Acute Renal Allograft Rejection Research Articles

Pretransplant Low CD3+CD25high Cell Counts or a Low CD3+CD25high/CD3+HLA-DR+ Ratio Are Associated With an Increased Risk to Acute Renal Allograft Rejection

Detection of markers predicting allograft rejection is important for risk assessment before kidney transplantation, as well as to minimize posttransplantation immunosuppression. We studied the expression of CD25, HLA-DR, CD134, CD62L, and CD44 by flow cytometry in CD4, CD8, and CD3 cells, from pretransplant blood samples from 91 transplanted patients accounting for 16 episodes of acute renal rejection in the first month after transplantation. None of the activation markers showed a significant association to acute rejection. Early rejectors showed less pretransplant CD3CD25 cells than nonrejectors (0.79%±0.50% vs. 1.51%±0.79% of CD3 cells; P=0.001) and a lower CD3CD25/CD3HLA-DR ratio (0.043±0.034 vs. 0.111±0.079; P<0.00001). When levels of CD25 cells fell below 0.7% of CD3 cells, the odds ratio of suffering an episode of acute rejection was 105 fold (95% confidence interval: 11.41-966.43, P<0.0001), with a sensitivity (true-positive results) of 0.63 and a specificity (true-negative results) of 0.98 for predicting the risk of acute rejection. Furthermore, when the CD3CD25/CD3HLA-DR ratio fell below 0.04, the odds ratio of suffering an episode of acute rejection was 7.71 fold (95% confidence interval: 2.29-25.97, P=0.001), with a sensitivity of 0.56 and a specificity of 0.86 for predicting risk of acute rejection. Our results suggest that low pretransplant levels of CD3CD25 cells or a low CD3CD25/CD3HLA-DR ratio could identify those patients with an increased risk of early acute allograft rejection. If these data can be independently confirmed, pretransplant CD3CD25 cells and the CD3CD25/CD3HLA-DR ratio might provide additional information for risk assessment before kidney transplantation.

Apolipoprotein A1 and C-Terminal Fragment of α-1 Antichymotrypsin Are Candidate Plasma Biomarkers Associated With Acute Renal Allograft Rejection

Current diagnostic methods of renal allograft rejection are neither sensitive nor specific. Needle biopsies are invasive and associated with patient morbidity. Thus, it is desirable to develop noninvasive tests to predict and diagnose rejection. Using a case-control approach, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to identify plasma proteins associated with renal allograft rejection. From each rejection patient (n=16), two plasma samples (one near the biopsy date and the other at a time postbiopsy) were compared. Biopsy-confirmed nonrejection patients (n=48) were further analyzed as controls. Antibody-based quantitative enzyme-linked immunosorbent assay was performed to validate candidate biomarker apolipoprotein A1 (Apo A1) in a subset of the original and a second cohort of biopsy-confirmed rejection (n=40) and nonrejection (n=70) patients. Twenty-two proteins/peptides showed significant differences between rejection and postrejection samples. Peptides 5191 Da and 4467 Da detected rejection with 100% sensitivity and 94% specificity. The 4467 Da peptide was identified as the C-terminal fragment of α-1 antichymotrypsin and a 28 kDa protein was determined as Apo A1. Both protein levels were significantly lower at rejection compared with postrejection. Protein levels of nonrejection patients were similar to the postrejection samples. Apo A1 enzyme-linked immunosorbent assay results showed significantly lower Apo A1 levels (P=0.001 for the original and P=4.14E-11 for the second cohort) at the time of rejection compared with nonrejection which coincides with the SELDI findings. Together α-1 antichymotrypsin, Apo A1, and the unidentified 5191 Da peptide provide a plasma molecular profile, and this is associated with acute cellular renal allograft rejection.

