Gene expression profiling of sepsis-associated acute kidney injury.

Sepsis accounts for more than 50% of all acute kidney injury (AKI) cases, and the combination of sepsis and AKI increases the risk of mortality from sepsis alone. However, to the best of our knowledge, the specific mechanism by which sepsis causes AKI has not yet been fully elucidated, and there is no targeted therapy for sepsis-associated AKI (SA-AKI). The present study investigated gene expression profiles using RNA sequencing (RNA-Seq) and bioinformatics analyses to assess the function of differentially expressed genes (DEGs) and the molecular mechanisms relevant to the prognosis of SA-AKI. From the bioinformatics analysis, 2,256 downregulated and 3,146 upregulated genes were identified (false discovery rate <0.1 and fold-change >2). Gene Ontology analysis revealed that the genes were enriched in cellular metabolic processes, cell death and apoptosis. The enriched transcription factors were v-rel reticuloendotheliosis viral oncogene homolog A and signaling transducer and activator of transcription 3. The enriched microRNAs (miRNAs or miRs) among the DEGs were miR-30e, miR-181a, miR-340, miR-466d and miR-466l. Furthermore, the enriched pathways included toll-like receptor signaling, nod-like receptor signaling and the Janus kinase/STAT signaling pathway. In conclusion, the present study identified certain prognosis-related genes, transcription factors, miRNAs and pathways by analyzing gene expression profiles of SA-AKI using RNA-Seq, which provides some basis for future experimental studies.

Preoperative Serum Fibrinogen is Associated With Acute Kidney Injury after Cardiac Valve Replacement Surgery.

Acute kidney injury (AKI) after open cardiac surgery is associated with a longer hospital stay and higher risk of mortality. We aimed to explore the association between preoperative serum fibrinogen level and risk of postoperative AKI in patients with open cardiac surgery. 3459 patients who underwent cardiac valve replacement surgery from January 2011 to September 2015 were recruited. The primary outcome was AKI, defined as AKI stage-1 or higher based on the Kidney Disease: Improving Global Outcomes (KDIGO) Guidelines. Synthetic Minority Oversampling Technique (SMOTE) was used to subsample minority groups to eliminate classification bias. 510 (14.74%) patients developed postoperative AKI. Serum fibrinogen was independently associated with AKI (OR = 1.211, 95% CI 1.080 to 1.358, p = 0.001) after adjustment of covariates. The receiver operator characteristic (ROC) curve for the outcome of AKI, after the addition of serum fibrinogen, had a c-statistic increasing from 0.72 to 0.73 (p < 0.001). This translated to a substantially improved AKI risk classification with a net reclassification index of 0.178 (p < 0.001). After SMOTE subsampling, serum fibrinogen was still independently associated with AKI grade 1 or higher (OR = 1.212, 95% CI 1.1089 to 1.347, p = 0.003). Preoperative serum fibrinogen levels were associated with the risk of postoperative AKI after cardiac valve replacement surgery.

Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft Injury.

Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers. CD68+/α-SMA+ cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and α-SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of α-SMA+ myofibroblasts in renal allografts originated from recipient bone marrow-derived macrophages. Knockout of Smad3 protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in Smad3-knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow-derived M2-type macrophages to myofibroblasts in the renal allograft is regulated via a Smad3-dependent mechanism.

Mycophenolate Mofetil Combined With Prednisone Versus Full-Dose Prednisone in IgA Nephropathy With Active Proliferative Lesions: A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that patients with immunoglobulin A nephropathy (IgAN) with active proliferative lesions show a good response to immunosuppressive treatment. STUDY DESIGN: Multicenter, prospective, randomized, controlled trial. SETTING & PARTICIPANTS: 176 patients with IgAN with active proliferative lesions (cellular and fibrocellular crescents, endocapillary hypercellularity, or necrosis), proteinuria with protein excretion ≥ 1.0g/24h, and estimated glomerular filtration rate > 30mL/min/1.73m2. INTERVENTION: Mycophenolate mofetil (MMF) group: MMF, 1.5g/d, for 6 months and prednisone, 0.4 to 0.6mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months; prednisone group: prednisone, 0.8 to 1.0mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months. All patients were followed up for another 6 months. OUTCOMES: The primary end point was complete remission rate at 6 and 12 months. RESULTS: At baseline, median estimated glomerular filtration rates were 90.2 and 94.3mL/min/1.73m2 and mean proteinuria was protein excretion of 2.37 and 2.47g/24h in the MMF and prednisone groups, respectively. At 6 months, complete remission rates were 37% (32 of 86 patients) and 38% (33 of 88 patients); the between-group difference was not statistically significant (P=0.9). At 12 months, complete remission rates were 48% (35 of 73 patients) and 53% (38 of 72 patients) in the MMF and prednisone groups, respectively; the between-group difference was not statistically significant (P=0.6). Incidences of Cushing syndrome and newly diagnosed diabetes mellitus were lower in the MMF group than in the prednisone group. LIMITATIONS: Not all participants were treated with renin-angiotensin system blockers, relatively short follow-up. CONCLUSIONS: MMF plus prednisone versus full-dose prednisone did not differ in reducing proteinuria, but patients treated with the former had fewer adverse events in patients with IgAN with active proliferative lesions.

