BackgroundContribution of model for end-stage liver disease incorporating with serum sodium (MELD-Na) score in predicting acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is yet to be identified. This study assessed the prognostic value of MELD-Na score for the development of AKI following OLT.

MethodsPreoperative and surgery-related variables of 321 adult end-stage liver disease patients who underwent OLT in Fuzhou General Hospital were collected. Postoperative AKI was defined and staged in accordance with the clinical practice guidelines developed by Kidney Disease: Improving Global Outcomes. Univariate and multivariate analysis was performed to determine the risk factors for AKI following OLT. The discriminating power of MELD/MELD-Na score on AKI outcome was evaluated by receiver operating characteristic (ROC) curve. Spearman's correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of AKI.

ResultsThe prevalence of AKI following OLT was in 206 out of 321 patients (64.2%). Three risk factors for AKI post-OLT were presented, preoperative calculated MELD score (odds ratio [OR] = 1.048, P = 0.021), intraoperative volume of red cell suspension transfusion (OR = 1.001, P = 0.002), and preoperative liver cirrhosis (OR = 2.015, P = 0.012). Two areas under ROC curve (AUCs) of MELD/MELD-Na score predicting AKI were 0.688 and 0.672, respectively; the difference between two AUCs was not significant (Z = 1.952, P = 0.051). The Spearman's correlation coefficients between MELD/MELD-Na score and the severity levels of AKI were 0.406 and 0.385 (P = 0.001, 0.001), respectively.

ConclusionsWe demonstrated that preoperative MELD score, intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were risk factors for AKI following OLT. Furthermore, we preliminarily validated that MELD score seemed to have a stronger power discriminating AKI post-OLT than that of novel MELD-Na score.

Acute Kidney Injury ; blood ; etiology ; pathology ; Adult ; End Stage Liver Disease ; blood ; etiology ; pathology ; Female ; Humans ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Retrospective Studies ; Sodium ; blood

OBJECTIVETo study the clinical and histopathologic features of post-transplant kidney biopsy tissues from pediatric C-III donors.

METHODSThe clinical and pathologic features of 20 cases (22 case-times) of renal transplant biopsies from pediatric cadaveric donors were analyzed by light microscopy and immunohistochemistry according to the Banff system of working classification of renal allograft pathology. Biopsies were compared to those from adult C-III donors and adult cadaveric donors.

RESULTSSixteen cases (72.7%) showed renal allograft drug toxicity damage by Tacrolimus, seven cases (31.8%) showed degeneration and necrosis of renal tubular epithelial cells, four cases (18.2%) showed T cell-mediated acute rejection and six cases (27.3%) showed renal interstitial inflammation. There were two cases (9.1%) of renal dysplasia and one case (4.5%) of renal infarction. There was insufficient evidence for diagnosis of renal allograft nephropathy. Compared to post-transplant kidney from adult C-III donors, the proportion of drug toxicity damage was higher (P<0.05). Compared to post-transplant kidney from adult cadavers, the proportions of drug toxicity damage, degeneration and necrosis of renal tubular epithelial cells were higher (P<0.05) while the proportion of acute rejection was lower (P<0.05).

CONCLUSIONSThe pathologic changes in the post-transplant kidneys from pediatric donors are different from those from adult donors. Optimal long-term outcome can be accomplished by effective treatment based on timely or procedural biopsy.

Adult ; Age Factors ; Biopsy ; Cadaver ; Child ; Graft Rejection ; pathology ; Humans ; Immunohistochemistry ; Immunosuppressive Agents ; adverse effects ; Infarction ; pathology ; Kidney ; blood supply ; drug effects ; pathology ; Kidney Transplantation ; Kidney Tubules ; drug effects ; pathology ; Necrosis ; Tacrolimus ; adverse effects ; Transplantation, Homologous ; Treatment Outcome

