyping assay. Maintenance immunosuppression used mycophenolate mofetil (MMF) and cyclosporine A (n = 137) or tacrolimus (n = 98). Primary end-point was biopsy-confirmed acute rejection within 3 and 12 post-transplantation months. Secondary end-points included gastrointestinal side effects, leukopenia, lymphopenia, neutropenia, and infections. Statistical analysis was performed with the aid of SAS System using kernel-smoothed estimates of acute graft rejection hazard function. The log-rank test and hazard ratio were used to reflect association between UGT2B7 802C>T variant and risk of acute graft rejection. RESULTS: Within 3 postimplantation months 38 (16.2%) patients experienced acute rejection; 33 were allele C carriers in UGT2B7 802C>T SNP and 5 were TT homozygotes (P < .0457). Allele C-associated risk of rejection was 2.50 and remained between 2.19 and 3.02 after adjustment for clinical confounders, ie, HLA mismatch, panel-reactive antibodies, donor age, repeated transplantation, induction therapy, donor type, delayed graft function, applied calcineurin inhibitor, or MMF dosing. We found no association between the polymorphism and gastrointestinal side effects, leukopenia, lymphopenia, neutropenia, and infections. CONCLUSION: UGT2B7 802C>T genotyping may help identify patients with excessive early acute rejection risk.

Evaluation of total tumor volume and pretransplantation α-fetoprotein level as selection criteria for liver transplantation in patients with hepatocellular cancer.

INTRODUCTION: Appropriate selection of hepatocellular cancer (HCC) patients for liver transplantation is crucial to minimize the risk of recurrence and provide long-term outcomes comparable with those for other indications. Selection criteria based on total tumor volume (TTV) and α-fetoprotein (AFP) concentrations were proposed in a recent large study. The aim of this study was to evaluate the results of liver transplantation for HCC within and beyond these criteria. MATERIAL AND METHODS: This retrospective study included 104 patients with HCC who underwent liver transplantation. Risk factors for overall survival and tumor recurrence were evaluated. Overall survival and cumulative tumor recurrence rate for patients with TTV <115 cm(3), AFP concentration <400 ng/mL, and no macrovascular invasion (76/104; 73.1%) were evaluated and compared with those for the remaining patients (28/104; 26.9%). RESULTS: Pretransplantation AFP concentration >400 ng/mL (P = .016; hazard ratio [HR], 3.36; 95% confidence intervals [CI], 1.25-9.03) was the only risk factor for overall survival. TTV >115 cm(3) (P = .021; HR 4.29; 95% CI, 1.24-14.81) and AFP concentration >400 ng/mL (P = .002; HR 6.97; 95% CI, 2.02-24.03) were independent risk factors for recurrence. The estimated 3-year tumor recurrence rate was 4.2% for patients with TTV <115 cm(3), AFP concentration <400 ng/mL, and no macrovascular invasion compared with 57.2% for the remaining patients (P < .00001). The 3-year overall survival rate of patients within and beyond this criteria was 81.7% and 64.6%, respectively (P = .0628). CONCLUSIONS: In contrast to other criteria, selection of HCC patients for liver transplantation on the basis of TTV and AFP concentration relates to both morphological features and tumor biology. Although fulfillment of these criteria was more than 1.5-fold higher than that of the Milan criteria, the rate of tumor recurrence was exceptionally low.

Lymphocyte counts in kidney allograft recipients are associated with IMPDH2 3757T>C gene polymorphism.

Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme for de novo synthesis of guanine nucleotides, is required for lymphocyte proliferation. Inhibition of IMPDH by mycophenolic acid (MPA) constitutes part of an immunosuppressive therapy in kidney allograft recipients. The 3757T>C polymorphic variant (rs11706052) of the IMPDH2 gene, which encodes 1 of 2 IMPDH isoenzymes, has been associated with increased IMPDH activity and reduced ability of MPA to exert antiproliferative effects on lymphocytes. The association of IMPDH2 3757T>C SNP with posttransplant courses of kidney allograft recipients remains unclear. Therefore, the aim of the present study was to evaluate associations between this single nucleotide polymorphism and common posttransplant complications among Polish kidney allotransplant recipients. We observed that the frequency of IMPDH2 3757C allele in this group (n=177) did not differ significantly from a control cohort representing the background population of Poland (n=550). There were no significant differences between patients carrying the IMPDH2 3757CT and TT genotypes with respect to acute rejection risk, neutropenia, or incidences of serious infections or gastrointestinal side effects. However, we noted that the 3757C allele was associated with higher lymphocyte counts and a reduced incidence of lymphopenia among kidney allograft recipients. Our findings may be of practical significance to tailor immunosuppressive regimens in kidney transplant recipients.

Moisture-cured silicone-urethanes-candidate materials for tissue engineering: a biocompatibility study in vitro.

