Steroid withdrawal in renal transplant patients on triple therapy with a calcineurin inhibitor and mycophenolate mofetil: a meta-analysis of randomized, controlled trials

BACKGROUND: Two previous meta-analyses of randomized, controlled trials of steroid withdrawal after renal transplantation have shown significant increases in acute rejection (both analyses) and graft failure rates (the last analysis). A new examination of this topic including only randomized, controlled trials based on currently used, new, potent therapy with calcineurin inhibitors and mycophenolate mofetil (MMF), avoiding early trials with azathioprine, is justified. METHODS: Steroid withdrawal in patients on triple therapy including a calcineurin inhibitor and MMF was assessed through meta-analysis of randomized, controlled trials in which intention-to-treat rates of acute rejection and renal allograft failure were established after steroid withdrawal or continuation. RESULTS: Six trials were included, four in patients receiving cyclosporine and two in patients receiving tacrolimus. The risk ratio (RR) for acute rejection was 2.28 (95% confidence interval [CI], 1.65-3.16; P < 0.00001) and the pooled risk difference (RD) was 0.08 (95% CI, 0.05-0.11; P < 0.001), indicating that the proportion of patients with acute rejection after prednisone withdrawal was significantly higher compared with controls. The RR for graft failure was 0.73 (95% CI, 0.42-1.28; P = 0.27) and the RD was -0.01 (95% CI, -0.03-0.01; P = 0.28), indicating that the proportion of patients with graft failure after withdrawal was not significantly different from that observed in controls. Total cholesterol was significantly lower after steroid withdrawal (weighted mean difference, -0.53 microM (95% CI, -0.70 to -0.36; P < 0.0001). CONCLUSIONS: Renal allograft recipients on triple therapy with a calcineurin inhibitor, MMF, and steroids are at low but significant risk of acute rejection after steroid withdrawal but do not suffer an increased risk of early graft failure. It is necessary to extend controlled follow-up to confirm graft function stabilization.     

Calcineurin Inhibitor Avoidance and Withdrawal for Kidney Transplantation: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Objective

Many studies have compared the safety and efficacy of the calcineurin inhibitor (CNI) avoidance or CNI withdrawal regimens with typical CNI regimens, but the results remain controversial. The aim of this systematic review and meta-analysis is to make a profound review and an objective appraisal of the safety and efficacy of the CNI avoidance and CNI withdrawal protocols.

Methods

We searched PUBMED, EMBASE, and the reference lists of retrieved studies to identify randomized controlled trials (RCTs) that referred to CNI-free regimens, CNI avoidance, or CNI withdrawal for kidney transplantation. Eight publications involving 27 different RCTs and a total of 3953 patients were used in the analysis.

Results

Use of mammalian target of rapamycin inhibitors, namely sirolimus (SRL), in combination with mycophenolate, conserve graft function at 1 year (glomerular filtration rage [GFR]: mean difference MD 6.21, 95% CI 0.02–12.41, P = .05; serum creatinine: MD −0.11, 95% CI −0.19 to −0.03, P = .01, respectively) and 2 years post-transplant (GFR: MD 13.96, 95% CI 7.32–20.60, P < .0001). Similarly, early withdrawal (≤6 months) of CNIs protect graft function at 1 year after transplant (GFR: MD 7.03, 95% CI 4.84–9.23, P < .00001, serum creatinine: MD −0.21, 95% CI −0.22 to −0.19, P < .00001, respectively). CNI avoidance and withdrawal strategies are associated with higher incidence of acute rejection at 1 year post-transplant (odds ratio OR 1.74, 95% CI 1.08–2.81, P = .02; OR 1.78, 95% CI 1.35–2.34, P < .0001, respectively). At 2 years after transplant, there was no significant difference (OR 0.92, 95% CI 0.33–2.51, P = .86; OR 2.42, 95% CI 1.01–5.82, P = .05, respectively). Meanwhile, neither adverse events nor patient/graft survival differed significantly between the CNI-free and CNI protocols at 1 and 2 years. Referring to long-term results in the published RCTs, use of CNI-free and CNI withdrawal regimens achieve better renal function vs CNI regimens, with no significant difference in patient and graft survival, acute rejection, and most reported adverse events.

Conclusions

In conclusion, this systematic review and meta-analysis suggests that renal recipients with early withdrawal of CNI drugs or avoiding CNI with SRL perform better to conserve graft function at 1 and 2 years post-transplant. Though the use of CNI regimens performs no better in 2-year acute rejection vs the contrast group, they greatly decrease the incidence of acute rejection at the first year after transplantation. CNI avoidance and withdrawal regimens improve the long-term renal function and perform similarly in the acute rejection, patient and graft survival, and adverse events. Due to the limited amounts of long-term studies, more high-quality RCTs are needed.     