Characterization of acute renal allograft rejection by proteomic analysis of renal tissue in rat

Rapid and reliable biomarkers of renal allograft rejection have not been available. This study aimed to investigate biomarkers in renal allograft tissue using proteomic analysis. Orthotopic kidney transplantations were performed using Fisher (F344) or Lewis rats as donors and Lewis rats as recipients. Syngenic control group (Group I) constituted F344-to-F344 orthotopic kidney allo-transplantations (n = 8); and allogenic group (Group II) consisted of F344-to-Lewis orthotopic kidney allo-transplantations (n = 8). Renal tissues were harvested 7 days after transplantation. Samples were analyzed using 2-D electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry. 6 differentially expressed proteins were identified between allogenic group and syngenic control group. A rat model of acute renal allograft rejection was successfully set up. Differentially expressed proteins in renal allograft tissue of rat were detected using proteomic analysis and might serve as novel diagnostic and therapeutic targets in human. Quantitative proteomics, using MALDL-TOF-MS methodology has the potential to provide a profiling and a deeper understanding of acute renal rejection.

Elevated expression levels of ANXA11, integrins β3 and α3, and TNF‐α contribute to a candidate proteomic signature in urine for kidney allograft rejection

Kidney transplantation is the treatment of choice for end stage renal disease, with long-term allograft loss being the major obstacle, and for which potential treatments are based on a histological diagnosis. The problem is that markers for predicting graft rejection are limited in number, are invasive, and are quite non-specific. We have hypothesized that protein biomarkers might be discovered in the urine of patients when acute or chronic rejection might be occurring. We have established a workflow in which initial screening for candidate biomarkers is first performed using urine samples on large-scale antibody microarrays. This approach generated several dozen candidates. The next step is to qualify some of the strongest signals using the high-throughput Reverse Capture Protein Microarray platform. Four top candidates including ANXA11, Integrin α3, Integrin β3 and TNF-α, initially identified by the antibody microarray platform, were all qualified using Reverse Capture Protein Microarrays. We also used receiver operating condition (ROC) curves to independently quantify the specificity and sensitivity of these four analytes. The present data suggest that these novel four analytes in the urine, together or independently, may contribute to a robust and quantitative urine proteomic signature for diagnosing acute or chronic rejection of renal allografts.

Phenotypic Evaluation of B-Cell Subsets After Rituximab for Treatment of Acute Renal Allograft Rejection in Pediatric Recipients

Recently published pediatric trial of Rituximab for the treatment of CD20+ acute renal allograft rejection (AR) demonstrated transient depletion of circulating/intragraft B cells (Zarkhin et al., Am J Transplant 2008; 8: 2607). In this study, we have evaluated phenotypic definition of circulating B-cell subsets before and after standard of care and B-cell depletional AR therapies. We assessed peripheral B cells by flow cytometry at the time of AR and after AR treatment in 35 pediatric renal transplant recipients: 17 patients with AR who received Rituximab (R-AR; n=11) or steroid pulsing (S-AR; n=6), 18 stable patients with stable graft function with (iSTA; n=10) or without interval infection (hSTA; n=8), and 3 healthy volunteers. Infections increased memory (P=0.02) and CD19+/CD27⁻/IgD⁻ double negative (DN) B cells (P=0.02) and decreased naive B cells (P=0.01) in iSTA group compared to hSTA patients. Decrease in naive/memory B cells ratio at AR was observed compared with hSTA patients (P=0.01). One year after AR treatment, S-AR patients had persistently lower naive/memory B-cell ratio (P=0.01) and higher DN B cells (P=0.0001) than hSTA patients, whereas after R-AR treatment naive/memory B-cell ratio (P=0.6) and DN B cells (P=0.13) recovered to levels of hSTA patients. R-AR patients with sustained AR resolution (n=8) had trend toward better graft survival (P=0.06) and higher naive B cells (P=0.004) than R-AR relapsers (n=3). Increase in circulating memory B cells was seen in pediatric patients at AR. B cells persist as memory after S-AR treatment, whereas Rituximab resulted in repopulation of mostly naive B cells. The heterogeneity in B-cells reconstitution after rejection therapies deserves further investigation as a possible means to follow the clinical and immunologic outcomes of graft rejection.

