Efficacy and Safety of Everolimus and Mycophenolic Acid With Early Tacrolimus Withdrawal After Liver Transplantation: A Multicenter Randomized Trial

SIMCER was a 6‐mo, multicenter, open‐label trial. Selected de novo liver transplant recipients were randomized (week 4) to everolimus with low‐exposure tacrolimus discontinued by month 4 (n = 93) or to tacrolimus‐based therapy (n = 95), both with basiliximab induction and enteric‐coated mycophenolate sodium with or without steroids. The primary end point, change in estimated GFR (eGFR; MDRD formula) from randomization to week 24 after transplant, was superior with everolimus (mean eGFR change +1.1 vs. ?13.3 mL/min per 1.73 m² for everolimus vs. tacrolimus, respectively; difference 14.3 [95% confidence interval 7.3–21.3]; p < 0.001). Mean eGFR at week 24 was 95.8 versus 76.0 mL/min per 1.73 m² for everolimus versus tacrolimus (p < 0.001). Treatment failure (treated biopsy‐proven acute rejection [BPAR; rejection activity index score >3], graft loss, or death) from randomization to week 24 was similar (everolimus 10.0%, tacrolimus 4.3%; p = 0.134). BPAR was more frequent between randomization and month 6 with everolimus (10.0% vs. 2.2%; p = 0.026); the rate of treated BPAR was 8.9% versus 2.2% (p = 0.055). Sixteen everolimus‐treated patients (17.8%) and three tacrolimus‐treated patients (3.2%) discontinued the study drug because of adverse events. In conclusion, early introduction of everolimus at an adequate exposure level with gradual calcineurin inhibitor (CNI) withdrawal after liver transplantation, supported by induction therapy and mycophenolic acid, is associated with a significant renal benefit versus CNI‐based immunosuppression but more frequent BPAR.     

Renal Transplantation With Final Allocation Based on the Virtual Crossmatch

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor–recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long‐term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor‐specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR <1 year) for FCXM+ (n = 54) and FCXM? (n = 454) recipients. Median follow‐up is 7.1 years. FCXM+ recipients were significantly different from FCXM? recipients for the following risk factors: living donor (24% vs. 39%, p = 0.03), duration of dialysis (31.0 months vs. 13.5 months, p = 0.008), retransplants (17% vs. 7.3%, p = 0.04), % sensitized (63% vs. 19%, p = 0.001), and PRA >80% (20% vs. 4.8%, p = 0.001). Despite these differences, 5‐year actual graft survival rates are 87% and 84%, respectively. AR <1 year occurred in 13% FCXM+ and 12% FCXM? recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor–recipient compatibility.     

Therapeutic doses of neostigmine,depolarising neuromuscular blockade and muscle weakness in awake volunteers: a double‐blind,placebo‐controlled,randomised volunteer study

Neostigmine reverses non‐depolarising neuromuscular blockade, but may cause muscle weakness when administered after full recovery of neuromuscular function. We hypothesised that neostigmine in therapeutic doses impairs muscle strength and respiratory function in awake healthy volunteers. Twenty‐one volunteers were randomised to receive two doses of either intravenous (i.v.) neostigmine 2.5 mg with glycopyrrolate 450 μg (neostigmine group, n = 14) or normal saline 0.9% (placebo group, n = 7). The first dose was administered immediately after obtaining baseline measurements, and the second dose was administered 15 min later. All 14 volunteers in the neostigmine group received the first dose, mean (SD) 35 (5.8) μg.kg^?1, but only nine of these volunteers agreed to receive the second dose, 34 (3.5) ?g.kg^‐1. The primary outcome was hand grip strength. Secondary outcomes were train‐of‐four ratio, single twitch height, forced expiratory volume in 1 s, forced vital capacity, forced expiratory volume in 1 s/forced vital capacity ratio, oxygen saturation, heart rate and mean arterial pressure. The first dose of intravenous neostigmine with glycopyrrolate resulted in reduced grip strength compared with placebo, ?20 (20) % vs. +4.3 (9.9) %, p = 0.0016; depolarising neuromuscular blockade with decreased single twitch height, ?14 (11) % vs. ?3.8 (5.6) %, p = 0.0077; a restrictive spirometry pattern with decreased predicted forced expiratory volume in 1 s, ?15 (12) % vs. ?0.47 (3.4) %, p = 0.0011; and predicted forced vital capacity, ?20 (12) % vs. ?0.59 (3.2) %, p < 0.0001 at 5 min after administration. The second dose of neostigmine with glycopyrrolate further decreased grip strength mean (SD) ?41 (23) % vs. +1.0 (15) %, p = 0.0004; single twitch height ?25 (15) % vs. ?2.5 (6.6) %, p = 0.0030; predicted forced expiratory volume in 1 s ?23 (24) % vs. ?0.7 (4.4) %, p = 0.0063; and predicted forced vital capacity, ?27.1 (22.0) % vs. ?0.66 (3.9) %, p = 0.0010. Train‐of‐four ratio remained unchanged (p = 0.22). In healthy volunteers, therapeutic doses of neostigmine induced significant and dose‐dependent muscle weakness, demonstrated by a decrease in maximum voluntary hand grip strength and a restrictive spirometry pattern secondary to depolarising neuromuscular blockade.     

Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen

Abstract:  Mycophenolate mofetil (MMF) and sirolimus (SRL) are effective immunosuppressive drugs with distinct safety profile.
Methods:  Kidney transplant recipients receiving tacrolimus (TAC)-based immunosuppressive regimen were randomized to receive fixed daily doses of MMF (2 g/d, n = 50) or SRL (one loading dose of 15 mg, 5 mg/d till day 7 and 2 mg/d thereafter, n = 50) without induction therapy.
Results:  No differences were observed in the incidence of the composite (biopsy-confirmed acute rejection, graft loss or death) end-point (18% vs. 16%, p = 1.000), biopsy confirmed acute rejection (12% vs. 14%, p = 1.000), one-yr patient (94% vs. 98%, p = 0.308), graft (92% vs. 98%, p = 0.168), and death-censored graft survival (98% vs. 100%, p = 0.317) comparing patients receiving MMF or SRL respectively. Patients receiving SRL showed worse safety outcomes, higher mean creatinine (1.6 ± 0.5 mg/dL vs. 1.4 ± 0.3 mg/dL, p = 0.007), higher proportion of patients with proteinuria (52.0% vs. 10.7%, p = 0.041), higher mean urinary protein concentrations (0.3 ± 0.5 g/L vs. 0.1 ± 0.2 g/L, p = 0.012), higher mean cholesterol concentration (217 mg/dL vs. 190 mg/dL, p = 0.030), and higher proportion of patients prematurely discontinued from randomized therapy (26% vs. 8%, p = 0.031).
Conclusion:  In patients receiving TAC, MMF produced similar efficacy but superior safety profile compared with SRL.     

Complement Dependence of Murine Costimulatory Blockade‐Resistant Cellular Cardiac Allograft Rejection

Building on studies showing that ischemia–reperfusion‐(I/R)‐injury is complement dependent, we tested links among complement activation, transplantation‐associated I/R injury, and murine cardiac allograft rejection. We transplanted BALB/c hearts subjected to 8‐h cold ischemic storage (CIS) into cytotoxic T‐lymphocyte associated protein 4 (CTLA4)Ig‐treated wild‐type (WT) or c3^?/? B6 recipients. Whereas allografts subjected to 8‐h CIS rejected in WT recipients with a median survival time (MST) of 37 days, identically treated hearts survived >60 days in c3^?/? mice (p < 0.05, n = 4–6/group). Mechanistic studies showed recipient C3 deficiency prevented induction of intragraft and serum chemokines/cytokines and blunted the priming, expansion, and graft infiltration of interferon‐γ–producing, donor‐reactive T cells. MST of hearts subjected to 8‐h CIS was >60 days in mannose binding lectin (mbl1^?/?mbl2^?/?) recipients and 42 days in factor B (cfb^?/?) recipients (n = 4–6/group, p < 0.05, mbl1^?/?mbl2^?/? vs. cfb^?/?), implicating the MBL (not alternative) pathway. To pharmacologically target MBL‐initiated complement activation, we transplanted BALB/c hearts subjected to 8‐h CIS into CTLA4Ig‐treated WT B6 recipients with or without C1 inhibitor (C1‐INH). Remarkably, peritransplantation administration of C1‐INH prolonged graft survival (MST >60 days, p < 0.05 vs. controls, n = 6) and prevented CI‐induced increases in donor‐reactive, IFNγ‐producing spleen cells (p < 0.05). These new findings link donor I/R injury to T cell–mediated rejection through MBL‐initiated, complement activation and support testing C1‐INH administration to prevent CTLA4Ig‐resistant rejection of deceased donor allografts in human transplant patients.     