Effects of the Intensity of Immunosuppressive Therapy on Outcome of Treatment for CMV Disease in Organ Transplant Recipients

An effective host immune response, critical for successful control of Cytomegalovirus (CMV) disease in solid organ transplant recipients, is affected by intensity and type of immunosuppressive therapy. We used information prospectively captured in the VICTOR‐trial to investigate the impact of immunosuppressive therapy on short‐ and long‐term outcomes of CMV treatment in organ transplant recipients. Dual, as compared to triple, immunosuppressive therapy ([odds ratios] OR of 2.55; 95% CI: 1.51–4.60; p = 0.002), lower blood concentrations of calcineurin inhibitors (OR of 5.53; CI: 1.04–29.35; p = 0.045), and longer time since transplantation (OR of 1.70; CI: 1.01–2.87; p = 0.047) all showed better early (Day 21) CMV DNAemia eradication. We observed no effect of the intensity of the immunosuppressive therapy on overall rates of viral eradication or recurrence. The type of calcineurin inhibitor (tacrolimus/cyclosporine) or use of mycophenolate did not affect treatment efficacy, although both tacrolimus and mycophenolate treated patients showed a lower rate of virological recurrence OR 0.51 (95% CI: 0.26–0.98; p = 0.044) and OR 0.45 (95% CI: 0.22–0.93; p = 0.031), respectively. Lower total intensity of immunosuppressive therapy was associated with more effective early, but not overall, CMV DNAemia eradication by valganciclovir/ganciclovir therapy. Both mycophenolate and tacrolimus (rather than cyclosporine) therapy seem to be associated with reduced risk of recurrence.     

Risk factors for capillary C4d deposition in kidney allografts: evaluation of a large study cohort

BACKGROUND: Capillary deposition of the complement split product C4d has turned out to be a valuable marker of antibody-mediated rejection. The impact of pre- and posttransplant variables including particular immunosuppressive regimens on the frequency of C4d deposition has not yet been systematically investigated in a large multivariate analysis. METHODS: In this retrospective study, the authors evaluated the incidence of C4d deposition in 388 kidney transplant recipients subjected to diagnostic biopsy within the first 6 months and analyzed the influence of potential confounders on the rate of C4d-positive graft dysfunction by applying multivariate logistic regression. RESULTS: Sixty-six recipients (17%) developed linear C4d deposits in at least a quarter of peritubular capillaries, a finding associated with inferior 1-year allograft survival (73% vs. 88% in C4d-negative patients, P=0.0003). A 50% reduction in the odds of C4d-positive graft dysfunction was found if calcineurin inhibitor or mycophenolate mofetil (MMF) therapy was started 2 to 4 hr before transplantation when compared with initiation after surgery (adjusted odds ratio [OR], 0.5; P=0.03). No differences with respect to C4d staining results were found for the use of tacrolimus, MMF, or sirolimus, or for cyclosporine C2 monitoring. Retransplantation (OR, 3.6; P<0.001) and presensitization (OR, 3.1; P=0.002) turned out to be strong independent risk factors for C4d deposition. CONCLUSIONS: The authors' results suggest a reduced risk of C4d-positive graft dysfunction for patients receiving immunosuppression before transplantation. Apart from first dose timing, no influence of particular immunosuppressive strategies on C4d staining results was found.     

Posttransplantation anemia at 12 months in kidney recipients treated with mycophenolate mofetil: risk factors and implications for mortality