Biomarkers for Early Diagnosis of Acute Kidney Injury: Current Progress and Clinical Prospects.

Acute kidney injury (AKI) is one of the most common complications in critically ill patients, resulting in high morbidity and mortality. AKI usually occurs after major surgery, severe infection or drug-induced nephrotoxicity and is associated with prolonged hospital stays, increased costs and adverse clinical outcomes. The diagnosis of AKI is currently based on decreased glomerular filtration rate (GFR) and urine output, and increased serum creatinine. Novel biomarkers are required for early identification of patients with AKI to allow timely therapy and improve patient outcomes. With the advent of proteomics and genomics techniques, a vast array of biomarkers are now available in clinical practice.

Effect of uric acid-lowering therapy on blood pressure: systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to determine if uric acid-lowering therapy is associated with a decrease in blood pressure (BP) and serum creatinine levels. MATERIALS AND METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 29 June 2016, with keywords: uric-acid-lowering therapy, allopurinol, febuxostat, uricosuric, and BP. Only randomized controlled trials were included. The primary outcomes were reduction in systolic BP (SBP) and diastolic BP (DBP), and secondary was reduction in serum creatinine level. RESULTS: Patients treated with allopurinol had greater reduction in SBP (standardized difference in means [SDM] = 0.321, 95% confidence interval [CI]: 0.145-0.497, p < 0.001), DBP (SDM = 0.260, 95% CI: 0.102 to 0.417, p = 0.001), and creatinine level (SDM = 0.312, 95% CI: 0.008 to 0.615, p = 0.044) than control patients. Subgroup analysis showed that allopurinol significantly decreased SBP whether or not antihypertensive drugs were being administered; a decrease in DBP was only seen in patients receiving antihypertensive drugs. Low-dose allopurinol (≤300 mg/day) was more effective at reducing SBP than high-dose (>300 mg/day) in patients receiving antihypertensive drugs. CONCLUSIONS: These results support that allopurinol decreases BP and creatinine levels in patients with hyperuricemia. KEY MESSAGES Allopurinol decreases SBP and DPB, and creatinine levels in patients with hyperuricemia. Allopurinol resulted in a significant decrease in SBP in patients with or without treatment of antihypertensive drugs. A dose of allopurinol of ≤300 mg per day might be more effective than a higher dose.

Downregulation of DOCK1 sensitizes bladder cancer cells to cisplatin through preventing epithelial-mesenchymal transition.

During the past several decades, resistance to single or multiple anticancer agents has posed a great challenge in cancer therapy. Dedicator of cytokinesis 1 (DOCK1), the first identified member in DOCK family, plays diverse roles in cellular processes, including tumorigenesis. In this study, we explored the biological role of DOCK1 in the chemotherapeutic resistance in bladder cancer and its underlying mechanism. Our results showed that the bladder cancer cell lines UM-UC-3 and J82 with higher DOCK1 are more resistant to cisplatin, whereas B87 cells with the lowest expression of DOCK1 exhibited the highest sensitivity to cisplatin. Down-regulation of DOCK1 with small interfering RNA (siRNA) increased the cisplatin sensitivity in bladder cancer cells. Moreover, treatment with cisplatin induced epithelial-mesenchymal transition (EMT), while transfection with Twist siRNA restored the chemosensitivity to cisplatin. In addition, we found that downregulation of DOCK1 reversed EMT program in bladder cancer cells. However, cotransfection with DOCK1 siRNA could not further enhance the cisplatin sensitivity and cellular phenotypic changes in tumor cells. Taken together, these results demonstrate that downregulation of DOCK1 could increase the chemosensitivity in bladder cancer cells via preventing cisplatin-induced EMT, suggesting that DOCK1 may serve as a potential therapeutic target in bladder cancer.

Basiliximab versus rabbit antithymocyte globulin as induction therapy for living-related renal transplantation: a single-center experience.

PURPOSE: To compare the long-term effects of the interleukin-2 receptor antagonist basiliximab versus rabbit antithymocyte globulin as an induction therapy for living-related renal transplantation. METHODS: This is a prospective, open-label, nonrandomized, controlled study including 213 cases of renal transplant. Immunosuppressive therapy containing calcineurin inhibitors, mycophenolate mofetil and steroids was applied in all cases. The interleukin-2 receptor antagonist group (IL2Ra group) included 108 cases with 20 mg basiliximab induction on Day 0 and Day 4. The other 105 cases comprised the rabbit antithymocyte globulin group (rATG group) with 1.0 mg/kg/day ATG induction from Day 0 to Day 4. The primary endpoint was biopsy-proven acute rejection. Other endpoints included delayed graft function (DGF), graft loss and death. RESULTS: All patients were followed up for 3 years. Acute rejection rates in the IL2Ra group and the ATG group were 5.6 and 3.8 % (P = 0.781), and the differences in the DGF rates, graft loss and death were insignificant between groups. All-cause infection rates in the IL2Ra and rATG groups were 26.9 and 43.8 % (P = 0.010). Urinary tract infections were more common in the rATG group than in the IL2Ra group (15.2 vs 6.5 %, P = 0.040). Specific viral infection rates were significantly different (18.1 % in rATG group vs 8.3 % in IL2Ra group, P = 0.035). CONCLUSIONS: IL2Ra and rATG had no significant differences as induction therapies during the perioperative period of living-related renal transplantation, according to acute rejection rates, DGF rates, graft loss, 1- and 3-year patient/graft survival rates. However, the incidence of infection, especially of urinary tract infection and specific viral infection, was higher in rATG-induced patients.

