Acute Rejection Group Research Articles

Serum Level of Soluble Fibrinogen-Like Protein 2 in Renal Allograft Recipients With Acute Rejection: A Preliminary Study

BackgroundSoluble fibrinogen-like protein 2 (sfgl2), which is mainly secreted by T cells, is a novel effector of regulatory T cells with immunosuppressive functions. The aim of this study was to investigate serum levels of sfgl2 among renal allograft recipients. MethodsFrom November 2010 to August 2011 we retrospectively divided 47 renal allograft recipients into an acute rejection (n = 19) versus a stable group (n = 28) according to allograft biopsy results, using the Banff 2007 classification. The acute rejection group was subdivided into grade I (n = 8) versus grade II T-cell–mediated (n = 6) or antibody-mediated rejection episodes (n = 5). Peripheral blood samples were collected at the time of biopsy. Fourteen healthy volunteers were included as normal group controls. Serum levels of sfgl2 were analyzed by enzyme-linked immunosorbent assay. ResultsSerum levels of sfgl2 were increased among renal allograft recipients suffering from biopsy-proven acute rejection episodes (61.91 ± 45.68 ng/mL), versus those with stable allografts (38.59 ± 19.92 ng/mL, P < .05) or healthy volunteers (29.10 ± 18.08 ng/mL, P < .05). The sfgl2 level was significantly higher among patients with antibody-mediated (118.48 ± 55.54 ng/mL) than T-cell–mediated acute rejection episodes (41.71 ± 16.44 ng/mL, P < .01). Serum sfgl2 levels were remarkably elevated in patients with grade II (51.87 ± 19.13 ng/mL) versus grade I T-cell–mediated rejection (34.10 ± 9.26 ng/mL, P < .05). ConclusionsSerum sfgl2 levels were increased among renal allograft recipients with acute rejection episodes to an extent dependent upon the pathological type and severity of the response.

Indoleamine, 2-3 Dioxygenase Activity Could Be an Early Marker of Graft Rejection in Heart Transplantation

BackgroundThe indoleamine, 2-3 dioxygenase (IDO) is an inducible intracellular enzyme with immunosuppressive effects mainly on lymphocyte populations. It has been postulated that indirect determination of IDO serum activity may be a marker of renal graft rejection, but its potential usefulness in heart transplantation (HT) is unknown. MethodsThis longitudinal study included 98 HT patients (83% males) who survived ≥1 year. Mean age was 54.14 ± 11.57 years. Serum IDO activity was analyzed one month after HT by means of high performance liquid chromatography and correlated with the cumulative incidence of acute rejection (AR) during one-year follow-up. AR was defined as biopsy-proven ≥ ISHLT grade 2R rejection or empirically treated non-biopsy-proven rejection. The study sample was divided into two groups: AR group (n = 51), including patients who experienced at least one AR episode during the first year after HT; No-AR group (N = 47), including the remaining patients. ResultsMean serum IDO activity one month after HT was significantly higher (P = .021) in the AR group (3.32 ± 1.56) than in the no-AR group (2.62 ± 1.35). No significant association between serum IDO activity and gender (male: 3.1 ± 1.56, women: 2.43 ± 0.99, P = .092), recipient age (r = −.07, P = .943) or donor age (r = 0.108, P = 0.293) was observed. By means of binary logistic regression, an odds ratio of 1.4 [CI 95%: 1.033-1.876, P = .03] per unit increase of act-IDO was estimated, with no significant modification upon forced adjustment for age and sex. Mean glomerular filtration rate 1 month after HT was 67.01 ± 28.51 mL/min/m2. No significant correlation between this parameter and serum IDO activity was observed (r = .160, P = .117). ConclusionsOur study suggests that serum IDO activity one month after HT might be associated with a higher risk of AR during one-year follow-up. This association seems to be independent of recipient gender, age or renal function.

C4d Deposits in Acute “Cell-Mediated” Rejection: A Marker for Renal Prognosis?