Although posttransplantation anemia (PTA) is common in the mycophenolate mofetil era, its impact on patient survival is unknown. This retrospective cohort study characterized factors that are associated with PTA 12 mo after transplantation in mycophenolate mofetil-treated kidney recipients and explored whether 12-mo PTA affects outcomes. The records of 626 kidney recipients were examined for presence of anemia (hemoglobin <12 g/dl). Multivariate regression models, fit with covariates that had unadjusted relationships, investigated both risk factors for 12-mo PTA and whether 12-mo PTA contributes to mortality. Anemia prevalence was 72, 40, and 20.3% at 1, 3, and 12 mo, respectively. By multivariate logistic regression, anemia at 3 mo (odds ratio [OR] 10.0; 95% confidence interval [CI] 5.3 to 17.1; P = 0.0001), donor age (OR 1.0; 95% CI 1.1 to 1.3; P = 0.005), and 3-mo creatinine (OR 2.0; 95% CI 1.2 to 3.3; P = 0.044) were associated with 12-mo PTA. The PTA cohort had inferior patient survival (P = 0.02, log rank) and a higher proportion of cardiovascular deaths (6.3 versus 2.2%; P = 0.017) than nonanemic patients. By Cox regression, 12-mo PTA (hazard ratio [HR] 3.0; 95% CI 1.3 to 6.7; P = 0.009), 12-mo creatinine (HR 1.3; 95% CI 1.1 to 1.4; P = 0.008), age at transplantation (HR 1.1; 95% CI 1.1 to 1.2; P = 0.004), and hepatitis C seropositivity (HR 2.8; 95% CI 1.1 to 7.0; P = 0.03) were associated with mortality. There was no interaction between 12-mo PTA and serum creatinine. In conclusion, 12-mo PTA is associated with an increased risk for patient death. The presence of anemia 3 mo after kidney transplantation is a major determinant of 12-mo PTA. PTA in kidney recipients therefore should be defined by its persistence or occurrence beyond the third posttransplantation month.     

Association of hepatitis C with posttransplant diabetes in renal transplant patients on tacrolimus

Posttransplant diabetes mellitus (PTDM) remains a common complication of immunosuppression. Although multiple risk factors have been implicated, none have been clearly identified as predisposing to the increased PTDM frequency observed in patients on tacrolimus. Hepatitis C virus (HCV) has been associated with diabetes and is a significant renal transplant comorbidity. In this study, records of 427 kidney recipients who had no known diabetes before transplantation were retrospectively examined. A multivariate logistic regression model was fit with covariates that had unadjusted relationships with PTDM to examine the independent relationship of HCV and the odds of development of PTDM by 12 mo posttransplant. A potential interaction between HCV and the use of tacrolimus as maintenance therapy on the odds of the development of PTDM was examined. Overall, PTDM occurred more frequently in HCV(+) than HCV(-) patients (39.4% versus 9.8%; P = 0.0005). By multivariate logistic regression, HCV (adjusted odds ratio [OR], 5.58; 95% confidence interval [CI], 2.63 to 11.83; P = 0.0001), weight at transplantation (adjusted OR 1.028; 95% CI, 1.00 to 1.05; P = 0.001), and tacrolimus (adjusted OR, 2.85; 95% CI, 1.01 to 5.28; P = 0.047) were associated with PTDM. A significant interaction (P = 0.0001) was detected between HCV status and tacrolimus use for the odds of PTDM. Among the HCV(+) cohort, PTDM occurred more often in tacrolimus-treated than cyclosporine A-treated patients (57.8% versus 7.7%; P < 0.0001). PTDM rates in HCV(-) patients were similar between the two calcineurin inhibitors (10.0% versus 9.4%; P = 0.521, tacrolimus versus cyclosporine A). In conclusion, HCV is strongly associated with PTDM in renal transplant recipients and appears to account for the increased diabetogenicity observed with tacrolimus.     

Do wound complications or lymphoceles occur more often in solid organ transplant recipients on mTOR inhibitors? A systematic review of randomized controlled trials

mTOR inhibitors have been associated with wound complications and lymphoceles. We systematically reviewed randomized controlled trials (RCTs) to compare these outcomes for solid organ transplant recipients. Relevant medical databases were searched to identify RCTs in solid organ transplantation comparing mTOR inhibitors with an alternative therapy reporting on wound complications and/or lymphoceles. Methodological quality of RCTs was assessed. Pooled analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Thirty-seven RCTs in kidney, heart, simultaneous pancreas-kidney and liver transplantation were included. Pooled analyses showed a higher incidence of wound complications (OR 1.77, CI 1.31-2.37) and lymphoceles (OR 2.07, CI 1.62-2.65) for kidney transplant recipients on mTOR inhibitors together with calcineurin inhibitors (CNIs). There was also a higher incidence of wound complications (OR 3.00, CI 1.61-5.59) and lymphoceles (OR 2.13, CI 1.57-2.90) for kidney transplant recipients on mTOR inhibitors together with antimetabolites. Heart transplant patients receiving mTOR inhibitors together with CNIs also reported more wound complications (OR 1.82, CI 1.15-2.87). We found a higher incidence of wound complications and lymphoceles after kidney transplantation and a higher incidence of wound complications after heart transplantation for immunosuppressive regimens that included mTOR inhibitors from the time of transplantation.     

