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.     

Is the lower cyclosporine concentration at 2 hours after dosing safe in kidney transplant recipients?

Objective

To determine the correlation between cyclosporine blood concentration at 2 hours after dosing (C2) and renal allograft function.

Materials and Methods

From 2008 to 2010, 1191 kidney transplant recipients (718 male and 473 female patients) were studied. The correlation between serum creatinine concentration and C2 blood concentration was stratified as 400, 600, 800, and 1000 ng/mL.

Results

The mean (SD) C2 was 620 (235) ng/mL, and serum creatinine concentration was 1.49 (0.68) mg/dL. At multivariate regression analysis, no significant correlation was observed between serum creatinine concentration and C2 blood concentrations of 600, 800, or 1000 ng/mL (P = .18, .57, and .76, respectively); however, it was associated at 400 ng/mL (P = .03). Moreover, 36.1% of 3159 samples demonstrated satisfactory renal allograft function despite low C2 blood concentration between 400 and 600 ng/mL.

Conclusion

During maintenance therapy, C2 blood concentration between 400 and 600 ng/mL is effective and safe for providing prophylaxis against rejection, and can improve long-term survival by decreasing cyclosporine toxicity.     

Cytotoxic flow cytometric crossmatch in renal transplantation: a single assay to simultaneously detect antibody binding and cytotoxicity

Objectives

The complement-dependent lymphocytotoxicity crossmatch (CDC-XM) detects cytotoxic parameters of preformed antibodies. The flow cytometric crossmatch (FCXM) is used to detect the binding of recipient antibodies to donor cells. Because these two assays provide different information, both methods are often performed to assess the compatibility of donor-recipient pairs. The aim of this study was to develop a single assay that can simultaneously detect antibody binding and cytotoxicity.

Methods

A procedure called cytotoxic flow cytometric crossmatch (cFCXM) that determines cell death and antibody binding simultaneously was developed. The assay was validated in parallel with extended incubation CDC-XM. Receiver operating characteristic analysis was used to determine the cut-off level. Furthermore, pretransplantation sera from seven recipients with pretransplantation donor-specific antibodies (DSA) and negative CDC-XM were retrospectively tested for cFCXM (4 without antibody-mediated rejection (AMR) and three with AMR).

Results

The optimal method for the simultaneous detection of antibody binding and cytotoxicity in a single assay has been determined. Four of four patients (100%) with pretransplantation DSA and without AMR had negative cFCXM in both parameters. Of three patients with pretransplantation DSA who developed AMR, two patients (66.7%) had positive B-cell cFCXM in both parameters, and 1 patient (33.3%) had positive T-cell cFCXM in a binding parameter only. The first patient had anti-DR9, DR53, DQ9, the second patient had anti-A11, DR12 and the last one had an anti-B46 in their pretransplantation sera. These 3 cases experienced biopsy-proven AMR after living-donor kidney transplantation.

Conclusion

The newly developed assay, cFCXM, can simultaneously determine cytoxicity and antibody binding using a single platform. Furthermore, this assay can detect clinically significant HLA alloantibodies undetectable by conventional crossmatches. The cFCXM could serve as a new tool for the detection of a recipient's alloantibodies.     

Insertion/deletion polymorphism of the angiotensin-converting enzyme predicts left ventricular hypertrophy after renal transplantation

Background

Kidney transplant recipients show a higher risk for cardiovascular complications, such as left ventricular hypertrophy and heart failure, leading to the premature death in many cases.

Methods

We investigated the contribution of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism to the development of left ventricular hypertrophy (LVH), an indicator of heart disease progression among kidney transplant recipients.

Results

We observed a significant correlation between graft function and left ventricular mass index. The occurrence of LVH or severe LVH was significantly greater among patients with at least one D-allele (ID or DD).

Conclusion

The use of ACE inhibitors or angiotensin receptor blockers seemed to be advantageous for patients with the ID and especially, the DD genotype.     

Treatment of acute antibody-mediated rejection: a single-center experience

Introduction

Acute antibody-mediated rejection (AMR) leads to graft loss. The combination of plasmapheresis (PP), intravenous immunoglobulin (IVIG), and rituximab (RTX) has been reported to be effective therapy.