Diagnosis of subclinical and clinical acute T‐cell‐mediated rejection in renal transplant patients by urinary proteome analysis

Noninvasive diagnosis of acute renal allograft rejection may be advantageous compared with the allograft biopsy. In this study, a multi-marker classification model for rejection was defined on a training set of 39 allograft patients by statistical comparison of capillary electrophoresis mass spectrometry (CE-MS) peptide spectra in urine samples from 16 cases with subclinical acute T-cell-mediated tubulointerstitial rejection and 23 nonrejection controls. Application of the rejection model to a blinded validation set (n=64) resulted in an AUC value of 0.91 (95% CI: 0.82-0.97, p=0.0001). In total, 16 out of 18 subclinical and 10 out of 10 clinical rejections (BANFF grades Ia/Ib), and 28 out of 36 controls without rejection were correctly classified. Acute tubular injury in the biopsies or concomitant urinary tract infection did not interfere with CE-MS-based diagnosis. Sequence information of identified altered collagen α(I) and α (III) chain fragments in rejection samples suggested an involvement of matrix metalloproteinase-8 (MMP-8). Biopsy stainings revealed matrix metalloproteinase-8 exclusively in neutrophils located within peritubular capillaries and sparsely, in the tubulointerstitium during rejection. The established marker set contains peptides related to tubulointerstitial infiltration seen in acute rejection. The set of urinary peptide markers will be used for early diagnosis of acute kidney allograft rejection marker in a multicenter phase III prospective study.

Macrophages and T lymphocytes are the predominant cells in intimal arteritis of resected renal allografts undergoing acute rejection

Background In acute renal allograft rejection, T-cell-mediated processes have been generally regarded as dominant. Although there is recent evidence that macrophages play important roles in acute vascular rejection, less is known about the exact proportion of immunocytes in the intimal arteritis of renal allografts with unfavorable outcomes. Methods By immunohistochemical staining using nine primary antibodies, we classified the proportions of infiltrating immunocytes in intimal arteritis and glomerulitis in five allografts resected because of acute irreversible graft failure. Results All five allografts had features of antibody-mediated rejection based on criteria established by the Banff classification. In intimal arteritis, CD3+ T-lymphocytes accounted for 30.6 ± 13.3% of the immunocytes and macrophages for 40.4 ± 9.2%. 45.4% of the T-cells were CD8+ cytotoxic T-cells. Neutrophils were also present but accounted for a relatively low proportion of the cells (8.8 ± 8.6%). B-cells and plasma cells all accounted for < 5% of the immunocytes. NK cells were readily detected (4.2 ± 4.2%). When we compared types of arteritis, the CD15+ neutrophils accounted for as many as 27.8 ± 15.1% of immunocytes in V3 vasculitis and only 1.0 ± 1.4% in V2 vasculitis. CD3+ T-lymphocytes accounted for 25.8 ± 7.3% of immunocytes in V3 vasculitis and 41.5 ± 7.9% in V2 vasculitis. In glomerulitis, the immunocytes were mainly macrophages (53.1 ± 9.1%) and neutrophils (34.6 ± 9.9%). Conclusion Macrophages and T-lymphocytes accounted for the highest percentage of immunocytes in the intimal arteritis of irreversible renal failure associated with antibody-mediated rejection. 45.4% of the T-cells were CD8+ cytotoxic T-cells. Neutrophils and NK cells were also present in these lesions. The proportion of neutrophils in V3 vasculitis was much higher than in V2 vasculitis. These observations suggest that besides macrophages and T-lymphocytes, neutrophils may also play a role in the more severe arterial lesion. To our knowledge this is the first report of this observation. Macrophages and neutrophils were the main inflammatory cells in the glomerulitis of acute rejection.

