Rabbit antithymocyte globulin compared with basiliximab in kidney transplantation: a single-center study

Background

Induction therapy is used to reduce the incidence of acute rejection and to prevent or treat delayed graft function. We compared basiliximab with rabbit antithymocyte globulin (ATG) as induction therapies for kidney transplant recipients.

Methods

We retrospectively analyzed the clinical data from 514 patients who received ATG or basiliximab. The patients in the ATG group (n = 152) received ATG (1.5 mg/kg/d) for 5-7 days and those in the basiliximab group (n = 362) were given 2 doses of basiliximab (20 mg) on posttransplantation days 0 and 4. All patients received standard triple immunosuppressive therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids.

Results

There were statistically significant differences in the incidences of delayed graft function, 1-year acute rejection rate, death-censored graft survival, and patient survival between the 2 groups, even though the ATG group had more kidney transplants from deceased donors, higher levels of panel reactive antibodies, and more retransplantations. The incidences of cytomegalovirus (CMV) infection and parvovirus infection in the ATG group were higher than those in the basiliximab group. However, there was no statistically significant difference in the incidence of CMV disease between the 2 groups.

Conclusions

ATG is safe and efficacious for use in kidney transplant recipients. Our results suggest that ATG should be considered for induction therapy in high-risk patients, such as those who have a kidney allograft from a deceased donor, high levels of panel reactive antibodies, and are undergoing retransplantation.     

Basiliximab or Antithymocyte Globulin for Induction Therapy in Kidney Transplantation: A Meta-analysis

Objective

To compare efficacy and safety of basiliximab versus antithymocyte globulin (ATG) for induction therapy in kidney transplantation.

Methods

A literature search of the MEDLINE, EMBASE, CBMdisc, and Cochrane databases was used to identify randomized controlled trials that compared basiliximab and ATG for induction therapy in kidney transplantation. Inclusion criteria comprised: prospective randomized controlled clinical trials, follow-up time ≥12 months, randomized comparisons of ATG versus basiliximab as induction therapy in kidney transplantation. Meta-analytical techniques were applied to identify differences in outcomes between the two agents.

Results

A total of six studies involving 853 patients were identified. No differences between ATG and basiliximab were seen in terms of biopsy-proven rejection (relative risk [RR] 1.15, 95% confidence interval [CI] 0.88-1.52, P = .31), delayed graft function (RR 1.02, 95% CI 0.69-1.51, P = .93), graft loss (RR 1.15, 95% CI 0.73-1.80, P = .55), and patient death (RR 1.22, 95% CI 0.65-2.30, P = .54). But basiliximab had a lower incidence of infection (RR 0.87, 95% CI 0.78-0.97, P = .02) and neoplasm (RR 0.29, 95% CI 0.09-0.97, P = .04).

Conclusions

Basiliximab is as effective as ATG for induction therapy in kidney transplantation, whereas basiliximab has a lower incidence of infection. Basiliximab may be a safer and preferable option for induction therapy in kidney transplantation.     

Comparison of basiliximab and daclizumab with triple immunosuppression in renal transplantation

Purpose

Graft rejection is a serious problem despite immunosuppressive agents. Immunosuppression has been achieved with monoclonal antibodies (mAb) that bind specifically to the α subunit of the interleukin (IL)-2 receptor present on activated T lymphocytes. We explored the effects of two of the mAbs-daclizumab and basiliximab-on graft function.

Materials and methods

Our 1543 renal transplant recipients received baseline therapy with cyclosporine or tacrolimus plus corticosteroids and mycophenolate mofetil. In addition standard dosages intravenously of daclizumab (n = 156) or basiliximab (n = 45) in were administered intravenously to 201 renal transplant patients who included 122 men and 79 women of overall mean age of 30 ± 13.7 years.