Patients and methods

Between October 2005 and September 2009, 8 (4.7%) kidney transplant recipients developed AMR, diagnosed by severe acute rejection and extensive C4d staining in peritubular capillaries.

Results

All patients were treated with two to six sessions of PP with IVIG added after the last PP. In two patients, RTX was prescribed after PP and IVIG. Baseline immunosuppression was based on steroids, mycophenolate mofetil or azathioprine, and tacrolimus or cyclosporine or everolimus. The presence of subsequent significant decrease in anti-HLA class I antibodies was demonstrated in a highly sensitized patient before and after transplantation with PP treatment. An increase was observed before the diagnosis of AMR. After a mean follow-up of 10 months (range = 1-23), patient and graft survivals were 100% and 50%, respectively. Three patients lost their transplants to AMR refractory to treatment and one patient, due to interstitial fibrosis and tubular atrophy at 23 months after AMR. Finally, four patients recovered renal function, showing a mean serum creatinine of 2.2 ± 0.45 mg/dL.

Conclusions

Early diagnosis and treatment with PP, IVIG, and RTX may resolve AMR. PP before and after transplantation in high-risk patients may result in anti-HLA class I and class II antibody removal from plasma and prevention of AMR.     

The Expression of B-Cell Activating Factor Belonging to Tumor Necrosis Factor Superfamily (BAFF) Significantly Correlated With C4D in Kidney Allograft Rejection

Introduction

B-cell activating factor, belonging to the tumor necrosis factor (TNF) superfamily (BAFF), plays an important role in the development and survival of B lymphocytes. The present study was to investigate the correlation of BAFF and complement residue C4d in kidney allograft biopsies.

Methods

Transplant kidney biopsies as allograft were studied. 10 acute rejection (AR) cases, 3 interstitial fibrosis/tubular atrophy (IF/TA) cases, and 9 unknown etiology cases from January 1, 2001 to July 20, 2007 were analyzed. Transplanted kidneys were excised because of graft loss, and their pathological sections were studied. Ten other protocol biopsy specimens were studied. These recipients who received protocol biopsies had serum creatinine levels that were within normal range (normal value: <144 umol/L) from 2007. The serum creatinine levels of these subjects were within the normal range (<1444 μmol/L). BAFF, C4d, and immunoglobulin G (IgG) were detected by immunohistochemical stain methods. All were primary renal transplant recipients.

Results

In AR and IF/TA cases, BAFF was strongly stained, similar to C4d. And BAFF and C4d were distributed in the perinephric tubular epithelial cell cytoplasm and cytomembrane. In the unknown etiology sections and protocol biopsy sections, BAFF was weakly or not expressed, similar to C4d. In BAFF and C4d high expression sections, weak or moderate IgG deposition was also found.

Conclusion

BAFF may be associated with the development of antibody-mediated allograft rejection in kidney transplantation.     

Activation of Complement in the Discordant Heart Xenotransplantation of Pig-to-Monkey Model and the Impact of Intrathymic Inoculation of Xenogeneic Antigen Combined With Whole-Body γ-Radiation

Objective

This study investigated changes in complement in discordant heart xenotransplantation using a pig-to-monkey model as well as the impact of intrathymic inoculation (IT) with xenogeneic antigen combined with whole-body γ-radiation (WBI).

Methods

In this experiment, pigs and monkeys selected as donors and recipients, respectively, were randomly divided into three groups: a blank group (group A), a whole-body irradiation group (group B) and an irradiation plus intrathymic injection group (group C). In every group, monkeys underwent heterotopic heart xenotransplantation.

Results

The results showed that the survival of donor hearts in group C was significantly longer than that of group A (P < .01). In mixed lymphocyte reactions, there was a significant reduction of the stimulation index in group C compared with group A. After xenotransplantation, the level of xenoreactive antibody in group C rose slower than that in group A or group B (P < .01). After rejection, the levels of CD46 and C3 declined greatly.

Conclusions

These results suggested that pretreatment with IT and WBI induced T-cell immunosuppression, restraining elicited xenoreactive antibody production of both immunoglobulin M and immunoglobulin G classes. However, it did not hinder complement activation via the classical pathway during hyperacute rejection and consequent xenograft rejection.     