The effect of anti‐emetic doses of dexamethasone on postoperative blood glucose levels in non‐diabetic and diabetic patients: a prospective randomised controlled study

There are few data regarding postoperative hyperglycaemia in non‐diabetic compared with diabetic patients following postoperative nausea and vomiting prophylaxis with dexamethasone. Eighty‐five non‐diabetic patients and patients with type‐2 diabetes were randomly allocated to receive intravenous dexamethasone (8 mg) or ondansetron (4 mg). Blood glucose levels were measured at baseline and then 2, 4 and 24 h following induction of anaesthesia. In non‐diabetic patients, the mean (SD) maximum blood glucose was higher in those who received dexamethasone compared with ondansetron (9.1 (2.2) mmol.l^?1 vs. 7.8 (1.4) mmol.l^?1, p = 0.04). In diabetic patients, the mean (SD) maximum blood glucose was also higher in those who received dexamethasone compared with ondansetron (14.0 (2.5) mmol.l^?1 vs. 10.7 (2.4) mmol.l^?1, p < 0.01). Multivariate analysis demonstrated that dexamethasone administration was a significant predictor of maximum postoperative blood glucose increase (p < 0.01) after adjusting for potential confounders. There was no interaction between baseline blood glucose level, or presence or absence of diabetes, and dexamethasone administration. We conclude that dexamethasone increases postoperative blood glucose levels in both non‐diabetics and diabetics.     

如何提高外科危重病人的营养支持疗效

外科危重病人高分解代谢、营养物质需求增加,营养支持是危重病人治疗的重要措施之一。合理、有效的营养支持包括提供合适的营养底物,选择正确的喂养途径和时机。早期肠内营养、改善肠内营养的安全性和耐受性、联合应用肠外肠内营养以满足机体对热量的需求、有效控制高血糖以及提供一些药理营养素均可降低应激状况下机体的分解代谢反应,改善机体重要脏器和免疫功能,降低并发症发生率,缩短入住ICU和住院时间,提高危重病人救治成功率。     

Conversion to sirolimus with calcineurin inhibitor elimination vs. dose minimization and renal outcome in heart and lung transplant recipients

Abstract:  Sirolimus (SRL) has been used as an alternative immunosuppressant strategy to allow either dose minimization or complete withdrawal of calcineurin inhibitors (CNI) therapy to improve renal outcome. One hundred thirty-one heart and 55 lung transplant patients were converted from a CNI to SRL based immunosuppression, with CNI elimination in 25 patients, and dose reduction in 161 patients. Fifty-six (28%) patients died and 65 (33%) patients had a 25% or more decline in estimated glomerular filtration rate (eGFR) during a median follow-up of 18 months. The three groups (SRL only group n = 25; SRL + tacrolimus n = 94; SRL + cyclosporine n = 67) had an initial improvement in estimated glomerular filtration rate (p = 0.05), with subsequent similar slow decline in mean eGFR (repeated measures ANOVA, p = 0.96). After controlling for important potential confounding variables, the three groups had similar renal outcome (p = 0.40) and overall survival (p = 0.45). In conclusion, the benefits of CNI withdrawal vs. minimization as part of SRL-based regimens are similar with regard to renal outcomes and patient survival.     