BackgroundAccumulation of C4d along peritubular capillaries (PTC) of renal allografts is normally attributed to antibody-mediated rejection. The prognostic implication of these deposits associated with “cell-mediated” rejection on graft survival remains uncertain. Our study aims to evaluate the impact of C4d deposits along PTC of patients with acute cell- mediated rejection on graft function and survival. MethodsWe retrospectively analyzed patients transplanted between 2005 and 2010 with histopathologic diagnosis of acute rejection (AR). Eleven patients with “pure” antibody-mediated rejection were excluded. The remaining 79 patients were divided into two groups according to type of AR by Banff 2003 criteria: type I (69.6%) versus type II (30.4%). In each group, comparisons were made between C4d-negative (−) and C4d-positive (+) biopsies. ResultsFifty-five patients presented with type I AR: 35 (63.6%) C4d− and 20 (36.4%) C4d+. Twenty-four patients presented with type II AR: 13 (54.2%) C4d− and 11 (45.8%) C4d+. In the type I AR group, graft survival at the first and second years was similar in C4d− and C4d+ patients (94% and 91% versus 75% and 75%, respectively, log-rank P = .26). No differences were encountered in estimated glomerular filtration rate (eGFR) between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 14.7% of C4d− patients versus 25% in C4d+ patients (P = NS). In the type II AR group, graft survival at the first and second years was similar in C4d− and C4d+ patients (85% and 85% versus 72% and 61%, respectively, log–rank P = .50). No differences were encountered in eGFR between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 30.8% of C4d− patients versus 45.5% in C4d+ patients (P = NS). ConclusionOur results suggest that detection of C4d staining in acute “cell-mediated” rejection does not imply a worse renal prognosis.

TIPE2, a Novel Biomarker for Clinical Chronic Kidney Allograft Rejection

Tumor necrosis factor-a--induced protein 8-like 2 (TIPE2) has an essential role in immune homeostasis, yet the relationship between TIPE2 expression and allograft rejection has not been addressed. Dependent on clinical diagnosis, 96 kidney transplant recipients were divided into three groups, long-term survival group, acute rejection group (AR) and chronic rejection group (CR). Thirty-two healthy volunteers were used as a control group. The expression of TIPE2 in peripheral blood mononuclear cells (PBMC) and kidney biopsy samples was performed using reverse transcript-polymerase chain reaction, immunohistochemistry and immunofluorescence. The expression of TIPE2 in PBMC of CR group was significantly higher than that of the healthy control (P < 0.001), but TIPE2 expression in AR group was lower than that of control individuals (P < 0.05). The renal expression of TIPE2 in allograft tissue of CR was significantly lower and its expression in AR slightly lower than in normal kidneys. The positive correlation between TIPE2 expression in PBMCs and the CR of allo-kidney grafts indicates that detection of TIPE2 in the blood samples may be used as one of the diagnosis molecular markers in clinical monitoring kidney chronic rejection.

Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model

Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4(+)CD25(+) regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were recipients. Rats were randomly assigned to the following four groups: control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body irradiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased significantly to (459.2±76.9) U L(-1), total bilirubin increased to (124.1±33.7) μmol L(-1) (P<0.05) and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly to 1.50%±0.50% (P<0.05) compared with the other groups. Analysis of the T cell subpopulations in the acute rejection group varied from the other groups. Histological analysis showed typical changes of acute rejection in the acute rejection group only. Preconditioning of the donors with total body irradiation eliminated passenger lymphocytes of the liver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.

Predicting acute rejection in transplanted liver with virtul touch tissue quantification technique: a preliminary study

Objective To investigate the viability of virtual touch tissue quantification (VTQ)technique in the prediction of acute rejection in transplanted liver.Methods One hundred and eighteen patients enrolled in the study were categorized into four groups:normal control (n =31),cirrhosis ( n =29),transplanted liver with acute rejection (n =28),transplant liver without any complications (n =30).All the patients were confirmed by pathology or clinical results.The VTQ of right robe of liver was obtained by a ultrasound system with VTQ technique and the data was compared among the four groups.Results The VTQ was (1.10 ± 0.29)m/s,(1.33 ± 0.33) m/s,(1.81 ± 0.47) m/s and (2.12 ± 0.59) m/s in normal control,transplanted liver without any complications,transplanted liver with acute rejection and cirrhosis group,respectively.It was significantly different in all four groups (P＜0.01).Patients with acute rejection were associated with the increase of the VTQ values (P＜0.01).Using a cutoff of VTQ＞1.36 m/s measured in the transplanted liver for prediction of acute rejection,the sensitivity and specificity were 82.1％ and 68.2％.Conclusions VTQ technique may have some clinical value in evaluation the acute rejection in transplanted liver. Key words: Ultrasonography; Liver transplantation; Graft rejection; Virtual touch tissues quantification

Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients

Gene polymorphisms of cytotoxic T lymphocyte associated antigen 4 (CTLA4) play an influential role in the graft rejection and long-term clinical outcome of organ transplantation. We investigated the associations of five CTLA4 single nucleotide polymorphisms (SNPs) (rs733618T/C, rs4553808A/G, rs5742909C/T, rs231775G/A, rs3087243G/A) on the early acute rejection (AR) of Chinese deceased donor renal transplantation recipients. Genotyping of the CTLA4 SNPs was performed in 167 deceased donor renal transplantation recipients. Each patient underwent a 6-month follow-up observation for AR. The incidence of AR during the 6months post-transplantation was 26.9% (45 out of 167 patients). Patients experiencing AR were found to have a higher frequency of the rs733618TT genotype and T allele (p=0.000 and p=0.002, respectively). While the haplotype CACAG was merely observed in non-AR group (corrected p=0.000), the frequency of haplotype TACGG was significantly higher in AR group than in non-AR group even after 50,000 permutation tests (corrected p=0.018). In conclusion, these polymorphisms statistically significantly associated with acute renal allograft rejection may be considered as a risk factor of AR in Chinese renal transplantation recipients except for haplotype CACAG as a protective one.

Expression of soluble CD20 in peripheral blood of renal transplantation during reiection

Objective To study the relationship between the expression of sCD20 and the graft acute rejection,and the relationship between the level of sCD20 in peripheral blood and prognosis of the transplant kidney.Methods Fifty patients who had received renal transplantation from 2007 to 2010 were retrospectively reviewed.The expression of sCD20 in the blood was detected by enzyme linked immunosorbent assay (ELISA).Results The expression levels of sCD20 were higher in acute renal rejection group (1750.60±359.59) ng/L than those in non-rejection group (936.96 ± 181.71 ) ng/L before transplantation (P ＜0.05).After transplantation the expression levels of sCD20 were (2516.20 ±511.33) ng/L in acute renal rejection group and (988.40 ± 215.78 ) ng/L in non-rejection group ( P ＜ 0.05 ).Conclusion The expression of sCD20 in blood is correlated with clinical renal acute rejection and prognosis of the transplant kidney. Key words: Renal transplantation; CD20; Acute rejection

Serum soluble interleukin 2 receptor (sIL‐2R) as a marker of acute rejection in renal transplant children

The aim of the study was to evaluate whether or not serum levels of soluble interleukin 2 receptor (sIL-2R) predict acute rejection in pediatric recipients. We studied 51 pediatric renal transplant recipients divided into three groups: Group 1) Biopsy-proven cellular acute rejection (n = 19), Group 2) Graft dysfunction with histological diagnosis other than acute rejection (n = 8) and Group 3) Patients with stable graft function, no biopsy (n = 24). Serum samples for sIL-2R measurement by sandwich ELISA were obtained at the time of renal transplant and at the time of renal biopsy due to graft dysfunction (Groups 1 and 2) or at six months post-transplant in the case of Group 3. The mean ± s.e. serum values of sIL-2R were higher in patients during acute rejection (6539 ± 1802 pg/mL) compared to patients with other causes of graft dysfunction (2217 ± 256 pg/mL) or stable graft function at six months (2183 ± 283 pg/mL) (Kruskal-Wallis p = 0.004). When the sIL2-R levels at the time of transplant were compared to those at the time of biopsy (Groups 1 and 2) or at six months post-transplant in Group 3, there was no significant difference between baseline and biopsy in the acute rejection group (paired t-test = 0.07), whereas there was a significant reduction in Groups 2 and 3.