Mycophenolate mofetil monotherapy in liver transplantation

Aim

Calcineurin inhibitors (CI) are associated with significant morbidity in transplant recipients. The aim of this study was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) monotherapy in liver transplantation (LT).

Methods

We analysed 32 patients (24 males, 8 female, of mean age 55.7 years) who underwent LT between 1994 and 2003. In 29 patients immunosuppressive therapy was cyclosporine; in three patients it was tacrolimus. Eleven patients were submitted for LT due to hepatitis B cirrhosis; eight for hepatitis C cirrhosis, six for alcoholic cirrhosis, and seven for other diseases. In these patients, MMF was added gradually, simultaneously reducing the dosage of CI up to complete withdrawal. We considered the efficacy (decrease in serum creatinine) and the incidence of complications (acute and chronic rejection, leukopenia, diarrhea).

Results

Patients were converted to MMF after a median of 50 months after LT. MMF monotherapy was started after a median of 9 months in association with CI. Indications for switch to MMF monotherapy were adverse effects of CI (renal disfunction in 30 patients) and de novo tumoral evidence after LT in two patients. Median dosage of MMF was 750 mg twice daily (500-1500 mg). There was a statistically significant decrease in serum creatinine levels (2.02-1.7 mg/dL; P = .0001). Side effects were: leukopenia in five of 32 patients (15.6%), diarrhea in four of 32 patients (12.5%), and one acute rejection.

Conclusion

MMF monotherapy improved renal function and was not associated with a significant risk of allograft rejection. Side effects were mild with dose regimens up to 750 mg twice daily.     

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.     

Serum levels of interleukin-9 during acute rejection in liver transplantation

Introduction

Interleukin-9 (IL-9) has been cast as a player in autoimmunity, but its role in liver transplantation remains to be clarified. The aim of our study was to investigate the time course of IL-9 serum levels during hepatic allograft rejection.

Methods

IL-9 serum levels were determined in 34 healthy subjects and 50 hepatic transplant recipients. The patients were divided into two groups: group I was composed of 15 patients with acute rejection episodes, and group II, 35 patients free of this problem. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy.

Results

The concentrations of IL-9 were similar in the rejection and nonrejection groups over the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-9 serum levels than the controls at all times after liver transplantation.

Conclusions

These preliminary results suggest a lack of participation of IL-9 in human liver allograft rejection.     

The role of the altruistic unbalanced chain in exchange living donor renal transplantation: single-center experience

Background

The exchange donor program in renal transplantation is an efficient solution for recipients with a blood type or crossmatch-incompatible donor. However, this program has some difficulties to define unacceptable human leukocyte antigen matches, deteriorating clinical potential recipient condition, and withdrawal of donor consent. We analyzed the outcomes of exchange donor renal transplantation through the altruistic unbalanced chain.

Methods

Among 152 cases of exchange donor renal transplantation from 1991 to 2010 in our hospital, we performed 58 procedures through altruistic unbalanced chains. We compared their outcomes with the direct and balanced chain group. We analyzed retrospectively whether this program expanded the donor pool, seeking better immunologic, size, and age matching.

Results

The graft survival and acute rejection rates did not differ significantly in the two groups. Of 152 cases, 58 (38.2%) renal transplantations were performed through an unbalanced chain. Seventeen waiting list recipients were transplanted through an altruistic unbalanced chain. In blood type O recipients (n = 32), the causes of registration in the exchange program were ABO incompatibility (93.3%), and positive crossmatch (6.7%). Nine altruistic blood type O donors and 9 (28.1%) type O recipients underwent transplantations through this chain.

Conclusions

We suggest the altruistic unbalanced chain may expand the donor pool with advantages for difficult-to-match pairs. The disadvantages of type O recipients may be overcome through the use of an unbalanced chain. The altruistic unbalanced exchange transplantation program can help easy-to-match subjects, shortening the waiting periods.     

XM-ONE detection of endothelium cell antibodies identifies a subgroup of HLA-antibody negative patients undergoing acute rejection

Background

Kidney transplant recipients exhibiting antibodies (Ab) against either HLA or non-HLA antigens undergo frequent episodes of rejection and exhibit decreased long-term graft survival. The novel flow cytometry crossmatch kit XM-ONE, detects Abs to HLA antigens plus those directed to Tie-2-positive precursor endothelial cells (anti-endothelial cell antibodies, AECA). We studied the clinical importance of these lesser known antibodies.