Calcineurin inhibitor effects on glucose metabolism and endothelial function following renal transplantation

Abstract: Background:  Calcineurin inhibitors (CNI) are involved in the development of post-transplant diabetes mellitus (PTDM). Changes in insulin secretion and sensitivity contribute to the development of PTDM and are associated with endothelial function.
Methods:  In a pre-defined substudy of a previously published randomized trial in renal transplant recipients we compared the effect of CNI treatment (n = 23) with complete CNI-avoidance (n = 21) on insulin secretion and sensitivity (oral glucose tolerance test) as well as endothelial function (laser Doppler flowmetry), 10 wk and 12 months following transplantation.
Results:  Insulin sensitivity differed 10 wk post-transplant and was significantly better after 12 months in patients never treated with CNI drugs [0.091 (0.050) vs. 0.083 (0.036) μmol/kg/min/pmol/L, p = 0.043]. Insulin secretion tended to be higher in CNI treated patients at both time points (p = 0.068). Endothelial function was not significantly different at week 10 [540 (205) vs. 227 (565) arbitary units × minutes, p = 0.35] or month 12 [510 (620) vs. 243 (242), p = 0.33].
Conclusions:  Findings in the present study indicate that long-term CNI treatment negatively affects glucose metabolism and this may contribute to the increased risk for premature cardiovascular disease in CNI treated renal transplant recipients. Further studies to elucidate this hypothesis are, however, needed.     

Optimal interventional treatment and long-term outcomes for biliary stricture after liver transplantation

Abstract:  We undertook an evaluation of the clinical outcomes of endoscopic cholangioplasty (ECP) and percutaneous cholangioplasty (PCP) for biliary strictures after liver transplantation. We compared success rates of intervention, patency after successful intervention and procedure-related morbidities in 79 patients with anastomotic stricture (n = 54) or non-anastomotic stricture (n = 25). Twenty-five ECP and 61 PCP procedures were performed; seven PCP procedures were consecutively performed after failure of ECP. Fifty-one (64.6%) patients were successfully treated by cholangioplasty. Successful intervention rates (60.0% in ECP vs. 59.3% in PCP, p = 1.00) and patencies after successful intervention (44.8 ± 7.4 months in ECP vs. 41.9 ± 3.4 months in PCP, p = 0.47) were no different for the two techniques. However, the number of intervention sessions for PCP (7.2 ± 0.6) was higher than for ECP (2.9 ± 0.6) (p < 0.01). Multivariate analysis showed that only an anastomotic stricture was found to be related with a longer patency with an estimated odds ratio of 5.74 (p = 0.04) and had a tendency to be associated with successful intervention with an estimated odds ratio of 3.12 (p = 0.07) irrespective of techniques. Endoscopic access should be the preferred first approach in patients with biliary stricture after liver transplantation irrespective of the type of stricture, in view of its less invasive nature and patient convenience.     

Impact of tacrolimus and mycophenolate mofetil regimen vs. a conventional therapy with steroids on cardiovascular risk in liver transplant patients

The aim of this study was to evaluate the impact of a steroid‐free regimen with tacrolimus and mycophenolate mofetil (modified therapy) vs. a standard regimen of tacrolimus and steroids on the cardiovascular risk score of liver transplant recipients. Patients who received a liver transplant were randomized to a modified therapy (n = 58) or a standard regimen (n = 59). Both groups were balanced at baseline, except for a higher prevalence of diabetes mellitus (DM) (p < 0.01) and a higher serum creatinine concentration (p < 0.05) in the modified therapy group. After 12 months, the prevalence of new‐onset DM, arterial hypertension, hypercholesterolemia, hypertriglyceridemia, and changes in cardiovascular risk factors was similar in both groups. The increase in serum creatinine (mg/dL) compared to baseline at one yr post‐transplantation was numerically lower in the modified therapy group (0.22 ± 0.42) than in the standard regimen group (0.41 ± 0.67) (p = 0.068). Although estimated cardiovascular risk score did not vary significantly compared to baseline in either group, there was a slight reduction in the modified regimen (?0.27 ± 2.87) vs. a mild increase (0.17 ± 2.94) in the standard regimen (p = 0.566). In conclusion, a steroid‐free regimen with tacrolimus and mycophenolate mofetil was associated with a trend toward better preservation of kidney function and reduction of cardiovascular risk score.     