125 Acute Rejection in Renal Allografts With Delayed Graft Function (DGF) in the Era of T Cell Depleting Induction

ACUTE REJECTION IN RENAL ALLOGRAFTS WITH DELAYED GRAFT FUNCTION (DGF) IN THE ERA OF T CELL DEPLETING INDUCTION Usama T Hussein MD , Carlos R Franco MD, Juan C Calle MD, Fernando G Cosio MD, Hatem Amer MD. on Division of Nephrology and Hyper tension and the William J v Liebig Transplant Center, Mayo Clinic, Rochester MN, USA Introduc on: DGF is associat ed with worse long term renal allogra survival. With poor early allogra func on there is always concern for undiagnosed acute rejec on (AR). We rou nely biopsy DGF allogra s in the first week. With T cell deple ng agents we ost hypothesized that AR would be u nlikely in the first week p transplant Methods: Between January 2005 and December 2009 we performed 725 kidney alone trans plants who were ABO compa ble and with nega ve pre-transplant flow cross match. Sixteen (2.2%) pa ents had DGF, defined as dialysis within one week of transp lant, and had a biopsy. Results: Age 52.3 ± 13.2 year, Caucasians 15 (93.7 %), male 12 (75 %), deceased donor source 10 (62. 5%), re-transplant 4(25%). T cell deple ng agents were used in all pa ents, Alemtuzumab followed by tacrolimus and myco phenolate mofe l in 2 (12.5%) the remainder, rabbit An -thymocyte Globulin followed by tacrolimus mycophenolate mofe l, and cor costeroids. DGF was more common in recipients of deceased donor kidneys 20.4 % vs. 0.9 % p <0.001. AR was seen in 2 (12.5%) cases one AR 2A and the second was an body mediated rejec on. Other findings on ) biopsy included: 11 (68.7%) ATN, 1 (6.25%) normal and 2(12.5% biopsies showed donor transmi ed histological changes. Conclusion: In this study we con firm that ATN is the commonest histological finding in pa ents with DGF and more likely to occur in recipients of deceased donor kid neys. AR is uncommon early post ransplant with T cell deple ng agent induc on but can not be xcluded without performing early biopsies. t e

Effects of Sample Timing and Treatment on Gene Expression in Early Acute Renal Allograft Rejection

We have shown that genomic biomarkers in peripheral blood provide evidence of early graft rejection and may offer an important option for posttransplant monitoring, and we are working to improve this signature to maximize assay performance. This clinical refinement study (n=79) used gene expression profiling in a case-control design to compare whole blood samples between normal subjects (n=20) and patients with (n=20) or without (n=39) biopsy-confirmed acute rejection (BCAR). Gene expression in peripheral blood from subjects with BCAR before treatment differed significantly from that of normal subjects and transplant recipients without BCAR. Hierarchical clustering and principal component analysis showed that samples obtained 1 to 5 days after the start of treatment of BCAR were segregated across both groups before treatment or without BCAR and that this was closely related to the time lag between treatment and sampling. Genes differentially expressed during BCAR included FKSG49, LMAN2, NFYC, LIMK2, JUNB, NASP, MALAT1, ITGAX, HLA-J, FKBP1A, and RBMS1, and gene ontology analysis highlighted changes in networks related to cytoskeletal reorganization, apoptosis, and immune signaling, whereas after treatment change highlighted pathways of cellular metabolism, cell-cycle regulation, DNA damage, and apoptosis. Gene expression in the peripheral blood is associated with BCAR, and the pattern of expression changes rapidly after treatment. This may offer a potential tool for diagnosis of rejection and immunologic monitoring of response to treatment, which is now being evaluated in a large multicenter international study.

Polymorphisms in STAT4 increase the risk of acute renal allograft rejection in the Chinese population

Recently, the signal transducer and activator of transcription 4 (STAT4) gene have been associated with multiple autoimmune diseases. Taking into consideration that the different autoimmune diseases may share some common pathogenetic pathways, the aim of the present study was to evaluate the role of STAT4 rs7574865 polymorphism on acute allograft rejection. The present case-control study included 453 renal allograft recipients and 378 sex matched healthy controls. Genotyping was performed using a PCR based discrimination assay for the rs7574865 STAT4 SNP. No evidence of association was found between health controls and renal transplant recipients for the G/T or T/T genotype and wild type G/G. ( p = 0.431, two-tailed χ 2; OR = 0.894, 95% CI = 0.677–1.181). But among the transplant recipients, the G/T or T/T genotype was more common in transplant rejectors (acute allograft rejection) than nonrejectors who had mostly wild-type G/G genotype ( p = 0.003, two-tailed χ 2; OR = 0.542, 95% CI = 0.361–0.815). We also found a trend that the frequency of G/T or T/T genotype was also relatively more in the acute cellular mediated rejection than antibody mediated ones ( p = 0.049, two-tailed χ 2; OR = 0.466, 95% CI = 0.216–1.003). Thus, our data suggest that the rs7574865 STAT4 SNP is a genetic susceptibility variant for acute renal allograft rejection in the Chinese population.