Results

Patient and donor characteristics including age, sex, causes of renal failure, presence of comorbidities, panel-reactive antibodies, and numbers of human leukocyte antigen-mismatched were similar between the groups. During a mean follow-up of 27 ± 20 months, biopsy-proven acute rejection was observed in three patients in the basiliximab group and 23 in the daclizumab group. Cytomegalovirus infection occurred in 13 patients. There was no case of posttransplant lymphoproliferative disorder. Three polyoma BK nephropathies were detected in the daclizumab group. No hypersensitivity reaction occurred in either group. One-year patient survival was 100% in the basiliximab group and 99% in the daclizumab group, with graft survivals of 95% versus 94%, respectively. The mean creatinine levels at discharge were 2 mg/dL versus 2.3 mg/dL and at 12 months, 1.3 mg/dL versus 1.2 mg/dL, respectively.

Conclusions

Acute rejection episodes remain a significant risk factor for the development of graft dysfunction and poor long-term graft survival. IL-2R antagonists were effective antibody therapies. There was no apparent difference between basiliximab and daclizumab treatment.     

The Outcome of Induction Therapy With Monoclonal Antibodies in Kidney Transplantation Among Iranian Patients: A Prospective Study

Introduction

The administration of interlukin-2 receptor antagonists for induction therapy has reduced the incidence of acute rejection episodes in kidney transplantation. Although some studies have investigated the efficacy of these monoclonal antibodies, there is little experience among Iranian kidney transplant recipients.

Materials and Methods

Forty-three patients randomly divided into 2 groups were prospectively followed for 3.4 years. Eighteen patients received 2 doses of basiliximab (group I) and another 25 patients received 5 doses of daclizumab (group II). The posttransplantation complications, last serum creatinine level, as well as graft and patient survival rates were compared to investigate the efficacy of these therapies.

Results

Among 43 patients, 11.6% experienced acute rejection episodes: 22.2% in group I and 4% in group II (P > .05). In this study, 4.6% of recipients underwent graft nephrectomy: 11.1% in group I and 4% in group II (P > .05). The mortality rate was 4.6%: 5.5% in group I and 4% in group II (P > .05). The mean serum creatinine level was 1.47 ± 0.7 mg/dL. Although it was lower in group I, the difference was not significant. The 1-year graft and patient survival rates were 90.6% and 95.3%, respectively, with no significant differences between the groups.

Discussion

Although induction therapy with monoclonal antibodies may reduce the incidence of acute rejection episodes, graft and patient survival rates were unchanged compared with conventional therapies. Also, there were no significant differences between the results of induction therapy with basiliximab and daclizumab.     

Induction With Basiliximab in Renal Transplantation

Introduction

The use of monoclonal antibodies in renal transplantation for induction therapy has been associated with a marked reduction in acute rejection rates with an impact on graft and patient survivals.

Objective

We sought to evaluate the efficacy of renal transplant induction protocols using Basiliximab based on the rates of acute rejection episodes (ARE) and delayed graft function (DGF) of infectious complications in the first 6 months posttransplant, as well as patient and graft survivals.

Methods

We retrospectively evaluated all renal transplants performed between 2000 and 2008 that were primary grafts from cadaveric heart-beating donors, into recipients with a panel reactive antibody titer <5% and who were treated with an immunosuppression scheme based on cyclosporine, mycophenolate mofetil/mycophenolic acid plus corticosteroids, with (group 1) or without basiliximab (group 2).

Results

We enrolled 52 recipients in group 1 (induction with basiliximab) and 189 in group 2 (without basiliximab). The baseline characteristics were similar among the groups, except for time on dialysis which was longer in group 1 and the number of HLA matches, which was lower in group 1. The ARE rate was lower among group 1 (7.8% vs 27.8%; P = .001); rates of DGF and infectious complications were similar. There was no significant difference in graft and patient survivals.

Conclusion

In this study, induction with basiliximab was associated with a reduced rate rate of ARE, despite a lower number of HLA matches and a longer previous time on dialysis. The use of this induction modality was not associated with a greater rate of infectious complications.     

Bacillus Calmette-Guérin without maintenance therapy for high-risk non-muscle-invasive bladder cancer

Background

Bacillus Calmette-Guérin (BCG) is the standard intravesical treatment of high-risk noninvasive (Ta, T1, Tis) bladder cancer. Maintenance BCG is recommended for maximum efficacy.