Methods

We retrospectively analyzed 208 sera from 160 recipients of deceased donor grafts for AECA using non-donor peripheral blood endothelial progenitor cells as targets and Luminex methodology for HLA antibodies.

Results

AECA were detected in 64 patients (40%). A significantly higher proportion of patients showing a positive endothelial crossmatch experienced rejection (31 AECA-positive among 43 rejection cases, 72%) compared with those without rejection (33/117, 28.2%). Immunoglobulin M(IgM) predominated (66%) over IgG (14%) and IgG plus IgM (20%). HLA antibodies positively and significantly associated with rejection as expected. Of special interest were the 19 patients who presented with acute rejection episodes along with restricted AECA positivity. The relative-risk for an acute rejection episode with either AECA or HLA—13.87 and 2.43, respectively—was significant. When HLA was already positive, the relative risk for AECA was 1.24, a non-significant increase.

Conclusions

Our data identified AECA-positive patients that showed an increased risk to develop an acute rejection episode early after transplantation. Moreover, restricted AECA-positive patients with acute rejection are an important subgroup which otherwise may be wrongly labeled as non-humoral rejection. Among HLA-negative cases, AECA conferred a significantly greater risk for rejection.     

Transplantation with kidney paired donation to increase the donor pool: a single-center experience

Background

A living either related or unrelated donor transplant leads to a better outcome in terms of patient and graft survivals compared with one from a deceased donor. Desensitization protocols are expensive and labor intensive. The use of unrelated living donors has the greatest potential to increase the number of donors in the future, when no willing living donor is available due to blood group and/or human leukocyte antigen incompatibility. Herein, we have reported our results with a living donor exchange program.

Aims

To determine the feasibility and effectiveness of kidney paired donation (KPD) to manage patients with incompatible donors as well as present patient and graft survivals, serum creatinine (S.Cr) levels, and rejection episodes.

Results

Between June 2000 and December 2009, we performed KPD transplants in 36 recipients to avoid blood group incompatibility (n = 28) or to avoid a positive crossmatch (n = 8). At a median follow-up of 27.7 months (range, 5.83-119.8). The patient survival rate was 88.9% and the graft survival rate was 94.4%. Four patients developed acute cellular rejection episodes (11.1%) and 3 (8.3%) acute antibody-mediated rejection. At 1, 3, and 5 years, the mean S.Cr values were 1.42 ± 0.28 mg% (n = 28) 1.61 ± 0.51 (n = 22) and 1.24 ± 0.15 (n = 8), respectively.

Conclusions

The incidence of acute rejection episodes and patient/graft survivals were acceptable in our KPD program. The use of unrelated living donors has great potential to increase the number of donors in the future; a national KPD program should be encouraged in India.     

The significance of serum hepatocyte growth factor levels in planning follow-up of postoperative jaundice-free patients with biliary atresia

Purpose

The aim of this study was to clarify the significance of serum hepatocyte growth factor (HGF), interleukin (IL)-6, and IL-1 receptor antagonist (ra) levels in the evaluation of disease status in jaundice-free survivors with biliary atresia after Kasai operation.

Patients and Methods

Serum concentrations of HGF, IL-6, and IL-ra were measured in 31 long-term jaundice-free patients with biliary atresia after Kasai operation and 29 controls. Patients were divided into 4 groups: group A (n = 8), normal liver function; group B (n = 9), mild liver dysfunction without portal hypertension; group C (n = 9), moderate liver dysfunction with controllable portal hypertension; and group D (n = 5), receiving liver transplantation.

Results

Serum IL-6 levels were significantly higher in patients than in controls. There was no difference in serum IL-6 levels among groups B, C, and D. Serum IL-1ra levels were elevated according to liver dysfunction. Serum HGF levels in group D were significantly higher than in controls and the other groups. Serum hyarulonic acid levels were positively correlated with serum levels of IL-1ra and HGF.

Conclusions

Elevation of serum IL-1ra and HGF levels correlated with the progression of liver fibrosis and dysfunction. In particular, serum HGF levels could be used as a predictor for requiring liver transplantation.     

Early Sirolimus Therapy in Renal Transplant Recipients at High Risk: Is It Justified?