Histopathology and outcome of acute humoral rejection in renal allografts

Our purpose was to see if histopathologic features of acute antibody-mediated rejection (AMR) in renal allografts have prognostic value; and to compare two-year graft survival with and without additional therapy with plasmapheresis and intravenous immunoglobulin (IVIG). We reviewed renal allograft biopsies taken within the first 6 months after transplant from patients with C4d positive AMR, performed between January 2000 to December 2005 (n=57). We formed two groups: Group 1: biopsied between 2003 and 2005 (n=26), when C4d staining was routinely performed and option for plasmapheresis and IVIG was available; Group 2: biopsied between 2000 and 2002 (n=31), retrospectively found to be C4d positive. Patients whose biopsies showed cortical necrosis or arterial fibrinoid necrosis had early graft loss. Other histopathologic features did not statistically correlate with graft loss. Overall, additional plasmapheresis/IVIG treatment did not show convincing improvement in graft survival or function at 2 years post-transplant, but all six patients with thrombotic microangiopathy (TMA) who received plasmapheresis/IVIG had functioning grafts at two-year follow-up.

Histopathology and outcome of acute humoral rejection in renal allografts

Histopathology and outcome of acute humoral rejection in renal allografts

Functional Genomic Analysis of Peripheral Blood During Early Acute Renal Allograft Rejection

Functional Genomic Analysis of Peripheral Blood During Early Acute Renal Allograft Rejection

CXCL10 and CXCL13 Expression were Highly Up-regulated in Peripheral Blood Mononuclear Cells in Acute Rejection and Poor Response to Anti-Rejection Therapy

Acute rejection is still one of the main complications which enhances the cost and the risk to renal graft failure. Chemokines, interacting with respective receptors, can recruit leukocytes into grafts and mediate allograft rejection. In this study, we aimed to analyze gene expression of chemokines including CCL5/RANTES, CXCL10/IP-10, CXCL13/BCA-1, and receptors of CCR5, CXCR3, CXCR5 in peripheral blood mononuclear cells (PBMCs) during acute renal allograft rejection Gene expression of all these chemokines and receptors in PBMCs were analyzed by real-time PCR from 14 stable recipients, 32 biopsy-proven acute rejection (AR), and 5 acute tubular necrosis (ATN). Gene expression of CCL5, CXCL10, CXCL13, and CCR5 were up-regulated both in AR and ATN group compared to stable recipients (fold change>2, P<0.05). Serum creatinine recovered to baseline level after anti-rejection therapy was defined as AR-sensitive and creatinine maintained above 200 μmol/L as AR-resistant. Expression of CXCL10 and CXCL13 were 5.98-, 2.94-, and 20.5, 10.8-fold change in AR-resistant and AR-sensitive compared to stable recipients, respectively. The expression of CXCL10 and CXCL13 was a twofold change in AR-resistant compared to AR-sensitive recipients (P<0.05). Five out of ten AR-resistant recipients lost graft function in the follow-up. CXCL10 and CXCL13 expression were highly up-regulated in PBMCs in acute renal allograft rejection, especially in poor response to anti-rejection therapy and detrimental prognosis.