Objective

We compared our results in a large cohort of high-risk bladder cancer patients who received BCG without maintenance with published results from randomized maintenance BCG trials.

Design, setting, and participants

A cohort of 1021 patients underwent restaging transurethral resection for high-risk (Ta, T1, Tis) bladder cancer.

Intervention

Patients received a 6-wk induction course of BCG therapy. Responding patients did not receive maintenance BCG. Relapsing patients were eligible for retreatment with BCG. All patients were followed for a minimum of 5 yr.

Measurements

End points were 5-yr tumor- and progression-free survival rates.

Results and limitations

Of 816 complete responders to induction BCG, 2- and 5-yr recurrence-free survival rates were 73% and 46%, respectively. The progression-free survival rate was 89%. Progression-free survival time was 56 mo (95% confidence interval, 55-58 mo). Thirty-two percent of the patients required another course of BCG therapy. We cannot exclude that maintenance BCG may benefit patients beyond 5 yr over induction BCG alone and selective BCG retreatments.

Conclusions

Our results with BCG treatment without maintenance of patients with high-risk non-muscle-invasive bladder cancer compare favorably with trials in which comparable patients received maintenance BCG.     

Prediction of acute cellular rejection by peripheral blood eosinophilia in pediatric living donor liver transplantation

Background

Acute cellular rejection (ACR) is a common cause of morbidity following liver transplantation. Several reports have evaluated the predictive value of peripheral blood eosinophilia as a simple noninvasive diagnostic marker for ACR. This study examined whether the relative eosinophil counts (REC) predicted ACR in pediatric living donor liver transplantation (LDLT).

Methods

One hundred three patients underwent LDLT between May 2001 and December 2007. ACR were diagnosed based on the pathological findings.

Results

The incidence of ACR was 46.6% (48/103); ACR was diagnosed an average of 13.5 days after LDLT. The average REC at 4 and 2 days before the onset ACR (n = 39) within 30 postoperative day (POD) was 4.3% and 7.3%, respectively, and 9.0% at the onset. Patients with ACR showed significantly higher levels of REC compared with those free of ACR (P = .039). REC thresholds of 10% at POD 7 displayed a sensitivity and specificity of ACR detection of 80% and 75%, respectively. Moreover, the accumulated morbidity ratio of ACR within 30 POD was significantly higher with REC >10% at POD 7 (P = .007).

Conclusion

ACR within POD 30 should be considered when REC is >10% at POD 7 after LDLT.     

Long-Term Efficacy of Induction Therapy With Anti-Interleukin-2 Receptor Antibodies or Thymoglobulin Compared With No Induction Therapy in Renal Transplantation

Background

Although the utility of antibody induction therapy has been demonstrated in clinical trials, the ideal regimen to use based on patient risk factors has not been fully elucidated. The objectives of this study were to determine the impact of either anti-interleukin-2 receptor antibodies (IL-2RA) or thymoglobulin induction therapies versus no induction therapy on acute rejection rates and on 3-year graft survival rates.

Methods

This retrospective analysis compared 3 patient groups—those who did not receive induction, those who received IL-2RA induction, and those who received thymoglobulin induction.

Results

Three hundred eleven patients were included in this study. Patients were well matched for demographic and immunologic characteristics in the noninduced and IL-2RA induction therapy groups; the thymoglobulin induction group included significantly higher risk patients. The acute rejection rates were significantly lower in the IL-2RA and thymoglobulin groups when compared with the no induction therapy group (28% vs 15% vs 41%, respectively; P = .001), which was confirmed with multivariate analysis. The 3-year graft loss rates (no induction 21% vs IL2-RA induction 19% vs thymoglobulin induction 25%; P > .50) and creatinine concentrations (no induction 1.8 ± 0.7, IL-2RA induction 2.0 ± 1.0, and thymoglobulin induction 1.9 ± 1.2; P = .47) were similar between all groups.