Background

We studied early sirolimus (SRL) therapy in renal transplant recipients at high risk after administration of antithymocyte globulin or interleukin-2 receptor blockade induction.

Patients and Methods

In 45 patients, SRL therapy was started within 1 month after transplantation. The primary indications for conversion of treatment from calcineurin inhibitors (CNIs)-mycophenolate mofetil (MMF)-steroid to SRL-MMF-steroid were biopsy-proved rejection (after treatment), CNI toxicity, CNI elimination, and acute tubular necrosis. Pediatric, geriatric, and other patients with medical comorbidities were not excluded.

Results

Post-SRL rejection episodes were reported in 22.2% of recipients including 15.6% who were resistant to steroid therapy. Mean (SD) follow-up after SRL therapy was 59.9 (8.1) months. Proteinuria greater than 2 g/d (P = .001), leukopenia (P < .001), hyperlipidemia (P < .001), and transaminases values (P = .02) increased significantly after SRL therapy. Graft survival was 88.8%, and patient survival was 93.3%. There was significant improvement in serum creatinine concentration and estimated creatinine clearance by the end of the study (P < .001). A high incidence of adverse effects and infections was noted post-SRL therapy, and the drug was discontinued in 31% of patients because of multiple adverse effects. At multivariate analysis, age, hypertension, nutritional status, bone marrow suppression, hyperlipidemia, and graft dysfunction were identified as risk factors for worse graft and patient outcome.

Conclusion

Early treatment with combined SRL-MMF-steroid may be effective as a CNI-free immunosuppression regimen in patients at high risk; however, there is a high rate of adverse effects during long-term follow-up.     

Neutrophil Gelatinase-Associated Lipocalin Is a New and Sensitive Marker of Kidney Function in Chronic Kidney Disease Patients and Renal Allograft Recipients

Background/aims

Few biomarkers exist to monitor chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL), a member of lipocalin family, has recently been proven useful to quantitate CKD. The aim of the study was to assess whether NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD and in kidney transplant recipients.

Methods

We studied possible relations between serum NGAL, creatinine, and estimated glomerular filtration rate (eGFR) in 80 nondiabetic patients with CKD stages 2 to 4; 80 nondiabetic kidney transplant recipients on a calcineurin inhibitor mycophenolate mofetil, or azathioprine as well as prednisone and in healthy volunteers (n = 32, mean age 50 years).

Results

Serum NGAL and creatinine values were significantly higher and eGFR significantly lower in kidney allograft recipients and patients with CKD compared with controls. NGAL rose gradually, reaching the higher value in stage 4 CKD. In univariate analysis serum NGAL was related to serum creatinine, hemoglobin, hematocrit, leukocyte count, and eGFR. Predictors of serum NGAL were creatinine and eGFR among patients with CKD. On univariate analysis serum NGAL was related to serum creatinine, urea, hemoglobin, hematocrit, white blood cell count, calcineurin concentration, eGFR, and albumin in kidney transplant recipients. On multiple regression analysis, predictors of NGAL were creatinine, calcineurin concentration, and high-sensitivity C-reactive protein. In healthy volunteers, serum NGAL correlated with age, serum creatinine, eGFR, and leukocyte count.

Conclusion

NGAL should be investigated as a potential early, sensitive marker of kidney impairment/injury, which might provide an additional accurate measure of kidney impairment in CKD and among transplant recipients, particularly at advanced stages.     

Role of Resistive Index Measurement in Diagnosis of Acute Rejection Episodes Following Successful Kidney Transplantation

Objective

This study was performed to evaluate the role of resistive index (RI) in the diagnosis of rejection episodes following successful kidney transplantation.

Materials and Methods

One hundred and one unrelated living first kidney allograft adult recipients (75 males and 26 females) of overall mean age of 39 years were enrolled and prospectively followed for 6 months. The measurement of RI by Doppler ultrasonography was performed in all patients on days 3 and 7 as well as at months 1, 3, and 6 in addition to when there was graft dysfunction. We determined serum creatinine and cyclosporine levels.

Results

Twenty-seven patients (26.7%) experienced 33 acute rejection episodes during the follow-up. There were significant differences between mean RI among patients with normal function vs rejection: 0.606 ± 0.065 vs 0.866 ± 0.083 (P < .05), respectively. Overall, elevated levels of cyclosporine, ischemic acute tubular necrosis (ATN), and renal artery thrombosis were observed in 8, 5, and 3 patients, respectively. No association was observed between these factors and RI.