This study was performed to verify the response of human bone-derived cells (HBDCs) to moisture-cured silicone-urethanes (mcSUUs) in vitro, as the first step toward using them as scaffolds for bone tissue engineering. Good surgical handling, tissue cavity filling, stable mechanical properties, and potentially improved oxygen supply to cells after implantation justify the investigation of these nondegradable elastomers. A set of various mcSUUs were obtained by moisture-curing NCO-terminated prepolymers, synthesized from oligomeric siloxane diols of two different oligosiloxane chain lengths, and two different diisocyanates (MDI and IPDI), using two different NCO/OH molar ratios. Dibutyltindilaurate (DBTL) or N-dimethylethanolamine (N-met) served as catalysts. After 7 days of culture, cell number, viability, and alkaline phosphatase (ALP) activity were determined, and after 21 days, cell viability and collagen production were determined. Material characteristics significantly influenced the cell response. The mcSUUs prepared with DBTL (widely used in the syntheses of biomaterials) were cytotoxic. The MDI-based mcSUUs were significantly more favored by HBDCs than the IPDI-based ones in all performed tests. MDI-based material with low 2/1 NCO/OH and short chain length was the best support for cells, comparable with tissue-culture polystyrene (with ALP activity even higher). HBDCs cultured on porous scaffolds from this mcSUU produced a tissue-like structure in culture. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Arteriolar hyalinization in implantation kidney biopsies as a predictor of graft function.

The shortage of organs suitable for transplantation has caused a constant evolution of donor acceptance criteria, making an implantation biopsy a valuable tool to predict kidney allograft survival. Preimplantation vascular changes may be divided into sclerosis or intimal fibrous thickening or arteriolar hyalinization. Increasing evidence has indicated their impact on graft function. The aim of this study was to evaluate the significance of preimplantation arteriolar hyalinization for the stability of kidney allograft function. Among a prospective cohort study of 53 kidney recipients (implantation: 2006-2007) who showed serum creatinine values between 1 and 2 mg/dL at 3 months after engraftment, the mean observation time was 24 +/- 8.7 months. At the end of the observation, kidney function as defined by the estimated glomerular filtration rate by the Cockcroft-Gault formula (eGFR C-G) was significantly diminished in individuals with preimplantation evidences of arteriolar hyalinization (mean values: 51.2 +/- 14.8 and 62.0 +/- 16.7, respectively; P < .03) or serum creatinine concentrations (1.76 +/- 0.36 vs 1.51 +/- 0.48 mg/dL; P < .09). The negative influence of arteriolar hyalinosis on allograft function was time-dependent; an early satisfactory filtration rate did not preclude progressive kidney dysfunction.

Microvesicular liver graft steatosis as a risk factor of initial poor function in relation to suboptimal donor parameters.

OBJECTIVE: We sought to examine the role of microvesicular graft steatosis in relation to donor parameters. MATERIALS AND METHODS: We performed 269 consecutive orthotopic liver transplantations (OLT) between 2004 and 2006. Donor parameters of age, body mass index (BMI), intensive care unit (ICU) stay, hypotension, cardiac arrest, pressors, sodium concentration, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), bilirubin, and activated partial thromboplastin time (APTT), as well as the degree of microvesicular graft steatosis were collected into the study. The endpoint of the study was liver graft dysfunction (AST or ALT > 2500 IU/L or prothrombin index < 50% during the first 7 days after OLT). RESULTS: The risk of initial poor function (IPF) at day 7 posttransplantation was significantly related to hepatic microvesicular steatosis (odds ratio [OR] = 1.38 per 1 SD = 9.3%; P < .021). Accounting for the influence of the other donor factors produced little change in the numerical values of relative risk: from 1.22 (following exclusion of GGT) to 1.46 (after elimination of the influence of bilirubin concentration). A 50% increased risk of IPF was equivalent to 12% of the extent of steatosis. CONCLUSION: Microvesicular steatosis is a risk factor for early hepatic dysfunction after OLT.

Multidrug resistance-associated protein 2 gene (ABCC2) variant in kidney allograft recipients.

Multidrug resistance-associated proteins may play crucial roles in the protection of internal organs, particularly the kidneys and liver, from various toxic agents. Little is known about their significance in transplanted organ function and survival. The aim of the present study was to evaluate the frequency of functional ABCC2 4544A>G polymorphism in 165 renal transplant recipients. DNA was isolated from peripheral blood and ABCC2 4544A>G polymorphism was assessed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Analysis of allele and genotype frequencies revealed that the presence of ABCC2 4544 A allele was associated with prolonged observation time and may have an impact on a greater frequency of proteinuria. This observation strongly suggested that particular alleles of the ABCC2 gene may contribute to transplantation outcomes.

Optimal mycophenolic acid and mycophenolic acid glucuronide levels at the early period after kidney transplantation are the key contributors to improving long-term outcomes.