BACKGROUND: Angiotensin II type 1 receptor (AT1R) is responsible for cardiovascular effects mediated by angiotensin II. This study aimed to investigate the impact of antibodies directed against AT1R (anti-AT1R) in renal allograft rejection. METHODS: We evaluated 53 patients who had biopsy-proven rejection including antibody-mediated rejection (AMR) (N=22), T-cell-mediated rejection (TCMR) (N=29), and mixed AMR and TCMR (N=2). Donor specific HLA antibodies (DSA) and anti-AT1Rs were simultaneously determined. RESULTS: Anti-AT1Rs were detected in 9.4% (5/53) of rejection patients (one with acute AMR, two with chronic active AMR, one with acute TCMR, and one with mixed acute AMR & TCMR). HLA antibodies and DSA were detected in 75.5% (40/53) and 49.1% (26/53) of patients, respectively. There was no significant difference in transplant characteristics between anti-AT1R(+) and anti-AT1R(-) patients except for the association of HLA class-I DSA(+) and anti-AT1R(+). Four of five anti-AT1R(+) patients had DSA and were also found to have AMR. A single anti-AT1R(+)/DSA(-) patient developed acute TCMR. Detection rates of DSA, HLA antibodies, or anti-AT1R were not different between AMR and TCMR. However, DSA(+)/anti-AT1R(+) was more frequently found in AMR than in TCMR (P=0.036). Patients with anti-AT1R showed a greater tendency to develop high-grade rejection as Banff IIA/IIB or AMR. CONCLUSIONS: The presence of anti-AT1R was significantly associated with HLA class-I DSA in renal allograft rejection patients. Both anti-AT1R and DSA positivity was associated with AMR in patients with renal allograft rejection.
Adult ; Antibodies/blood ; Female ; Graft Rejection/*etiology ; HLA Antigens/immunology ; Humans ; Kidney/pathology ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Receptor, Angiotensin, Type 1/*immunology ; Tissue Donors ; Transplantation, Homologous

OBJECTIVETo investigate the pathological and immunological changes of renal grafts in recipients experiencing graft rejection.

METHODSThe clinicopathologic data of 56 renal needle biopsy samples obtained from renal transplant recipients were analyzed retrospectively. The specimens were classified histopathologically according to the Banff 2009 classification system and analyzed by immunohistochemical labeling and immunofluorescence.

RESULTSIn the 56 recipients, 1 (1.79%) experienced hyperacute rejection, 8 (14.29%) had suspected acute rejection, 12 (21.43%) developed acute T-cell rejection, 6 (10.71%) had acute antibody-mediated rejection, 2 (3.57%) had acute T-cell rejection with acute antibody-mediated rejection, 12 (21.43%) had chronic active T cell-mediated rejection, 2 (3.57%) had chronic active antibody-mediated rejection, 2 (3.57%) had chronic active T cell-mediated rejection with antibody-mediated rejection, 8 (14.29%) had non-specific interstitial fibrosis and tubular atrophy, and 3 (5.36%) had normal graft function. The expression levels of immune markers CD3, CD4, CD8, CD20, GrB and perforin differed with the types of T cell-mediated graft rejection, and the positivity and expression levels of these markers tended to increased with the severity of graft rejection. The expression of C4d was positive in all cases with antibody-mediated graft rejection.

CONCLUSIONSThe pathological characteristics of the renal biopsy specimens and expression levels of the immune markers allow timely and accurate evaluation of graft rejection type to provide a reliable pathological and etiological basis for clinical treatment and prognostic assessment.

Adolescent ; Adult ; Aged ; Female ; Graft Rejection ; immunology ; pathology ; Graft Survival ; Humans ; Kidney ; immunology ; pathology ; Kidney Transplantation ; adverse effects ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Since the introduction of pancreas transplantation more than 40 years ago, surgical techniques and immunosuppressive regiments have improved and both have contributed to increase the number and success rate of this procedure. However, graft survival corresponds to early diagnosis of organ-related complications. Thus, knowledge of the transplantation procedure and postoperative image anatomy are basic requirements for radiologists. In this article, we demonstrate the imaging spectrum of pancreas transplantation with enteric exocrine drainage.
Adult ; Anastomosis, Surgical/methods ; Diagnostic Imaging/methods ; Drainage/methods ; Female ; Graft Rejection/pathology ; Graft Survival ; Humans ; Iliac Artery/radiography/surgery ; Immunosuppressive Agents ; Kidney Transplantation ; Male ; *Medical Illustration ; Mesenteric Artery, Superior/radiography/surgery ; Middle Aged ; Pancreas/*blood supply/radiography ; Pancreas Transplantation/adverse effects/*methods ; Pancreatitis, Graft/etiology ; Portal Vein/radiography/surgery ; Postoperative Complications/radiography ; Postoperative Hemorrhage/etiology ; Survival Rate