Conclusion

The use of induction therapy significantly reduces the incidence of acute rejection. The use of thymoglobulin induction equalizes 3-year graft survival rates in high-risk patients to those seen in low-risk patients receiving either no induction or IL-2RA induction.     

Prospective Clinical Trial Comparing Two Immunosuppressive Regimens, Tacrolimus and Mycophenolate Mofetil Versus Everolimus and Low-Dose Cyclosporine, in De Novo Renal Transplant Recipients: Results at 6 Months Follow-up

Objective

The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil (MMF) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus.

Patients and Methods

Sixty consecutive patients were prospectively assigned to receive tacrolimus and MMF (TAC; n = 30) or everolimus and low-dose cyclosporine (EVL; n = 30). Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter. Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7. Cyclosporine was dosed aiming at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter. All patients received induction with basiliximab and maintenance treatment with corticosteroids.

Results

At 6-months follow-up, patient survival rates (TAC 100% vs EVL 100%) and graft survival rates (TAC 96.7% vs EVL 93.3%) were not significantly different between the groups. Patients in the EVL group showed more acute rejection episodes, but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group. Among the observed side effects, hypercholesterolemia was significantly higher in the EVL group (total cholesterol: TAC 206 ± 38 vs EVL 250 ± 55 mg/dL; P < .003).

Conclusions

This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes, graft survivals, and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine. Dyslipidemia was significantly greater among patients who received everolimus.     

Once-a-day administration of everolimus is safe in de novo renal transplant recipients: 1-year results of a pilot study

Introduction

The half-life of everolimus is approximately 28 hours, but everolimus is generally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day everolimus (OD) with the standard twice a day administration regimen (BID) as immunosuppressive therapy in renal transplantation.

Methods

Forty-one de novo renal transplant recipients prospectively assigned to OD (n = 21) or BID (n = 20) treatment were followed for 1 year. In the OD group, everolimus was orally administered targeting a trough blood level of 2 to 5 ng/mL. In the BID group, everolimus was given twice a day targeting a trough blood level of 3 to 12 ng/mL. All patients also received induction with basiliximab and low-dose calcineurin inhibitor immunosuppression.

Results

At 1 year follow-up patient and graft survivals were 100%. The intention-to-treat analysis showed similar renal function between the two regimens: serum creatinine values for OD 1.54 ± 0.6 versus BID 1.48 ± 0.53 mg/dL (P = NS). Also the occurrence of acute rejection episodes was not significantly different: 4.8% in the OD versus 15% in the BID group, (P = NS). The median trough blood levels were significantly lower among the OD group: OD 4.5 versus BID 7.2 ng/mL (P < .001).

Discussion

This study demonstrated that once a day administration of everolimus achieved excellent patient and graft survival and good renal function without an increased incidence of acute rejection episodes.     

5-Year Results of a Prospective,Randomized, Single-Center Study of Alemtuzumab Compared With Rabbit Antithymocyte Globulin Induction in Simultaneous Kidney–Pancreas Transplantation

Introduction

The study purpose was to analyze 5-year outcomes in a prospective, randomized trial of alemtuzumab (ALEM) versus rabbit antithymocyte globulin (rATG) induction in simultaneous kidney–pancreas transplantation (SKPT).

Patients and Methods

From February 2005 through October 2008, a total of 46 SKPTs (45 portal-enteric drainage) were prospectively randomized to receive either single-dose ALEM (30 mg intraoperatively) or multiple-dose rATG antibody induction (starting intraoperatively, minimum of 3 doses administered) with tacrolimus/mycophenolate and/or steroids.