Use of remifentanil as a sedative agent in critically ill adult patients: a meta-analysis

This meta-analysis examined the benefits of using remifentanil as a sedative agent in critically ill patients. A total of 11 randomised controlled trials, comparing remifentanil with another opioid or hypnotic agent in 1067 critically ill adult patients, were identified from the Cochrane controlled trials register and EMBASE and MEDLINE databases, and subjected to meta-analysis. Remifentanil was associated with a reduction in the time to tracheal extubation after cessation of sedation (weighted-mean-difference −2.04 h (95% CI −0.39 to −3.69 h); p = 0.02). Remifentanil was, however, not associated with a significant reduction in mortality (relative risk 1.01 (95% CI 0.67–1.52); p = 0.96), duration of mechanical ventilation, length of intensive care unit stay, and risk of agitation (relative risk 1.08 (95% CI 0.64–1.82); p = 0.77) when compared to an alternative sedative or analgesic agent. The current evidence does not support the routine use of remifentanil as a sedative agent in critically ill adult patients.     

Influence of liver-disease etiology on long-term quality of life and employment after liver transplantation

The etiology of liver disease would expectedly affect health‐related quality of life (HRQoL) and employment after liver transplantation (LT), but studies are scarce. We sent the 15D HRQoL instrument and an employment questionnaire to all 401 adult LT patients alive in Finland in 2007. The response rate was 89% (n = 353; mean of eight yr since LT). In age‐adjusted analysis, patients transplanted for primary sclerosing cholangitis (PSC; n = 56), primary biliary cirrhosis (PBC; n = 72), acute liver failure (ALF; n = 76), alcoholic cirrhosis (n = 38), or liver tumor (n = 22) exhibited comparable HRQoL, whereas the combined group of miscellaneous chronic liver diseases (n = 89) exhibited significantly higher HRQoL scores (p = 0.003). Among working‐aged patients (20–65 yr at LT), employment rates were highest in the PSC (56%) group and lowest in the ALF (39%) and PBC (29%) groups. In age‐adjusted logistic regression, patients with PSC or alcoholic cirrhotics were 2.4‐ and 2.5‐fold more likely to resume work after LT than patients with PBC. In conclusion, HRQoL scores late after LT were in general relatively high and comparable among disease groups. Patients with PSC or alcoholic cirrhosis were most likely to resume work after LT. The relatively low employment among patients with ALF may merit enhanced rehabilitation efforts.     

Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials

We conducted a systematic review of the effects of dexmedetomidine on cardiac outcomes following non-cardiac surgery. We included prospective, randomised peri-operative studies of dexmedetomidine that reported mortality, cardiac morbidity or adverse drug events. A PubMed Central and EMBASE search was conducted up to July 2007. The reference lists of identified papers were examined for further trials. Of 425 studies identified, 20 were included in the meta-analysis (840 patients). Dexmedetomidine was associated with a trend towards improved cardiac outcomes; all-cause mortality (OR 0.27, 95% CI 0.01–7.13, p = 0.44), non-fatal myocardial infarction (OR 0.26, 95% CI 0.04–1.60, p = 0.14), and myocardial ischaemia (OR 0.65, 95% CI 0.26–1.63, p = 0.36). Peri-operative hypotension (26%, OR 3.80, 95% CI 1.91–7.54, p = 0.0001) and bradycardia (17%, OR 5.45, 95% CI 2.98–9.95, p < 0.00001) were significantly increased. An anticholinergic did not reduce the incidence of bradycardia (p  =  0.43). A randomised placebo-controlled trial of dexmedetomidine is warranted.     

What happens to the kidney in an SPK transplant when the pancreas fails due to a technical complication?

Abstract:  We examined a group of SPK recipients that had early (<90 d post-transplant) pancreas graft failure caused by a technical complication, and looked at outcomes of the kidney graft in these recipients. Of 289 SPK transplants, 36 (12.5%) had early pancreas graft failure because of a technical complication: thrombosis (n = 16), leak (n = 5), infection (n = 14), and pancreatitis (n = 1). Once the pancreas was lost, there was a high incidence of subsequent kidney graft failure. Kidney graft survival in these 36 recipients was 71.4% at one yr and 59.5% at three yr, significantly inferior compared to recipients that did not have early failure of the pancreas (86% at one yr and 82% at three yr, p < 0.001). Of the 36 recipients with early pancreas loss, 18 have gone on to failure of the kidney graft. Causes included thrombosis (n = 3), infection (n = 1), death with function (n = 6), chronic rejection (n = 4), ischemia (n = 1), and other (n = 3). Of the 18 kidney graft failures, nine occurred within three months after loss of the pancreas graft, usually either because of graft thrombosis, or patient death (usually from systemic sepsis). Multivariate analysis showed technical failure of the pancreas to be the most significant risk factor for kidney graft loss (HR = 2.08, p = 0.006).     