Metabonomics study of the acute graft rejection in rat renal transplantation using reversed-phase liquid chromatography and hydrophilic interaction chromatography coupled with mass spectrometry

Acute graft rejection is one of the most common and serious post complications in renal transplantation, noninvasive diagnosis of acute graft rejection is essential for reducing risk of surgery and timely treatment. In this study, a non-targeted metabonomics approach based on ultra performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (MS) is used to investigate the effect of acute graft rejection in rat renal transplantation on metabolism. To collect more metabolite information both hydrophilic interaction chromatography and reversed-phase liquid chromatography were used. Using the partial least squares-discriminant analysis, we found that the change of metabonome in a sham-operated group and a non-graft rejection group had a similar trend, while that of the acute graft rejection group was clearly different. Several discriminating metabolites of the acute graft rejection were identified, including creatinine, phosphatidyl-cholines, lyso-phosphatidylcholines, carnitine C16:0, free fatty acids and indoxyl sulfate etc. These discriminating metabolites suggested that acute graft rejection in renal transplantation can lead to the accumulation of creatinine in the body, and also the abnormal metabolism of phospholipids. These findings are useful to understand the mechanisms of the rejection, it also means that a UPLC-MS metabonomic approach is a suitable tool to investigate the metabolic abnormality in the acute graft rejection in renal transplantation.

Elevated urinary sVCAM-1, IL6, sIL6R and TNFR1 concentrations indicate acute kidney transplant rejection in the first 2 weeks after transplantation

We tested the hypothesis that increased urinary cytokine concentrations may indicate an acute kidney transplant rejection. Eight patients with an early rejection in their protocol biopsy about 14days after transplantation (group A), 9 patients with a biopsy proven rejection 2–3months after transplantation (group B) and 18 patients without acute rejection in their protocol biopsies both at 14days and 3months (group C, represents the control group) were chosen for this study. At the time of biopsy, the mean urinary concentration of interleukin 6 (IL6), soluble IL6 receptor (sIL6R), tumor necrosis factor receptor 1 (TNFR1), and soluble vascular cell adhesion molecule −1 (sVCAM-1) were significantly higher in patients with an early acute transplant rejection, i.e. in group A compared to patients in the control group (p<0.01). Additionally we found already 14days after transplantation significantly higher concentrations of urinary sIL6R and sVCAM-1 in group B patients who suffered of late acute rejection compared to patients with no acute rejection (group C, p<0.05). No significant correlation could be shown for interleukin 1 receptor antagonist (IL1ra), TNF, and TNFR2. In conclusion, elevated urinary concentrations of IL6, sIL6R, TNFR1 and sVCAM-1 clearly indicate an early acute transplant rejection. Especially sVCAM-1 may also serve as an early marker of an upcoming late rejection. However, further studies are warranted to verify the value of individual cytokine profiles to predict acute rejection episodes.

IL-17 in the early diagnosis of acute renal allograft rejection in mice.

To investigate the expression of T helper (Th) 17 cells and the related interleukin 17 (IL-17) in acute renal allograft rejection in mice and its significance. We established a mouse renal allograft model, in which mice were randomly divided into a renal isograft group and an acute renal allograft rejection group. Three and 7 d after the transplantation, the serum interferon (IFN)-γ and IL-17 levels in the mice were determined by enzyme-linked immunosorbent assay, the percentage of Th1 and Th17 cells in the total kidney-infiltrating lymphocytes was investigated by flow cytometry, and the transplanted kidney species were given routine pathological examination after fixation with 10% formalin. Compared with the isograft group, the allograft mice showed a significantly higher content of IL-17 (P<0.05) but not IFN-γ in the serum 3 d after transplantation, and showed significantly higher serum IL-17 and IFN-γ contents 7 d after transplantation (P<0.05). Also, compared with the isograft group, the allograft mice exhibited significantly higher percentage of Th1 and Th17 cells on both day 3 and day 7 (P<0.05). In the allograft group, the contents of serum IFN-γ and IL-17 and the percentage of Th1 and Th17 cells were significantly higher on day 7 than on day 3 (P<0.05). Routine pathological examination indicated that, as time passed, the allograft mice showed gradually stronger rejection responses. Th17 cells might play an important role in the development of acute renal allograft rejection, and IL-17 can be used as an early indicator of acute rejection.