Results

Of 222 kidney transplant patients enrolled in the study, 46 received SKPTs; 28 (61%) received ALEM and 18 (39%) received rATG induction. Follow-up ranged from 54 to 98 months (mean, 69 months). There were no significant differences between the 2 groups in 5-year patient (82% ALEM vs 89% rATG), kidney graft (79% ALEM vs 72% rATG), or pancreas graft (64% ALEM vs 56% rATG) survival rates. Death-censored kidney (90% ALEM vs 75% rATG) and pancreas (71% ALEM vs 56% rATG) graft survival rates were likewise comparable (both, P = NS). Acute rejection (21% ALEM vs 44% rATG; P = .11) and major infection (39% ALEM vs 67% rATG; P = .13) rates were slightly lower in the ALEM group; cytomegalovirus infections were significantly lower (0% ALEM vs 17% rATG; P = .05). The incidence of late acute rejection was low in both groups. There were no differences in early pancreas thromboses (3.6% ALEM vs 11% rATG), postoperative bleeding (11% ALEM vs 0% rATG), other surgical complications, or readmissions between groups. In patients with functioning grafts, 5-year mean serum creatinine (1.4 ALEM vs 1.6 mg/dL rATG), calculated abbreviated Modification of Diet in Renal Disease glomerular filtration rate (55 ALEM vs 52 mL/min/1.73 m² rATG), glycosylated hemoglobin (both 5.4%), and C-peptide (2.2 ALEM vs 2.3 ng/mL rATG) levels were similar.

Conclusions

Single-dose ALEM and multiple dose rATG induction provided similar medium-term patient, kidney, and pancreas graft function and survival rates. ALEM induction may be associated with less acute rejection and major infection over the long term.     

A high model for end-stage liver disease score should not be considered a contraindication to living donor liver transplantation

Objective

To analyze the outcomes of patients with high Model for End-Stage Liver Disease (MELD) scores who underwent adult-to-adult live donor liver transplantation (A-A LDLT).

Materials and Methods

From September 2002 to October 2010, a total of 152 adult patients underwent A-A LDLT in our institution. Recipients were stratified into a low MELD score group (Group L; MELD score ≤30) and a high MELD score group (Group H; MELD score >30) to compare short-term and long-term outcomes.

Results

Of the 152 adult patients who underwent A-A LDLT, 9 were excluded from the analysis because they received ABO-incompatible grafts. Group H comprised 23 and Group L 120 patients. The median follow-up was 21.5 months (range, 3 to 102 m). The mean MELD score was 15.6 in Group L and 36.7 in Group H. There were no significant differences in the mean length of stay in the intensive care unit (Group L: 3.01 days vs Group H: 3.09 days, P = .932) or mean length of hospital stay (Group L: 17.89 days vs. Group H: 19.91 days, P = 0.409). There were no significant differences in 1-, 3-, or 5-year survivals between patients in Groups L versus H (91.5% vs 94.7%; 86.4% vs 94.7%; and 86.4% vs 94.7%; P = .3476, log rank).

Conclusion

The short-term and long-term outcomes of patients with high MELD scores who underwent A-A LDLT were similar to those of patients with low MELD scores. Therefore, we suggest that high MELD scores are not a contraindication to LDLT.     

Living Donor Liver Transplantation for Hepatocellular Carcinoma: Long-Term Results Compared With Deceased Donor Liver Transplantation

Objective

Living donor liver transplantation (LDLT) may represent a valid therapeutic option allowing several advantages for patients affected by hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). However, some reports in the literature have demonstrated worse long-term and disease-free survivals among patients treated by LDLT than deceased donor liver transplantation (DDLT) for HCC. Herein we have reported our long-term results comparing LDLT with DDLT for HCC.

Patients and Methods

Among 179 patients who underwent OLT from January 2000 to December 2007, 25 (13.9%) received LDLT with HCC 154 (86.1%) received DDLT. Patients were selected based on the Milan criteria. Transarterial chemoembolization, radiofrequency ablation, percutaneous alcoholization, or liver resection was applied as a downstaging procedure while on the waiting list. Patients with stage II HCC were proposed for LDLT.

Results

The overall 3- and 5-year survival rates were 77.3% and 68.7% versus 82.8% and 76.7% for LDLT and DDLT recipients, respectively, with no significant difference by the log-rank test. Moreover, the 3- and 5-year recurrence-free survival rates were 95.5% and 95.5% (LDLT) versus 90.5% and 89.4% (DDLT; P = NS).