BK virus-associated nephropathy (BKVAN) is one of the major causes of allograft dysfunction in kidney transplant (KT) patients. We compared BKVAN combined with acute rejection (BKVAN/AR) with BKVAN alone in KT patients. We retrospectively analyzed biopsy-proven BKVAN in KT patients from 2000 to 2011 at Seoul National University Hospital. Among 414 biopsies from 951 patients, biopsy-proven BKVAN was found in 14 patients. Nine patients had BKVAN alone, while 5 patients had both BKVAN and acute cellular rejection. BKVAN in the BKVAN alone group was detected later than in BKVAN/AR group (21.77 vs 6.39 months after transplantation, P=0.03). Serum creatinine at diagnosis was similar (2.09 vs 2.00 mg/dL). Histological grade was more advanced in the BKVAN/AR group (P=0.034). Serum load of BKV, dose of immunosuppressants, and tacrolimus level showed a higher tendency in the BKVAN alone group; however it was not statistically significant. After anti-rejection therapy, immunosuppression was reduced in the BKVAN/AR group. Renal functional deterioration over 1 yr after BKVAN diagnosis was similar between the two groups (P=0.665). These findings suggest that the prognosis of BKVAN/AR after anti-rejection therapy followed by anti-BKV therapy might be similar to that of BKVAN alone after anti-BKV therapy.
Acute Disease ; Adult ; Antiviral Agents/therapeutic use ; BK Virus/*physiology ; Creatinine/blood ; Female ; *Graft Rejection/diagnosis/virology ; Humans ; Immunosuppressive Agents/administration & dosage ; Kidney/*virology ; Kidney Diseases/pathology/surgery/*virology ; *Kidney Transplantation ; Male ; Middle Aged ; Polyomavirus Infections/drug therapy/*etiology/pathology ; Retrospective Studies ; Tacrolimus/administration & dosage ; Time Factors ; Transplantation, Homologous/adverse effects ; Tumor Virus Infections/drug therapy/*etiology/pathology

OBJECTIVETo investigate the inhibitory effects of a novel histone deacetylases inhibitor FK228 on human colon cancer HCT-116 cells in vitro and in vivo, and evaluate its toxicity and side effects.

METHODSThe in vitro growth inhibitions of HCT-116 cells by different concentrations of FK228 and 5-Fu for 24, 48 and 72 h were assessed by CCK-8 assay. BALB/c nude mouse models of tumor xenografts were prepared by subcutaneous implantation of tumor tissue, and 4 mg/kg FK228 and 50 mg/kg 5-Fu were i.p. injected, respectively. The inhibitory effects on tumor growth, hematology, and liver and kidney function were evaluated.

RESULTSCCK-8 assay indicated that FK228 had an obvious growth inhibitory effect on HCT-116 cells in a dose- and time-dependent manner. The IC50 of FK228 in HCT-116 cells was 12.05 ng/ml for 48 h, while the IC50 of 5-Fu was 18.92 µg/ml. At 20 days after FK228 and 5-Fu treatment, the tumor volume of the FK228 group was (139.71 ± 44.54)mm(3), significantly lower than that of the 5-Fu group [(282.28 ± 58.81)mm(3)] and that of the model group [(520.65 ± 39.73)mm(3), P < 0.01 for both]. The average tumor weight was (0.07 ± 0.02)g in the FK228 group, significantly lower than that of the 5-Fu group [(0.20 ± 0.08)g, P < 0.01]. The tumor growth inhibition rate of the FK228 group was 73.2%, significantly higher than that of the 5-Fu group (45.8%, P < 0.01). The ALT levels of the FK228 and 5-Fu groups were significantly higher than that of the model group (P < 0.01). The BUN of 5-Fu group was significantly higher than that of the model group (P < 0.01), but the BUN of FK228 group was not significantly different from that of the blank and control groups (P > 0.05 for both). Routine blood test showed that WBC, RBC, Hb and PLT of the 5-Fu group were significantly lower than those of the model group (P < 0.05 for all), but only WBC of the FK228 group was significantly lower than that of the model group (P < 0.05). The pathological examination using HE staining revealed that in the FK228 group, there were fibrosis and inflammatory cell infiltration in the liver tissue, and mild edema of the renal tubules in the kidney. However, in the 5-Fu group there were extensive hepatocyte edema and necrosis in the liver, and evident deformation and necrosis of glomeruli and tubules, and tubular wall thinning in the kidney.

CONCLUSIONSThe results of this study indicate that FK228 can more effectively than 5-Fu inhibit the growth of HCT-116 cells in vitro and vivo, and without obvious toxic effect on the kidney and hematology. Its clinical value in colon cancer treatment deserves further investigation.

Alanine Transaminase ; blood ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; adverse effects ; pharmacology ; Antimetabolites, Antineoplastic ; pharmacology ; Blood Urea Nitrogen ; Cell Proliferation ; drug effects ; Depsipeptides ; administration & dosage ; adverse effects ; pharmacology ; Dose-Response Relationship, Drug ; Fluorouracil ; pharmacology ; HCT116 Cells ; Hematologic Tests ; Histone Deacetylase Inhibitors ; administration & dosage ; adverse effects ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Kidney ; pathology ; Liver ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Random Allocation ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

Antineoplastic Agents ; adverse effects ; Child ; Child, Preschool ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Kidney Diseases ; etiology ; pathology ; therapy ; Kidney Neoplasms ; etiology ; pathology ; therapy ; Neoplasms ; complications ; therapy ; Paraneoplastic Syndromes ; etiology ; pathology ; therapy ; Radiotherapy ; adverse effects ; Risk Factors ; Tumor Lysis Syndrome ; etiology ; pathology ; therapy

OBJECTIVETo study the clinical and histopathologic features, diagnosis, pathogenesis and therapy of post-transplant lymphoproliferative disorders (PTLD).