Rapamycin combined with donor immature dendritic cells promotes liver allograft survival in association with CD4+CD25+Foxp3+ regulatory T cell expansion

To determine whether donor immature dendritic cells (imDCs) combined with a short postoperative course of rapamycin (Rapa) has the ability to expand the CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells and prolong liver allograft survival. Orthotopic liver transplantation (OLT) was performed from Lewis rats to Brown Norway recipients. Three days before transplantation, animals were injected intravenously with 2 × 10(6) donor bone marrow-derived imDCs. Recipient rats (the combined treated group) also received Rapa for 7 d after liver transplantation. Additional groups received either imDCs alone, Rapa alone, or saline alone. Every six recipients from each group were killed at 14 days, 28 days after OLT. The changes of CD4(+) CD25(+) Foxp3(+) Treg cells in peripheral blood and spleen, histological changes of liver grafts, and serum cytokine levels were investigated. The other six recipients were left in each group to observe the animal survival. Donor imDCs followed by a short postoperative course of Rapa induced long-term allograft survival. The percentage of CD4(+) CD25(+) Foxp3(+) Treg cells in CD4(+) T cells in the combination treatment group were significantly higher compared with the acute rejection group. Moreover, within the CD4(+) CD25(+) T cell population the combination treatment recipients maintained a higher incidence of Foxp3(+) T cells compared with the other groups. Despite the lower serum levels of interleukin (IL)-2, IL-12, and interferon-γ in the combined treated group, the cytokine levels in the combined treated group at 7 days after OLT was nearly twice that at 3 days after OLT but decreased significantly compared with the other groups at 28 days after OLT. Serum IL-10 level in the combined treated group was higher than the other groups. A single imDC infusion followed by a short postoperative course of Rapa prolongs liver allograft survival and enhances the expansion of Treg cells. This optimal protocol may be a promising administration protocol for the peritransplant tolerance induction.

Copy number variation in CCL3L1 gene is associated with susceptibility to acute rejection in patients after liver transplantation

Copy number variation (CNV) in gene was a novel type of genetic diversity in human that affect the pathogenesis, progress, and prognosis of disease. The aim of this study was to determine the associations between CNV in CCL3L1 gene and the rejection risk in liver-transplant recipients. The 266 Han-Chinese patients and 135 volunteers were enrolled in this study. Genomic DNA and mRNA samples were obtained from the whole peripheral blood; a quantitative real-time PCR-based assay was carried out to determine the copy number of CCL3L1, and real-time PCR was carried out to calculate the CCL3L1/CCL3 mRNA ratio. The CNV distributions in patients and health controls had no significant differences. Copy number in acute rejection group (AR) shifted to higher number compared with non-acute rejection group (4.74±1.87 vs. 3.88±2.13, p=0.017). Moreover, patients with higher CCL3L1 copies (≥3 copies) had a significantly higher rejection risk than patients lower copies CCL3L1 (OR=3.85, 95% CI, 1.14-13.04; p=0.021). No association was found between CNV and rejection grades. In conclusion, liver transplant recipients with high copy number of CCL3L1 gene had a significant higher risk of AR. CNV might be a novel genetic diversity that correlated with allograft rejection.

Advantages of Promoting Interleukin-10 by Silence of Histone Deacetylase 11 in Inducing Tolerance in Orthotopic Liver Transplantation in Rats