Acute rejection associated with donor‐specific anti‐MICA antibody in a highly sensitized pediatric renal transplant recipient

Allograft rejection in HLA identical transplant recipients and in patients without detectable donor-specific anti-HLA antibodies has lead to the identification of non-HLA antigens as targets of the alloimmune response. MICA antigen has been recognized as an important non-HLA target in renal transplantation. Recent studies have shown that anti-MICA antibodies are associated with acute renal allograft rejection and failure. Current cross match procedures using donor lymphocytes fail to detect MICA antibodies. Transplant candidates are not routinely tested for pre-sensitization to MICA antigens nor are transplant donors typed for MICA alleles. Optimal classification and treatment of acute rejection associated with MICA antibody remains unknown. In this case report, we are the first to describe the clinical course and treatment of donor-specific MICA antibody associated with both Banff type II A ACR and AMR in a highly sensitized pediatric renal re-transplant recipient. This case also emphasizes the importance of pre-transplant screening for donor-specific MICA antibody especially in highly sensitized renal transplant patients.

Urinary Cell Levels of mRNA for OX40, OX40L, PD-1, PD-L1, or PD-L2 and Acute Rejection of Human Renal Allografts

The positive costimulatory proteins OX40 and OX40L and negative regulatory proteins programmed death (PD)-1, PD ligand 1, and PD ligand 2 have emerged as significant regulators of acute rejection in experimental transplantation models. We obtained 21 urine specimens from 21 renal allograft recipients with graft dysfunction and biopsy-confirmed acute rejection and 25 specimens from 25 recipients with stable graft function and normal biopsy results (stable). Urinary cell levels of mRNAs were measured using real-time quantitative polymerase chain reaction assays, and the levels were correlated with allograft status and outcomes. Levels of OX40 mRNA (P<0.0001, Mann-Whitney test), OX40L mRNA (P=0.0004), and PD-1 mRNA (P=0.004), but not the mRNA levels of PD ligand 1 (P=0.08) or PD ligand 2 (P=0.20), were significantly higher in the urinary cells from the acute rejection group than the stable group. Receiver operating characteristic curve analysis demonstrated that acute rejection is predicted with a sensitivity of 95% and a specificity of 92% (area under the curve=0.98, 95% confidence interval 0.96-1.0, P<0.0001) using a combination of levels of mRNA for OX40, OX40L, PD-1, and levels of mRNA for the previously identified biomarker Foxp3. Within the acute rejection group, levels of mRNA for OX40 (P=0.0002), OX40L (P=0.0004), and Foxp3 (P=0.04) predicted acute rejection reversal, whereas only OX40 mRNA levels (P=0.04) predicted graft loss after acute rejection. A linear combination of urinary cell levels of mRNA for OX40, OX40L, PD-1, and Foxp3 was a strong predictor of acute rejection in human renal allograft biopsies. This prediction model should be validated using an independent cohort of renal allograft recipients.

Rituximab in the treatment of acute cellular rejection of renal allograft with CD20-positive clusters in the infiltrate

A 31-year-old woman with nephronophthisis received a cadaveric kidney transplant, and was immunosuppressed with cyclosporine, azathioprine and steroids. Twelve days after transplant a biopsy showed acute rejection with vascular damage. She was treated with 3 pulses of methylprednisolone and change of immunosuppression to mycophenolate mofetil and tacrolimus, without improving graft function. At day 21, a second biopsy showed accentuation of interstitial and vascular rejection. Antibody-mediated rejection was suspected and plasmapheresis and rituximab were prescribed. Graft function improved rapidly. Staining for C4d was negative and there were no circulating antibodies against the donor. In the interstitial infiltrate there were clusters of B lymphocytes that accounted for 40% of cells, which was thought to be an ominous sign, as it has been associated with poor graft outcome. Acute T-cell-mediated rejection grade III (Banff 07) was diagnosed. Thirty-nine months after transplant her kidney function is stable with no other complication. This clinical case generates the hypothesis that rituximab may have a beneficial role in the therapy of acute cellular rejection when there are clusters of B lymphocytes in the infiltrate and a good response has not been obtained to conventional anti-rejection therapy.