METHODSThe clinical and pathologic features of 15 cases of PTLD were retrospectively analyzed by light microscopy, immunohistochemistry and in-situ hybridization, according to the updated 2008 WHO classification of tumors of hematopoietic and lymphoid tissues.

RESULTSAmongst the 15 cases studied, 14 cases had received allogenic hematopoietic stem cell transplantation (AHSCT) and 1 case had received renal transplantation. There were altogether 12 males and 3 females. The male-to-female ratio was 4:1. The mean age was 30.4 years and the median age was 31 years (range from 9 to 60 years). PTLD developed 1.5 to 132 months after transplantation (median 13.0 months). The mean age of the 14 patients with AHSCT was 28.3 years (range from 9 to 45 years) and PTLD developed 1.5 to 19 months after transplantation (mean 4.5 months). Major clinical presentation included fever and lymphadenopathy. Twelve cases involved mainly lymph nodes and the remaining 3 cases involved tonsils, stomach and small intestine, respectively. The histologic types in 4 cases represented early lesions, including plasmacytic hyperplasia (n = 1) and infectious mononucleosis-like PTLD (n = 3). Seven cases were polymorphic PTLD, with 4 cases containing a predominance of large cells. Graft-versus-host disease was also seen in the case of small intestinal involvement. Four cases were monomorphic PTLD, 3 of which were diffuse large B-cell lymphoma, 1 was plasmablastic lymphoma and 1 was a mixture of monomorphic and polymorphic PTLD. Foci of necrosis were seen in 5 cases. The proliferating index of Ki-67 was high. The positive rate of EBV-encoded RNA in AHSCT was 92.9%. The duration of PTLD onset was shorter in EBV-positive cases (range from 1.5 to 7 months) than EBV-negative cases (range from 19 and 132 months). Some cases were treated by reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab. The duration of follow-up in 14 patients ranged from 0 to 8 months. Five of the patients died of the disease.

CONCLUSIONSThe diagnosis of PTLD relies on morphologic examination and immunohistochemistry. Most of them are of B-cell origin. EBV plays an important role in the pathogenesis of PTLD. The duration of disease onset is shorter in EBV-positive cases. PTLD in AHSCT cases occurs in younger age group, with shorter duration of onset, as compared to solid organ transplantation. The prognosis of PTLD is poor. The modalities of treatment include reduction of immunosuppression, antiviral agents or anti-CD20 monoclonal antibody Rituximab.

ADP-ribosyl Cyclase 1 ; metabolism ; Adolescent ; Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antigens, CD20 ; metabolism ; Antineoplastic Agents ; therapeutic use ; Child ; Epstein-Barr Virus Infections ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunosuppressive Agents ; therapeutic use ; Ki-1 Antigen ; metabolism ; Kidney Transplantation ; adverse effects ; Leukemia ; therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; etiology ; pathology ; virology ; Lymphoproliferative Disorders ; drug therapy ; etiology ; pathology ; virology ; Male ; Middle Aged ; RNA, Viral ; metabolism ; Retrospective Studies ; Rituximab ; Young Adult

The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injury scores using the Banff classification. The average numbers of infiltrating Treg and Th17 cells were 11.6 +/- 12.2 cells/mm2 and 5.6 +/- 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 +/- 8.2. The Treg/Th17 ratio was significantly associated with allograft function (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular injury (P < 0.05, all parameters). In separate analyses of the number of infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly associated with allograft function and the severity of tissue injury. By contrast, Treg cell infiltration was not significantly associated with allograft dysfunction or the severity of tissue injury. The results of this study show that higher infiltration of Th17 cell compared with Treg cell is significantly associated with the severity of allograft dysfunction and tissue injury.
Acute Disease ; Creatinine/metabolism ; Forkhead Transcription Factors/metabolism ; Graft Rejection/*etiology/pathology ; Humans ; Immunoenzyme Techniques ; Interleukin-17/*metabolism ; Kidney Transplantation/*adverse effects ; Retrospective Studies ; T-Lymphocytes, Regulatory/*immunology/pathology ; Th17 Cells/*immunology/pathology ; Transplantation, Homologous