Aims The aims of this study were to study the role of histone deacetylase 11 (HDAC11) in tolerance induction in orthotopic liver transplantation (OLT) in rats and to assess the advantages of gene therapy over the immunosuppressant FK506. Methods Recipients were assigned to an acute rejection group (AcR; group I), an FK506 intervention group (group II), and a tolerance group (group III). Acute rejection (AcR) was graded by the Banff scheme and we examined postoperative survival. The messenger RNA (mRNA) and protein expressions of histone deacetylase 11 (HDAC11) and interleukin (IL) 10 in liver tissue were detected using real-time polymerase chain reaction (PCR) and Western blots, respectively. Plasma levels of tumor necrosis factor (TNF)-α, IL-2, and IL-10 were measured using enzyme-linked immunosorbent Assays. Results Group I displayed severe, Group II had less, and Group III had no evidence of AR. The survivals among Group III were longer than those in Group I and Group II. IL-10 expression was promoted by HDAC11-shRNA at 7 days after OLT. Serum IL-2 and TNF-α levels were significantly lower among Group III compared with Groups I and II, whereas IL-10 showed the opposite result. Conclusions Silence of HDAC11 promotes IL-10 expression and leads to tolerance following OLT in rats. Thus HDAC11 is a promising target for gene therapy to induce tolerance with advantages over immunosuppressive drugs.

Elevation of Antidonor Immunoglobulin M Levels Precedes Acute Lung Transplant Rejection

No useful noninvasive biomarker exists for diagnosing acute rejection after lung transplantation (LTx). In this study, antidonor T-cell antibodies were monitored daily in living-donor lobar LTx recipients to determine whether they are correlated with the onset of steroid-responsive typical acute rejection. Ten nonsensitized patients who underwent bilateral living-donor lobar LTxs donated from 2 persons were analyzed. In 5 patients, unilateral acute rejection developed during the first 14 days after LTx and responded to subsequent pulse steroid therapies. The other patients experienced no rejection episodes during the period. Immunoreactivity against T cells from each lobe of the donors was monitored daily by detecting antidonor immunoglobulin (Ig) M and IgG using flow cytometry crossmatching for 14 days after LTx. There was a remarkable increase in IgM levels against rejected grafts around the onset of acute rejection, but this increase was not observed against nonrejected grafts. The mean IgM levels against rejected grafts 14 days after transplantation was significantly higher than that against nonrejected grafts in the acute rejection group (p = 0.009) and the no rejection group (p = 0.010). In the acute rejection group, the IgM level against rejected grafts became significantly higher than those against nonrejected grafts 2 days before the clinical onset of acute rejection. These trends were statistically marginal or not detected for IgG levels. Significant immunoreactivity of IgM, but not IgG, preceded the clinical onset of acute rejection. Antidonor IgM monitoring can contribute to the early detection of steroid-responsive acute rejection.

Expression of glucocorticoid induced tumor necrosis factor receptor ligand during acute rejection after rat liver transplantation

Objective To investigate te changes of glucocorticoid induced tumor necrosis factor receptor ligand (GITRL) in hepatic allograft rejection. Methods Liver transplantation from Lewis rats (n = 5 ) to Brown Norway (BN) rats was performed by Kamada' s two-cuff technique as acute rejection group. Liver transplantation from BN to BN rats ( n = 5 ) was performed as tolerance group. Recipients were sacrificed at 24th h postoperation. Blood samples were collected and grafts were harvested, then Kupffer cells were isolated. GITRL and tumor necrosis factor (TNF)-α protein expression in the hver was tested by immunohistochemistry, and the GITRL expression in Kupffer cells by immunocytochemistry. Enzyme linked immunosorbent assay (ELISA) was employed to detect the changes of TNF-α protein in the serum and supernatant. The staining intensity was analyzed by Image-Pro Plus 6. 0 image analysis software. Results At 24th h postoperation, the liver GITRL expression levels in tolerance and rejection groups were 0. 113 ± 0. 007 and 0. 270 ±0. 018, respectively (P ＜0. 05). The TNF-α expression levels in the liver in tolerance and rejection groups were 0. 114 ± 0. 004 and 0. 141 ± 0. 005 respectively ( P ＜ 0.05 ). The GITRL expression levels in Kupffer cells in tolerance and rejection groups were 0. 206 ±0. 017 and 0. 337 ±0. 018 respectively (P ＜0. 05 ). As compared with tolerance group (68. 66 ±21.12) ng/L, TNF-α protein expression levels were up-regulated in the supernatant of rejection group ( 178.33 ± 29. 39 ) ng/L ( P ＜ 0. 05 ).Conclusion The expression of GITRL in the liver and Kupffer cells was increased in the early stage of rejection, and monitoring and interfering GITRL may be useful for the early diagnosis and management of an acute rejection in liver transplantation. Key words: GITRL; Liver transplantation; Acute rejection; Kupffer cells