The added value of cardiac index and pulse pressure variation monitoring to mean arterial pressure‐guided volume therapy in moderate‐risk abdominal surgery (COGUIDE): a pragmatic multicentre randomised controlled trial

There is disagreement regarding the benefits of goal‐directed therapy in moderate‐risk abdominal surgery. Therefore, we tested the hypothesis that the addition of non‐invasive cardiac index and pulse pressure variation monitoring to mean arterial pressure‐based goal‐directed therapy would reduce the incidence of postoperative complications in patients having moderate‐risk abdominal surgery. In this pragmatic multicentre randomised controlled trial, we randomly allocated 244 patients by envelope drawing in a 1:1 fashion, stratified per centre. All patients had mean arterial pressure, cardiac index and pulse pressure variation measured continuously. In one group, healthcare professionals were blinded to cardiac index and pulse pressure variation values and were asked to guide haemodynamic therapy only based on mean arterial pressure (control group). In the second group, cardiac index and pulse pressure variation values were displayed and kept within target ranges following a pre‐defined algorithm (CI ‐PPV group). The primary endpoint was the incidence of postoperative complications within 30 days. One hundred and seventy‐five patients were eligible for final analysis. Overall complication rates were similar (42/94 (44.7%) vs. 38/81 (46.9%) in the control and CI ‐PPV groups, respectively; p = 0.95). The CI ‐PPV group had lower mean (SD ) pulse pressure variation values (9.5 (2.0)% vs. 11.9 (4.6)%; p = 0.003) and higher mean (SD ) cardiac indices (2.76 (0.62) l min^?1.m^?2 vs. 2.53 (0.66) l min^?1.m^?2; p = 0.004) than the control group. In moderate‐risk abdominal surgery, we observed no additional value of cardiac index and pulse pressure variation‐guided haemodynamic therapy to mean arterial pressure‐guided volume therapy with regard to postoperative complications.     

004Topical Zinc Oxide for Open Pilonidal Wounds

Extended healing time and lack of documented effective treatments of sacrococcygeal pilonidal disease create substantial problems. Locally applied zinc oxide has been reported to promote wound healing. We have compared topical zinc oxide (3%) with placebo meshes for pilonidal wounds healing by secondary intention in a randomized, double‐blind, placebo‐controlled multicenter trial. Sixty‐four consecutive patients, 53 males, aged between 18 and 60 years (median 26 years) with excised pilonidal wounds were centrally randomized to local zinc oxide (30 mg/g, n = 33) or to placebo (n = 31) mesh treatment. Patients were followed with strict recording of beneficial and harmful effects. The median healing times were 54 days (42–71 days, interquartile range, n = 33) for the zinc group and 62 days (55–82 days, n = 31) for the placebo group. This difference was not statistically different (p = 0.32). Based on Cox regression analysis initial wound volume influenced healing negatively (p = 0.016) while smoking (p = 0.011) was associated with faster wound healing. Significantly (p < 0.01) more placebo (n = 12) than zinc oxide‐treated patients (n = 3) needed antibiotics postoperatively. Although topical zinc oxide increased (p < 0.001) wound fluid zinc levels (1830 ± 405 μM, mean ± SEM) compared with placebo (3.1 ± 1.6 μM) serum‐zinc levels did not differ significantly between the zinc (13.5 ± 0.4 μM) and placebo (12.8 ± 0.4 μm) groups on postoperative day 7. No adverse events were recorded. Topical zinc oxide treatment did not accelerate time to closure of open pilonidal wounds but was associated with reduced antibiotic usage.     