INTRODUCTION: Suboptimal mycophenolic acid (MPA) and its metabolite MPA glucuronide (MPAG) levels are associated with significant increased incidences of graft loss. This study assessed the influence of MPA and MPAG C(0) levels on glomerular filtration rate (GFR) values and histopathologic changes in protocol biopsies of kidney allograft recipients. PATIENTS AND METHODS: This prospective study of 42 low-risk patients receiving mycophenolate mofetil, prednisone, and a low or normal cyclosporine dose included histological assessment, according to the Banff'97 classification, of protocol biopsies before and at 3, 12, and 36 months after transplantation, as well as GFR at 1, 3, 12, 36, and 60 months and MPA enzyme-linked immunosorbent assay, MPAG (HPLC/UV) C(0) levels at 7 days as well as at 1, 3, 12, and 36 months. RESULTS: We observed nonlinear, significant correlations between MPA, MPAG C(0) levels and subclinical rejection episodes (SCR) according to chronic interstitial changes (ci), chronic tubulitis (ct), arteriolar hyalinization (ah) and chronic allograph nephropathy (CAN) indices in protocol biopsies. MPA C(0) levels below 1.0 to 1.5 microg/mL at day 7 were associated with an increased risk of SCR (P < .03), ci > or = 2 (P < .05), CAN > or = 2 (P < .04), and ah > or = 2 (P < .07). MPAG C(0) levels above 100 to 150 microg/mL at day 7 were associated with a decreased risk of ct > or = 2 (P < .01), ci > or = 2 (P < .04), or CAN > or = 2 (P < .04). We also observed a significant linear positive correlation between MPA C(0) level and a significant negative correlation between MPAG C(0) level at 1 month with GFR. CONCLUSION: Optimal MPA and MPAG exposure in the early posttransplant period may improve renal graft outcomes.

Factors predisposing to urinary tract infections in adult kidney allograft recipients with lower urinary tract reconstruction.

OBJECTIVE: Urinary bladder augmentation or urinary diversion may be necessary for successful kidney transplantation in cases of serious urinary tract dysfunction. Patients with reconstructions of the urinary collecting system show noninferior graft survival, although urinary tract infections (UTI) may threaten kidney and recipient survivals. Herein we sought to identify risk factors for serious UTIs in cases of urinary collecting system reconstructions and to evaluate kidney survival and function. PATIENTS AND METHODS: This prospective, case-controlled study included 24 kidney allograft recipients with urinary tract reconstructions who were engrafted from 1999 to 2008. As controls we selected recipients of standard kidney transplants who were matched (1:3) for sex, age, donor type, procedure date, and immunosuppressive regimen. RESULTS: At posttransplantation 33.6 +/- 28 months follow-up, kidney allograft survival was 83% among the reconstructed and 97% among the control groups (P = NS). Kidney allograft function at 3 months in the reconstruction group showed estimated glomerular filtration rate (eGFR) calculated by the Cockcroft-Gault (C-G) equation of 70.4 +/- 20.8 vs 78.8 +/- 19.2 mL/1.73 m(2) in controls (P = .39), and at the end of follow-up, 66.3 +/- 18.1 vs 77.1 +/- 18.9 mL/1.73 m(2), respectively (P = .26). Urinary tract reconstruction patients experienced UTI in 91.7% of cases (n = 22) vs 45.6% in controls (n = 31; P < .0001). A necessity for in-hospital treatment was observed in 67% vs 28% of cases (P < .001). Urosepsis occurred in 4 study patients and 4 controls (P = NS). We observed an increased risk for serious UTI and a trend to diminished graft function (odds ratio [OR] = 1.6 per 10 ml/min of eGFr C-G; 95% confidence interval (CI) 0.97-2.77; P = .055; and OR = 14.7 per 1 mg/dL of serum creatinine; 95% CI 0.61-352.3; P = .097). Another predictor for UTI was cytomegalovirus disease (CMV). CONCLUSION: Kidney recipients requiring urinary tract reconstructions additionally benefit from obtaining the best quality allografts and CMV prophylaxis.

Prediction of graft loss and death in patients with primary sclerosing cholangitis.

BACKGROUND: The prognosis of patients with primary sclerosing cholangitis (PSC) can be accurately determined using the Mayo Clinic Score (MRS), a mathematical model which predicts patient survival. The purpose of our study was to determine the risk of graft loss and/or death among patients who were listed or transplanted because of PSC. PATIENTS AND METHODS: We analyzed the data of 52 patients, who were placed on the transplant list due to PSC between January 2000 and November 2008 and either did or did not undergo liver transplantation (OLT). The primary end point (EP1) of the study was the patient death for any cause. The secondary end point (EP2) was recurrence of PSC or appearance of CCC or death related to the primary liver disease after OLT (PSC recurrence). The observation time was 60 months. According to the calculated MRS, patients were divided into 3 groups: group A (MRS < 0.56); group B (0.56 < or = MRS < 1.56), and group C (MRS > 1.56). The analysis was performed using the LIFETEST and PHREG Procedures of the SAS System. RESULTS: The risk of EP1 occurrence was 2.0 per 1 point of MRS (P < .0006). The risk of EP2 was 2.1 per 1 point of MRS (P < .001). Groups B and C compared with group A showed risks of death of: 0.79 (P = NS) and 6.59 (P < .08), respectively. The percentage of 5-year patient survival rate were 94%, 94%, and 45% according to groups A, B, and C, respectively. CONCLUSION: The risk of death in patients with MRS > 1.56 was 6.59-fold higher than those with MRS < 0.56. MRS > 1.56 significantly decreased 5 year survival among patients with primary sclerosing cholangitis.