Conclusions

RI was significantly higher in patients with acute rejection episodes. It had no association with ATN or cyclosporine toxicity. Hence, RI may be useful to diagnose acute renal allograft rejection following renal transplantation.     

First-year renal function predicts long-term renal allograft loss

Purpose

We performed a retrospective study to examine the impact on long-term graft survival of first-year posttransplantation renal function, as evaluated by serum creatinine.

Patients and Methods

We analyzed data from 1,273 adult kidney transplants performed between 1983 and 2008. All recipients >18 years old were included if their grafts had survived beyond 1 year, excluding patients simultaneously transplanted with other organs. Cox proportional hazards multivariable analysis was used to examine the relationship between first-year posttransplantation renal function and death-censored graft loss, adjusted for other variables. Renal function in the first year was expressed as serum creatinine levels at 1, 6, and 12 months as well as the change in creatinine between those 3 periods.

Results

Posttransplantation 1-month serum creatinine levels and change between 1 and 6 months were independent predictors of long-term graft loss. Multivariable analysis also identified donor age (increasing), acute rejection episode occurrence, recipient age at transplantation (decreasing), and gender (female) as independently predictive of graft failure, adjusting for other factors usually associated with graft loss, namely, pretransplantation time on dialysis, HLA mismatches, and delayed graft function. The predictive effect of creatininemia was sustained at 6 and 12 months, after adjusting for these covariates.

Conclusions

Posttransplantation serum creatinine levels at 1, 6, and 12 months were independent predictors of graft survival, suggesting that they could be considered as surrogate endpoints for long-term death-censored graft loss.     

Comparison between thymoglobulin and ATGAM as an induction agent in adult kidney transplantation: a single-center experience

Objective

The best antithymocyte globulin (ATG) preparation for induction suppression in kidney transplant recipients is still not clear. The aim of this study was to identify short- and long-term outcomes in kidney transplant recipients who received Thymoglobulin or ATGAM as an induction agent.

Methods

We retrospectively reviewed patients who underwent kidney transplantation from 1996 to 2010. Recipients were classified according to the ATG preparation.

Results

One hundred fifty-two patients (64.4%) received thymoglobulin and 84 (35.6%) received ATGAM. The occurrence of delayed graft function in patients receiving Thymoglobulin was higher than in patients receiving ATGAM (P = .005), but serum creatinine levels and acute rejection after kidney transplantation were not different between the two groups. The death-censored graft survival curve in Thymoglobulin recipients was higher than in ATGAM recipients (P = .027). Bacterial infection was a predisposing factor for graft survival (P = .008).

Conclusion

The efficacy of Thymoglobulin induction is generally better than that of ATGAM induction, and prevention of bacterial infections was just as important as the use of ATG because bacterial infection was an important risk factor for graft failure.     

Effect of Immunosuppressant Blood Levels on Serum Concentration of Interleukin-17 and -23 in Stable Liver Transplant Recipients

Introduction

T_H17 cells have been recently described to be involved in inflammatory and immune-mediated diseases, but there is no evidence of their role in human liver transplantation. Interleukin (IL)-23 is considered an inducer cytokine, whereas IL-17 is the main cytokine released by T_H17 cells. The aim of our study was to measure the serum levels of IL-17 and IL-23 in stable liver transplant recipients and examine the influence of immunosuppressant concentrations.

Materials and Methods

Serum levels of IL-23 and IL-17 were determined in 38 healthy subjects and 35 stable hepatic transplant recipients who were free of rejection episodes for at least 8 years. The results were analyzed according to the simultaneous blood levels of cyclosporine (n = 20) or tacrolimus (n = 15).

Results

No significant differences were observed in the serum levels of IL-17 and IL-23 between healthy subjects and transplanted patients. In addition, patients with low blood levels of tacrolimus (<6 ng/mL), but not cyclosporine, showed significantly lower serum levels of the 2 cytokines.

Conclusion

These preliminary results suggested a lack of activation of the T_H17 pathway, which was more pronounced among the patient subgroup treated with tacrolimus.