Mycophenolate mofetil versus azathioprine for prevention of chronic allograft dysfunction in renal transplantation: the MYSS follow-up randomized, controlled clinical trial

The Mycophenolate Steroids Sparing (MYSS) study found that in renal transplant recipients who were on immunosuppressive therapy with the cyclosporine microemulsion Neoral, mycophenolate mofetil (MMF) was not better than azathioprine in preventing acute rejection at 21 mo after transplantation and was 15 times more expensive. The MYSS Follow-up Study, an extension of MYSS, was aimed at comparing long-term outcome of 248 MYSS patients according to their original randomization to MMF (1 g twice daily) or azathioprine (75 to 100 mg/d). Primary outcome was estimated GFR at 5 yr after transplantation. Mean 5-yr GFR difference between azathioprine and mycophenolate was 4.67 ml/min per 1.73 m(2) (95% confidence interval [CI] -0.43 to 9.77 ml/min per 1.73 m(2); P = 0.07). GFR from month 6 (mean +/- SEM: 54.3 +/- 1.6 versus 53.9 +/- 1.5 ml/min per 1.73 m(2); P = 0.83) to month 72 after transplantation (49.5 +/- 2.2 versus 47.3 +/- 2.4 ml/min per 1.73 m(2); P = 0.50); GFR slopes (mean +/- SEM: -1.10 +/- 0.56 versus -1.23 +/- 0.31 ml/min per 1.73 m(2) per year; P = 0.83); and 72-mo patient mortality (4.0 versus 4.0% [P = 0.95]; HR 0.96; 95% CI 0.28 to 3.31; P = 0.95), graft loss (6.8 versus 6.1% [P = 0.82]; HR 0.89; 95% CI 0.32 to 2.46; P = 0.83), incidence of persistent proteinuria (25.0 versus 27.4%; P = 0.72), late (>6 mo after transplantation) rejections (25.3 versus 21.2%; P = 0.53), and adverse events were similar on azathioprine (n = 124) and MMF (n = 124), respectively. Outcomes in the two groups were comparable also among patients with or without steroid therapy, considered separately. In kidney transplantation, the long-term risk/benefit profile of MMF and azathioprine therapy in combination with cyclosporine Neoral is similar. In view of the cost, standard immunosuppression regimens for kidney transplantation should perhaps include azathioprine rather than MMF.     

Characteristics of potential living kidney donors in Ivory Coast: a survey prior to a project of kidney transplantation in French Black Africa

The source of living kidney donors in the general population remains underused. The present study aims at assessing the prevalence and the characteristics of potential living kidney donors in Ivory Coast in a view of a project of kidney transplantation in French Black Africa. A survey was undertaken in Abidjan from 30 June to 7 July 2006. Nine hundred (and) sixty-two subjects living in the capital and aged between 19 and 64 years old were randomly chosen using data from the 1998 population census. Subjects were asked their age, gender, nationality, marital status, information on kidney graft and renal failure, and their willingness to donate kidney to a relative or friend for transplantation purpose. Seventy per cent of the population study appeared favourable to kidney donation. Potentials living kidney donors have displayed following characteristics: age inferior to 26 years old [OR=2.08, P<0.02, 95%CI: 1.10-3.92]; Ivorians national [OR=2.72, P<0.002, 95% CI 1.42-5.21]; having heard of kidney transplantation (OR=1.89, P<0.047, 95% CI 1-3.54]); the death of a relative or friend from renal failure [OR=1.82, P<0.002, 95% CI 1.25 2.67]. Being married adversely affect kidney donation [OR=0.52, P<0.0002, 95% CI 0.34-0.79]. Potentials living kidney donors are in great number in Ivory Coast, who had specific characteristics.     

New immunosuppressive therapies and surgical complications after renal transplantation

Background

To analyze the association between the principal immunosuppressive drugs (mycophenolate mofetil, calcineurin inhibitors and mammalian target of rapamycin [mTOR] inhibitors) used in the routine management of kidney transplant patients and the development of postoperative surgical complications.

Materials and Methods

We analyzed 415 kidney transplants, studying the influence of various immunosuppressive regimens on the main postoperative surgical complications.