Quantitative Evaluation of Acute Renal Transplant Dysfunction with Low-Dose Three-dimensional MR Renography

To assess prospectively the ability of quantitative low-dose three-dimensional magnetic resonance (MR) renography to help identify the cause of acute graft dysfunction. This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained. Between December 2001 and May 2009, sixty patients with transplanted kidneys (41 men and 19 women; mean age, 49 years; age range, 22-71 years) were included. Thirty-one patients had normal function and 29 had acute dysfunction due to acute rejection (n = 12), acute tubular necrosis (ATN) (n = 8), chronic rejection (n = 6), or drug toxicity (n = 3). MR renography was performed at 1.5 T with three-dimensional gradient-echo imaging. With use of a multicompartment renal model, the glomerular filtration rate (GFR) and the mean transit time (MTT) of the tracer for the vascular compartment (MTT(A)), the tubular compartment (MTT(T)), and the collecting system compartment (MTT(C)) were calculated. Also derived was MTT for the whole kidney (MTT(K) = MTT(A) + MTT(T) + MTT(C)) and fractional MTT of each compartment (MTT(A/K) = MTT(A)/MTT(K), MTT(T/K) = MTT(T)/MTT(K), MTT(C/K) = MTT(C)/MTT(K)). These parameters were compared in patients in the different study groups. Statistical analysis was performed by using analysis of covariance. There were significant differences in GFR and MTT(K) between the acute dysfunction group (36.4 mL/min ± 20.8 [standard deviation] and 177.1 seconds ± 46.8, respectively) and the normal function group (65.9 mL/min ± 27.6 and 140.5 seconds ± 51.8, respectively) (P < .001 and P = .004). The MTT(A/K) was significantly higher in the acute rejection group (mean, 12.7% ± 2.9) than in the normal function group (mean, 8.3% ± 2.2; P < .001) or in the ATN group (mean, 7.1% ± 1.4; P < .001). The MTT(T/K) was significantly higher in the ATN group (mean, 83.2% ± 9.2) than in the normal function group (mean, 72.4% ± 10.2; P = .031) or in the acute rejection group (mean, 69.2% ± 6.1; P = .003). Low-dose MR renography analyzed by using a multicompartmental tracer kinetic renal model may help to differentiate noninvasively between acute rejection and ATN after kidney transplantation.

Soluble Human Leukocyte Antigen-G in Pediatric Renal Transplantation

Soluble Human Leukocyte Antigen-G in Pediatric Renal Transplantation

Detection of autosomal dominant polycystic kidney disease by NMR spectroscopic fingerprinting of urine

Autosomal dominant polycystic kidney disease (ADPKD) is a frequent cause of kidney failure; however, urinary biomarkers for the disease are lacking. In a step towards identifying such markers, we used multidimensional-multinuclear nuclear magnetic resonance (NMR) spectroscopy with support vector machine-based classification and analyzed urine specimens of 54 patients with ADPKD and slightly reduced estimated glomerular filtration rates. Within this cohort, 35 received medication for arterial hypertension and 19 did not. The results were compared with NMR profiles of 46 healthy volunteers, 10 ADPKD patients on hemodialysis with residual renal function, 16 kidney transplant patients, and 52 type 2 diabetic patients with chronic kidney disease. Based on the average of 51 out of 701 NMR features, we could reliably discriminate ADPKD patients with moderately advanced disease from ADPKD patients with end-stage renal disease, patients with chronic kidney disease of other etiologies, and healthy probands with an accuracy of >80%. Of the 35 patients with ADPKD receiving medication for hypertension, most showed increased excretion of proteins and also methanol. In contrast, elevated urinary methanol was not found in any of the control and other patient groups. Thus, we found that NMR fingerprinting of urine differentiates ADPKD from several other kidney diseases and individuals with normal kidney function. The diagnostic and prognostic potential of these profiles requires further evaluation.