Conclusions

LDLT guarantees the same long-term results as DDLT where there are analogous selection criteria for candidates. The Milan criteria remain a valid tool to select candidates for LDLT to achieve optimal long-term results.     

Antithymocyte globulin induction therapy in heart transplantation: prospective randomized study of high vs standard dosage

Background

In cardiac transplantation, high-dose antithymocyte globulin (ATG) induction therapy as short-term rejection prophylaxis has not been used.

Objective

To evaluate the efficacy and safety of intraoperative use of single high-dose ATG induction therapy after heart transplantation.

Patients and Methods

Fourteen patients received single high-dose ATG therapy plus shortened standard therapy (group1), and 16 patients received ATG standard therapy (group2).

Results

No perioperative deaths were reported. During follow-up, 3 deaths were recorded. Five- year patient survival was 92.8% in groupl vs 85.7% in group2 (P = .34). The mean (SD) number of acute rejection episodes per patient was 2.5 (2.2) in the high-dose ATG group vs 2.7 (2.5) in the standard therapy group (P = .83), with 5-year freedom from acute rejection of 45.5% in group 1 vs 35.6% in group 2 (P = .85). Infections were observed in 6 patients in group1 and in 8 patients in group2 (P = .69). Malignant disease was diagnosed in 1 patient in the high-dose group and 3 patients in the standard therapy group (P = .35). Chronic allograft vasculopathy was recognized in 4 patients (28%) in group1 and 8 (50%) in group2 (P = .05). Five-year actuarial freedom from allograft vasculopathy was 69.2% in the high-dose ATG group vs 50.0%% in the standard therapy group (P = .35).

Conclusions

High-dose ATG for prevention of rejection episodes is safe and efficacious, with a lower rate of early and late complications, in particular, graft vasculopathy.     

Which score system can best predict recipient outcomes after living donor liver transplantation?

Introduction

Many scoring systems have been suggested to predict the outcomes of deceased donor liver transplantations. The aims of this study were to compare the Model for End-Stage Liver Disease (MELD) score with respect to other scores among patients who underwent living donor liver transplantation (LDLT) seeking to evaluate the best system to correlate with postoperative outcomes after LDLT.

Methods

We analyzed retrospectively data from 202 adult patients who underwent LDLT from January 2008 to July 2010. We calculated preoperative MELD, MELD-sodium, MELD to serum sodium ratio (MESO), integrated MELD, United Kingdom MELD, Child-Turcotte-Pugh, Acute Physiology and Chronic Health evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores in all patients. We analyzed the correlation of each score with postoperative laboratory results, as well as survival at 1, 3, 6 and 12 months after LDLT.

Results

There was significant positive correlation between all scores and peak total bilirubin during the first 7 days after LDLT. The MELD score showed the greatest correlation with peak total bilirubin (r = 0.745). APACHE II and SOFA scores at 6 months and 1 year after LDLT and MESO score at 1 year after LDLT showed acceptable discrimination performance {area under the receiver operating characteristic curves (AUC) >0.7, while other scoring systems showed poor discrimination. However, the AUCs of each score were not significantly different from the MELD score AUC.

Conclusion

The MELD score most correlated with total bilirubin after LDLT, while the APACHE II and SOFA scores seemed to correlate with mortality after LDLT.     

Quality of Life and Problems Affecting Recipients More Than 10 Years After Living Donor Liver Transplantation

Background

We initiated living donor liver transplantation (LDLT) in 1991, allowing us to examine issues related to long-term survival. The aim of this study was to review the long-term outcomes of LDLT in children.

Patients and Methods

We performed 116 LDLT from 1991 to present, including 17 recipients who survived >10 years. They were evaluated for growth, immunosuppressive therapy, complications, and quality of life (QOL).