Results

The mean follow-up for the entire group was 72.8 months (± 54.2 SD). Patients treated with myeophonolate mofetil (MMF) and cyclosporine (n = 121) experienced a higher frequency of wound eventration odds ratio [OR], 5.2; 95% confidence interval [CI], 1.2-23.5; P = .03) compared with azathioprine and cyclosporine (n = 71). Compared with transplant recipients treated with tacrolimus and MMF (n = 181), transplant recipients treated with cyclosporine and MMF (n = 121) had a significantly greater frequency of wound eventration (OR, 3.7; 95% CI, 1.5-9.5; P = .005), urologic (OR, 2; 95% CI; 1.02-3.9; P = .04), wound (OR; 2.2; 95% CI; 1.07-4.6; P = .03), late (OR, 1.7; 95% CI; 1.01-3.03; P = .04), and Clavien grade 3 surgical complications (OR; 1.9; 95% CI, 1.1-3.37; P = .01). Patients treated with mTOR inhibitors (n = 26) had higher rates of lymphocele (OR, 3.6; 95% CI, (1.1-11.4; P = .002) compared with those who received tacrolimus (n = 197).

Conclusions

New immunosuppressive drugs have improved short-term functional results; however, in some cases they seem to increase surgical complications rates.     

Cytokine gene polymorphisms and risks of acute rejection and delayed graft function after kidney transplantation

BACKGROUND: Pretransplantation identification of patients at an increased risk for adverse events would allow more individualized treatment strategies possibly improving long-term outcome. We studied cytokine gene polymorphisms of kidney allograft recipients and their donors to identify factors predisposing for acute rejection (AR) and delayed graft function (DGF). METHODS: A total of 291 adult cadaver kidney recipients transplanted at a single transplantation centre between 1999 and 2002 were investigated. Recipients and donors were typed for TNF-alpha(-308G/A), TGF-beta1(codon 10T/C, codon 25C/G), IL-10(-1082G/A, -819C/T, -592C/A), IL-6(-174C/G), and IFN-gamma(+874T/A) polymorphisms using a SSP-PCR kit. An AR episode was defined based on clinical and histological findings (Banff criteria). RESULTS.: The incidence of AR was 17%. In univariate statistical analyses recipients with TNF-alpha -308AA-genotype were found to be at a significantly increased risk for rejection (odds ratio [OR] 5.0, 95% CI 3.0-8.3, P = 0.003). The association was independent from the patient-donor HLA-mismatch status. In addition, patients with IL-10 ACCACC, ATAATA, GCCATA (-1082A/G, -819C/T, -592C/A, respectively) haplotypes were predisposed to rejection (OR 1.9, 95% CI 1.1-3.1, P = 0.016). Further, the combination of recipient TGF-beta1 25GG-genotype and donor IL-10 -819T-allele was associated with rejection (OR 1.8, 95% CI 1.1-3.0, P = 0.027). These variables remained significant risk factors also in a multivariate logistic regression analysis. The incidence of DGF was 22%. The risk was increased by a donor TNF-alpha -308GA-genotype (OR 1.6, 95% CI 1.1-2.6, P = 0.040). CONCLUSIONS: Our results confirm that cytokine gene polymorphisms influence the outcome of kidney transplantation. Our data especially identify the TNF-alpha -308AA-genotype as a factor predisposing for AR episodes.     

HLA mismatches remain risk factors for acute kidney allograft rejection in patients receiving quadruple immunosuppression with anti-interleukin-2 receptor antibodies

BACKGROUND: New immunosuppressive drugs such as anti-interleukin-2 receptor antibodies (aIL2R) and mycophenolate mofetil (MMF) have reduced the incidence of acute rejection after renal transplantation. Whether matching donor and recipient human leukocyte antigen (HLA) antigens is still relevant in patients receiving modern immunosuppression has been questioned. METHODS: We retrospectively analyzed the incidence and risk factors of acute rejection during the first posttransplant year and the impact of acute rejection on long-term graft survival in a cohort of 208 renal transplant patients treated with aIL2R (basiliximab, n=166; daclizumab, n=42), calcineurin inhibitors (tacrolimus, n=180; cyclosporin, n=28), mycophenolate mofetil, and steroids. Graft and patient survival were calculated by the Kaplan-Meier method. Risk factors for acute rejection were analyzed by logistic regression modeling. RESULTS: Twenty-seven patients were treated for acute rejection (26 biopsy-proven) during the first posttransplant year. The Kaplan-Meier estimate of first-year acute rejection was 13.2%. The number of HLA mismatches (odds ratio [OR] 1.65 per HLA mismatch) and long periods of dialysis before transplantation (OR 3.1 for more than 4 years of dialysis) were the only independent risk factors for first-year acute rejection. First-year acute rejection was associated with a significant reduction in overall and death-censored graft survival at 5 years after transplantation. CONCLUSIONS: Although infrequent in patients receiving modern immunosuppressive drugs, acute rejection remains an important risk factor for graft loss after renal transplantation. Our results suggest that better HLA matching and shorter periods of dialysis before transplantation could reduce acute rejection rates and further improve outcomes under current immunosuppressive regimens.     