The influence of CTLA‐4 single nucleotide polymorphisms on acute kidney allograft rejection in Turkish patients

Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) is a cell surface protein, which down‐regulates the immune response at CTLA‐4/CD28/B7 pathway. We aimed to investigate the influence of the ?318C/T, +49A/G, ?1661A/G and CT60A/G, and CTLA‐4 gene polymorphisms on acute rejection of kidney allograft in Turkish patients. The study design was a case–control study that consists of three groups: Group 1 (n = 34) represented the kidney transplant (Ktx) recipients who experienced acute rejection, Group 2 (n = 47) was randomly assigned Ktx recipients without acute rejection, and Group 3 (n = 50) consisting of healthy volunteers to evaluate the normal genomic distribution. The polymerase chain reaction–restriction fragment length polymorphism technique was used to determine the polymorphisms. Genotype and allele frequencies among three groups denoted similar distributions for +49A/G, ?1661A/G, and CT60A/G. Conversely, ?318C/T genotype was three times more frequent in the acute rejection group than in the non‐rejection group (OR = 3.45; 95%CI = 1.18–10.1, p = 0.015) and two times more frequent than the healthy control group (OR = 2.45; 95% CI = 0.98 – 6.11, p = 0.047). Additionally, having a T allele at ?318 position was significantly associated with acute rejection (0.147 vs. 0.043, OR = 3.45; 95% CI = 1.13–10.56, p = 0.02). 318C/T gene polymorphism and T allelic variant were found to be associated with increased acute rejection risk in Turkish kidney allograft recipients.     

Dynamics of anti‐human leukocyte antigen antibodies after renal transplantation and their impact on graft outcome

The purpose of this study was to sequentially monitor anti‐HLA antibodies and correlate the results with antibody‐mediated rejection (AMR), graft survival (GS), and graft function (GF). We collected sera from 111 kidney transplant recipients on transplant days 0, 7, 14, 30, 60, 90, 180, and 360 and analyzed PRA levels by ELISA. DSAs were analyzed by single‐antigen beads in rejecting kidneys. At pre‐transplant, 79.3% of the patients were non‐sensitized (PRA = 0%) and 20.7% were sensitized (PRA > 1%). After transplant, patients were grouped by PRA profile: no anti‐HLA antibodies pre‐ or post‐transplant (group HLApre?/post?; n = 80); de novo anti‐HLA antibodies post‐transplant (group HLApre?/post+; n = 8); sensitized pre‐transplant/increased PRA post‐transplant (group HLApre+/post↑; n = 9); and sensitized pre‐transplant/decreased PRA post‐transplant (group HLApre+/post↓; n = 14). De novo anti‐HLA antibodies were detected at 7–180 d. In sensitized patients, PRA levels changed within the first 30 d post‐transplant. Incidence of AMR was higher in HLApre?/post+ and HLApre+/post↑ than in HLApre?/post?, and HLApre+/post↓ (p < 0.001) groups. One‐yr death‐censored GS was 36% in group HLApre+/post↑, compared with 98%, 88% and 100% in groups HLApre?/post?, HLApre?/post+, and HLApre+/post↓, respectively (p < 0.001). Excluding first‐year graft losses, GF and GS were similar among the groups. In conclusion, post‐transplant antibody monitoring can identify recipients at higher risk of AMR.     

Kidney transplant ureteroneocystostomy: comparison of full-thickness vs. Lich-Gregoir techniques

Despite a variety of urinary tract reconstructive techniques, urinary complications are the most frequent technical adverse event following kidney transplantation. We examined outcomes of two ureteroneocystostomy techniques, the full‐thickness (FT) technique and the Lich–Gregoir (LG) technique in 634 consecutive kidney‐alone transplants (327 FT and 307 LG) between December 2006 and December 2010. Urological complications at one yr post‐transplantation occurred in 27 cases (4.3%) including 16 ureteral strictures (2.5%), four ureteral obstructions (0.6%) owing to donor‐derived stones or intrinsic hematoma, and seven urine leaks (1.1%). Compared with LG, the FT technique was associated with similar proportions of ureteral complications overall (3.9% vs. 4.6%, p = 0.70), ureteral strictures (3.7% vs. 1.3%, p = 0.08), urinary stones/hematoma (1.0% vs. 0.3%, p = 0.36), and overall urinary leaks (1.6% vs. 0.6%, p = 0.22); however, the FT technique was associated with somewhat fewer urine leaks at the ureterovesical junction (0% vs. 1.3%, p = 0.05). There were no differences between the two groups in terms of length of stay, delayed graft function, urinary tract infection with the first post‐transplant year, estimated glomerular filtration rate, and overall graft and patient survival. The FT technique of ureteroneocystostomy is technically simple to perform and has a similar incidence of urinary complications compared with the LG technique.