Results

The average age at LDLT was 5.4 years (range, 6 months to 17 years), with a present average age of 17.2 years (range, 11-28 years). At the time of LDLT, 6 recipients had growth retardation with body weights low for age by 2 standard deviations (SD). However, 4 of 6 recipients who underwent LDLT before age of 2 years caught up, reaching average heights and body weights for their ages. Among 6 recipients who were diagnosed with acute rejections by biopsy >5 years after LDLT, 5 improved after steroid pulse therapy. One recipient with a steroid-resistant acute rejection was administered deoxyspergualin after steroids. Chronic rejection was not observed in this series. One recipient has not required immunosuppressive therapy for >4 years with a good present condition.

Conclusion

The majority of LDLT recipients achieved a good QOL during long-term survival; they are pursuing normal studies.     

Use of High-Dose Human Immune Globulin in Highly Sensitized Patients on the Kidney Transplant Waiting List: One Center's Experience

Introduction

Transplant rates are low among highly sensitized patients with preformed anti-HLA antibodies, because of the additional immunologic barrier, the increased risk of rejection, and the greater chance of early graft loss. Intravenous infusion of pooled human immune globulin (IVIG) is immunomodulatory, neutralizing circulating antibodies and reducing rejection rates, two factors that may improve long-term transplantation outcomes.

Methods

We selected for high-dose IVIG treatment (1 g/kg monthly for 4 months) 10 adult, stage V, highly HLA-sensitized (PRA, historical >80% and current 56%-100%) chronic kidney disease patients listed for kidney transplantation with a mean waiting time of 7.5 years. They spanned age of 29-52 years. Anti-HLA titers were monitored monthly before each treatment and 1 month after the last IVIG dose; afterwards, patients were placed on an urgent list and followed for their transplant renal function and rejection episodes.

Results

Although 1 subject was transplanted after the first dose of IVIG, 9 patients completed the study, but their PRA decreased only insubstantially, namely, 14.4% (range, 8%-28%). During 6-12 months follow-up, 6 patients were considered for transplantation (negative crossmatch); 5 received kidneys and 1 was disqualified due to infection. The recipients were treated with antithymocyte globulin (n = 3) or basiliximab (n = 2) as well as tacrolimus/mycophenolate/steroids for baseline immunosuppression. Protocol biopsies (months 1, 3, and 6) in 4 patients (1 denied consent) revealed subclinical acute rejection and C4d positivity in most cases, either repeatedly or in the final biopsy. However at 6-12 months the mean serum creatinine concentration averaged 1.5 ± 0.4 mg/dL.

Conclusion

High-dose human IVIG reduced PRA poorly, but short-term transplantation outcomes were encouraging. Surveillance biopsies are advised for sensitized kidney recipients due to the frequent appearance of rejection, particularly of the antibody mediated type.     

The risk factors to predict acute rejection in liver transplantation

Purpose

The aim of this study was to evaluate risk factors for an acute cellular rejection episode (ARE) among adult liver transplant (OLT) patients.

Materials and methods

We retrospectively reviewed 110 consecutive patients who underwent OLT between May 2007 and December 2010. The diagnosis of ARE was based upon clinical and biochemical data; liver biopsy was only performed when clinical presentation was equivocal. We recorded donor and recipient characteristics, perioperative immune status, and postoperative laboratory data. Forty patients (36.4%) who suffered a clinical rejection episode and received pulsed or recycled steroid therapy (R group), were compared with 70 (63.6%) free of rejection (N group).

Results

The mean age of R recipients was 46.61 ± 9.97 years, which was younger than the N group (51.86 ± 8.37, P = .005). R group patients displayed a lower pre-OLT creatinine (P = .016) and higher alanine aminotransferase (P = .048). Cox regression model showed recipient age to be the only significant factor to predict ARE (odds ratio = 1.071, P = .003). The cutpoint of age was 46 years by receiver operating characteristic analysis. Patients younger than 46 years showed higher initial CD8⁺ T-cell counts (P = .038).

Conclusion

Recipient age was significantly associated with ARE; younger patients showed higher CD8⁺ lymphocyte counts than older patients. More aggressive immunosuppression should be considered for younger recipients to prevent ARE.