Patients undergoing infrainguinal bypass to treat atherosclerotic vascular disease are underprescribed cardioprotective medications: effect on graft patency, limb salvage, and mortality

INTRODUCTION: Established American Heart Association guidelines recommend the use of statin drugs, angiotensin converting enzyme (ACE) inhibitors, and antiplatelet agents in patients with systemic atherosclerosis, such as those undergoing operative intervention to treat peripheral atherosclerotic disease. Many of these patients have not received treatment of coronary heart disease and have not been prescribed these medications. Whether statin drugs and ACE inhibitors confer an improvement in graft patency, limb salvage, and operative mortality is unknown. METHODS: Consecutive patients who underwent infrainguinal bypass between 1997 and 2002 were evaluated for demographic data, comorbid disease, medication use, as well as cumulative graft patency, limb salvage, and mortality. Univariate, multivariate logistical regression, and Kaplan-Meier analyses were performed. P <.05 was considered significant. RESULTS: Two hundred ninety-three patients (mean age, 64 years; 67% men) underwent 338 infrainguinal bypass procedures with autologous vein (n = 218), prosthetic grafts (n = 88), or composite prosthetic-vein grafts (n = 32). Limb salvage was the operative indication in 75% of procedures. Coexisting diseases included hypertension (70%), diabetes (52%), hyperlipidemia (37%), coronary heart disease (51%), congestive heart failure (14%), and active tobacco use (30%). Statin drugs were taken by 56% of patients, ACE inhibitors by 54% of patients, and antiplatelet agents or warfarin sodium (Coumadin) by 93% of patients. Postoperative graft surveillance was done in 39% of patients. Cumulative graft patency was 73%, limb salvage was 85%, and mortality was 9%, with a mean follow-up of 17 months.Factors independently associated with increased graft patency included statin drug use (odds ratio [OR], 3.7; 95% confidence interval [CI], 2.1-6.4), male sex (OR, 2.8; 95% CI, 1.6-5.0), and graft surveillance (OR, 2.4; 95% CI, 1.3-4.5). Factors associated with decreased amputation rate were statin drug use (OR, 0.34; 95% CI, 6.15-0.77) and graft surveillance (OR, 0.23; 95% CI, 6.1-0.63). Factors associated with decreased mortality included graft surveillance (OR, 0.18; 95% CI, 0.1-0.56), whereas congestive heart failure (OR, 6.5; 95% CI, 2.5-17) and hemodialysis-dependent renal failure (OR, 29; 95% CI, 6.1-140) were associated with increased mortality. Kaplan-Meier analysis showed that only ACE inhibitors were associated with lower mortality (P =.05) CONCLUSIONS: Patients undergoing infrainguinal bypass are undertreated with respect to cardioprotective medications. ACE inhibitor use is associated with lower mortality, and statin drug use is associated with improved graft patency and limb salvage. Institution of consensus guidelines concerning these medications should be considered by all vascular specialists, including vascular surgeons.     

Clinical efficacy of rituximab for acute rejection in kidney transplantation: a meta-analysis

Objectives

This meta-analysis was undertaken to compare the efficacy and safety of pretransplant treatment with rituximab in sensitized patients receiving kidney transplantation.

Methods

PubMed, EMBASE, and Cochrane databases were searched to identify studies that used pretransplantation rituximab in eligible patients. The major outcomes included antibody-mediated rejections (AMR) after kidney transplantation and one-year graft survival rate. The meta-analysis was performed using fixed-effects model.

Results

Seven studies were identified including a total of 589 patients, of whom 312 were treated without rituximab, while 277 were treated with rituximab. In our meta-analysis, patients treated with rituximab had significantly fewer AMR after kidney transplantation [odds ratio (OR) 0.52, 95 % CI 0.28, 0.98, P = 0.04] and higher rate of one-year graft survival rates (OR 3.02, 95 % CI 1.14, 8.02, P = 0.03), indicating that rituximab is effective against acute rejection and enhances graft survival in kidney transplantation. No differences were noted in other efficacy and safety parameters in these two patient groups.

Conclusions

We demonstrated that preinduction with rituximab could significantly improve AMR and graft survival rates in sensitized patients undergoing kidney transplantation. Future prospective controlled studies are warranted to further understand rituximab’s role in kidney transplantation.     

Is acute rejection the key predictor for long-term outcomes after renal transplantation when comparing calcineurin inhibitors?