Evaluation of the novel protein kinase C inhibitor sotrastaurin as immunosuppressive therapy after renal transplantation

Importance of the field: The prevalence of acute renal allograft rejection has decreased substantially in past decades due to new and more specific immunosuppressive compounds but improvements in long-term graft function have not been achieved. There is a large need for new immunosuppressive agents that lack toxicity of current agents such as calcineurin inhibitors but show high synergistic efficiency in preventing rejection processes.Areas covered in this review: This review summarizes data concerning the pharmacokinetics, pharmacodynamics and clinical efficacy of the new PKC inhibitor sotrastaurin with a focus on renal transplantation. The article contains information that has been presented at international transplant meetings and congresses and that has been published between 2006 and 2010. Additionally, current ongoing trials are described in detail.What the reader will gain: Immunosuppressive regimens after kidney transplantation consist of a combination of several agents in order to minimize drug toxicity. Therefore, the reader is presented with the most up-to-date/current developments in sotrastaurin applications in Phase I and II trials with emphasis on data maintained from studies that combined sotrastaurin with established agents such as mycophenolic acid and tacrolimus.Take home message: Several trials are ongoing and planned to determine the optimal immunosuppressive regimen to benefit from sotrastaurin's distinct mechanism of action.

Steroid Avoidance in Two-Haplotype-Matched Living Donor Renal Transplants with Basiliximab Induction Therapy

Background Induction therapy and haplotype matching are utilized to mitigate immunologic risk in renal transplantation. The incidence of acute rejection (AR) of renal allografts has been reported to be as low as 9.3% within the first year among two-haplotype-matched siblings with no induction and triple-drug maintenance immunosuppression. We report our use of basiliximab induction in a series of two-haplotype-matched living donor renal transplants (LDRT). Methods We retrospectively reviewed 25 patients who received a two-haplotype-matched LDRT with basiliximab induction therapy. The primary endpoints were acute rejection (AR) episodes at 6 and 12 months and 1-year patient and graft survival rates. The secondary endpoints were the incidence of delayed graft function (DGF), cytomegalovirus (CMV), and BK virus (BKV). Results The rate of AR at 6 months was 0% (0/25) and 4% (1/25) at 12 months. The 1-year graft and patient survival rates were 100%. The incidence of DGF was 4% (1/25), while the incidences of CMV and BKV were 0%. Conclusion Basiliximab induction therapy with a steroid-sparing regimen yields favorable results in two-haplotype-matched LDRT, including a notable reduction in the rates of AR as compared to triple-drug maintenance immunosuppression without induction. These patients have excellent graft survival with no increased incidences of secondary infections.

Possible Defect of T Suppressor Cell Subpopulation in Patients With Kidney Acute Rejection

CD8 +CD28 − forkhead box P3 (Foxp3 +) T suppressor (Ts) lymphocytes are antigen-specific cells capable of inducing tolerogenic antigen-presenting cells by up-regulation of inhibitory receptors immunoglobulin-like-transcripts −3 and −4 and down-regulation of costimulatory molecules. Our study sought to investigate the relation between the level of peripheral CD8 +CD28 −Foxp3 + Ts cells and kidney allograft outcomes. The project included 44 kidney transplantation patients. During the 6-month period following transplantation an acute rejection episode (ARE) was diagnosed in 11 patients based on biopsy results using the Banff criteria. Peripheral blood samples collected at 1 day before as well as 14 and 30 days after transplantation were tested for CD8 +CD28 −Foxp3 + T cells by means of flow cytometry. Values were considered significant when P < .05. Cytometric analysis did not show significant differences between the groups in pretransplant levels of peripheral CD8 +CD28 −Foxp3 + Ts cells ( P > .05); however, the posttransplantation analysis showed a higher mean level of Ts cells in nonrejection (NONARE) versus acute rejection (ARE) patients ( P < .0001). This observation suggested that dysfunction of CD8 +CD28 −Foxp3 + Ts cells observed in ARE patients may contribute to these episodes. Interestingly, we observed similar results with respect to peripheral CD4 +CD25 +Foxp3 + T regulatory cells in ARE patients, suggesting impairment of immunoregulatory mechanisms (especially within the inducible Foxp3 system) in this group, leading to acute renal allograft rejection episodes.