In the context of modern immunosuppressive regimens, the overall incidence of acute rejection may no longer be the most accurate surrogate marker for long-term kidney graft survival. The type, severity, timing, and clinical course of acute rejection each influence the impact of a rejection episode, and if renal function recovers fully, there appears to be no survival disadvantage. Randomized clinical trials in renal transplant patients have generally shown that there are fewer acute rejection episodes with tacrolimus compared with cyclosporine, although with contemporary regimens, including mycophenolate acid, this difference is less marked than previously. In randomized trials, kidney graft survival rates with cyclosporine and tacrolimus have proven similar. Large-scale registry analyses have consistently shown no graft survival benefit with tacrolimus vs cyclosporine, and indeed, 2 such analyses have reported significantly higher graft survival with cyclosporine-based immunosuppression compared with tacrolimus in living-donor kidney transplant patients receiving mycophenolate mofetil. There are no reports of improved patient survival with either calcineurin inhibitor after kidney transplantation. In conclusion, the perception of better efficacy with tacrolimus vs cyclosporine based on the incidence of acute rejection is not supported by a difference in graft or patient survival after kidney transplantation.     

心脏死亡供者供肝移植效果的荟萃分析

目的 评估心脏死亡器官捐献(DCD)供肝移植的效果.方法 检索美国国立医学图书馆国际性综合生物医学信息书目数据库(Pubmed/Medline数据库)、Embase数据库和Cochrane图书馆数据库中1950-2011年正式发表的英文文献,选取单中心研究.针对肝移植术后并发症的发生率,人、移植物存活率进行荟萃分析.结果 共纳入13篇单中心研究文献,包括5867例脑死亡器官捐献(DBD)肝移植和619例DCD肝移植.DCD肝移植术后发生胆道并发症的比值比(OR值)为2.5(95％可信区间为2.00～3.12),发生缺血性胆管炎的OR值为14.65(95％可信区间为6.51～32.99),发生原发性移植物无功能(PNF)的OR值为2.12(95％可信区间为1.33～3.36).DCD肝移植和DBD肝移植术后受者总体1年存活率分别为83.8％和87.2％,OR值为0.78(95％可信区间为0.59～1.02);移植物总体1年存活率分别为72.2％和82.4％,OR值为0.55(95％可信区间为0.45～0.68).DCD肝移植和DBD肝移植术后受者总体3年存活率分别为81.5％和78.9％,二者的差异无统计学意义(P＞0.05);移植物总体3年存活率分别为69.5％和73.6％,OR值为0.73(95％可信区间为0.56～0.94).结论 DCD肝移植术后胆道并发症发生率,尤其是缺血性胆管炎的发生率较高,但术后整体效果与DBD肝移植相当.     

Preemptive kidney transplantation in systemic lupus erythematosus

Preemptive kidney transplantation is associated with superior outcomes. Patients who have kidney failure due to systemic lupus erythematosus (SLE) may not receive a preemptive kidney transplant because of the concern for risk of disease recurrence with shortened graft and patient survival. We identified 8001 patients in the United Network for Organ Sharing dataset who underwent kidney transplantation between October 1987 and February 2009 with kidney failure due to SLE. Seven hundred thirty patients received a preemptive kidney transplant with 7271 patients who were on dialysis before transplantation; their mean ages were 40.0 ± 11.6 years and 36.9 ± 11.7 years, respectively, (P < .01). Women constituted 82.5% of preemptive and 81.4% of non-preemptive groups (P = .47). Preemptive transplant recipients were more likely to receive a living donor kidney transplant (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 3.3–4.5; P < .01). In unadjusted analyses, preemptive transplantation was associated with lower risk of recipient death (hazard ratio [HR] = 0.52; 95% CI = 0.38–0.70; P < .01). The difference remained significant after adjustment fr covariates (HR = 0.55; 95% CI = 0.36–0.84; P < .01). Graft survival was also superior among preemptive kidney transplant recipients in both unadjusted (HR = 0.56; 95% CI = 0.49–0.68; P < .01), and adjustment analyses (HR = 0.69; 95% CI = 0.55–0.86; P < .01). We concluded that preemptive kidney transplantation among patients with SLE was associated with superior patient and graft outcomes and should be considered when feasible.     

Impact of additional vascular reconstructions on survival of kidney transplants

Transplanting kidneys with complex vasculature is a demanding procedure and increases the risk of graft failure. The aim of the study was to investigate the outcome of additional vascular reconstructions performed during renal transplantation. In a retrospective analysis, we analyzed 720 consecutive renal transplantations between January 1995 and December 2004. One-week graft survival was the primary endpoint. One-week graft failure occurred in two (0.3%) reconstructed grafts. Arterial reconstructions had no significant effect on the 1-week graft survival [odds ratio (OR), 0.87; 95% confidence interval (CI), 0.85-0.9]. Univariate analysis revealed an increased risk of 1-week graft failure for venous reconstructions (OR, 7.15; 95% CI, 1.17-43.60), especially venous reconstruction without using the caval vein (OR, 27.24; 95% CI, 4.24-176.04). Arterial reconstruction had no increased risk of early renal graft failure. Venous reconstructions had a higher failure rate. This does not apply for reconstructions with the caval vein, of which the results were excellent.     

Negative impact of one-year anemia on long-term patient and graft survival in kidney transplant patients receiving calcineurin inhibitors and mycophenolate mofetil

BACKGROUND: The impact of posttransplant anemia (PTA) upon patient and graft survival remains controversial. The aim of this study was to assess the incidence of PTA 1 year after transplantation in patients treated with calcineurin inhibitors and mycophenolate mofetil, and to determine the impact of 1-year PTA upon long-term patient and graft survival. METHODS: Between January 1, 1999, and December 31, 2003, all patients with a functioning graft at 1 year, and who were receiving an immunosuppressive regimen based on calcineurin inhibitors and mycophenolate mofetil, were included in the study (n=339). Anemia was defined according to the World Health Organization criteria, that is, hemoglobin levels less than 13 g/dL for men and less than 12 g/dL for women. RESULTS: One hundred and eight of 339 were anemic at 1 year after transplantation (31.85%; group I). Independent predictors for 1-year anemia are donor's age and serum creatinine at 6 months. At last follow-up, that is, 69.4+/-17.7 months after transplantation, there had been a significant number of deaths in group I (n=7; 6.9%) compared with nonanemic patients (group II) (n=4; 1.73%; P=0.04). Mean allograft survival was significantly better in group II (70.7+/-17.1 months) compared with group I (66.4+/-18.7 months; P=0.03). Also, 12 graft losses (11.1%) were observed in group I and seven occurred in group II (3%; P=0.004). Independent predictors for allograft loss included delayed graft function and serum creatinine at 1 year. CONCLUSION: After kidney transplantation, the occurrence of PTA at 1 year is harmful, in the long term, to patient survival.     

Retrospective analysis of surgical complications following cadaveric kidney transplantation in the modern transplant era.

BACKGROUND: Risk factors for surgical complications (SCs) following kidney transplantation in the modern transplant era need to be identified to perform appropriate prophylactic interventions. METHODS: Records from 870 consecutive adult cadaveric kidney transplants done at a single centre were reviewed. SCs were classified into four groups: (i) vascular (12%, thrombosis or stenosis); (ii) haemorrhagic (12%); (iii) ureteral (7.5%, leaks and stenosis) and (iv) wound (16%, lymphocoeles or dehiscences). RESULTS: One or more SCs occurred in 299 (34%) patients, with multiple SCs in 65 (7.4%). By logistic regression analysis, recipient vessel atherosclerosis and delayed graft function (DGF) were significantly associated with both thrombotic complications [odds ratio (OR) 4, 95% confidence interval (CI), 1.4-11, P = 0.010 and OR 3.8, 1.3-12, P < 0.00001, respectively] and graft artery stenosis (OR 2.9, 1.2-6.8, P = 0.015 and OR 5.6, 2.3-13.4, P < 0.0001, respectively). Acute rejection increased the risk of graft artery or ureteral stenosis by 2.5 (CI 1.02-6.4, P = 0.045) and 3.3 (CI 1.1-10, P = 0.034), respectively. Older recipients were related to urinary leak (OR 1.04, CI 1.01-1.07, P = 0.011). Difficult bench surgery, DGF and the use of antiplatelet drugs increased the risk of bleeding by 3.6 (CI 1.9-6.4, P < 0.0001), 2.7 (CI 1.5-4.7, P < 0.0001) and 1.8 (CI 1.03-3.29, P = 0.038), respectively. Each month on dialysis increased the risk by 1.02 (CI 1.01-1.03, P = 0.002). Sirolimus increased the risk for wound SCs by 4.1 (CI 2.1-8.3, P < 0.0001) and obesity, retransplant and acute rejection were additional risk factors. CONCLUSIONS: Adult renal transplant recipients at risk for SCs can be identified by age, DGF, graft vessel and recipient atheromatosis, difficult bench surgery, obesity, rejection and the use of antiplatelet drugs and rapamycin.