0.9% saline is neither normal nor physiological.

The purpose of this review is to objectively evaluate the biochemical and pathophysiological properties of 0.9% saline (henceforth: saline) and to discuss the impact of saline infusion, specifically on systemic acid-base balance and renal hemodynamics. Studies have shown that electrolyte balance, including effects of saline infusion on serum electrolytes, is often poorly understood among practicing physicians and inappropriate saline prescribing can cause increased morbidity and mortality. Large-volume (>2 L) saline infusion in healthy adults induces hyperchloremia which is associated with metabolic acidosis, hyperkalemia, and negative protein balance. Saline overload (80 ml/kg) in rodents can cause intestinal edema and contractile dysfunction associated with activation of sodium-proton exchanger (NHE) and decrease in myosin light chain phosphorylation. Saline infusion can also adversely affect renal hemodynamics. Microperfusion experiments and real-time imaging studies have demonstrated a reduction in renal perfusion and an expansion in kidney volume, compromising O2 delivery to the renal parenchyma following saline infusion. Clinically, saline infusion for patients post abdominal and cardiovascular surgery is associated with a greater number of adverse effects including more frequent blood product transfusion and bicarbonate therapy, reduced gastric blood flow, delayed recovery of gut function, impaired cardiac contractility in response to inotropes, prolonged hospital stay, and possibly increased mortality. In critically ill patients, saline infusion, compared to balanced fluid infusions, increases the occurrence of acute kidney injury. In summary, saline is a highly acidic fluid. With the exception of saline infusion for patients with hypochloremic metabolic alkalosis and volume depletion due to vomiting or upper gastrointestinal suction, indiscriminate use, especially for acutely ill patients, may cause unnecessary complications and should be avoided. More education regarding saline-related effects and adequate electrolyte management is needed.

The outcome of the proximal radial artery arteriovenous fistula.

BACKGROUND: Guidelines recommend placing native arteriovenous fistulas (AVFs) as far distally in the upper extremity as possible. If there are adequate veins and adequate arteries, a wrist fistula, which offers notably lower risks than grafts and catheters, would be the first choice for long-term hemodialysis. With increasing failure and difficulty to create wrist fistulas, we reviewed outcomes of the proximal radial AVF (PRAAVF) and demonstrate that it is an effective technique. METHODS: A systemic literature research was conducted in PubMed and related bibliographies. The focus of data extraction was primary failure, primary patency rates, and secondary patency rates after 1 and 2 years. Estimates were pooled with the random effects model, and meta-regression and sensitivity analysis were performed to explore heterogeneity. RESULTS: According to selection criteria formulated a priori, 10 articles (n = 1310) were included and finally analyzed after screening 1687 articles. The pooled primary failure was 12.3% (95% confidence interval [CI], 7.6%-17.0%; χ(2) = 70.8, I(2) = 87.3%), the primary patency, including primary failure, was 73.6% (95% CI, 52.4%-94.9%; χ(2) = 71.3, I(2) = 97.2%) at 1 year and 70.5% (95% CI, 50.6%-90.5%; χ(2) = 58.8, I(2) = 96.6%) at 2 years. Secondary patency was 80.0% (95% CI, 72.8%-87.2%; χ(2) = 24.42, I(2) = 75.4%) at 1 year and 73.7% (95% CI, 65.2%-82.2%; χ(2) = 28.51, I(2) = 79.0%) at 2 years. Individual variate meta-regression analysis found the definition of primary failure was a significant source of heterogeneity (P = .009). Steal syndromes developed in four of 832 (0.5%) of the PRAAVFs, and venous hypertension developed in four of 284 (1.4%). CONCLUSIONS: The PRAAVF presented low to moderate primary failure and high primary and secondary patency rates with acceptable complications. Consideration of the specific fistula is required when creating a vascular access, especially when a wrist fistula has failed or is predicted to be unsuccessful.

Protective effect of indomethacin in renal ischemia-reperfusion injury in mice.

OBJECTIVE: To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs (NSAIDs) in renal ischemia-reperfusion injury (IRI) and the cyclooxygenase (COX)-1/2 blockade association by indomethacin (IMT) in the mice model. METHODS: After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses: 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine (SCr) using enzyme-linked immunosorbent assay (ELISA) kits. Kidney samples were analyzed by hematoxylin and eosin (H&E) and immunohistochemistry stainings. RESULTS: The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage. The tumor necrosis factor α (TNF-α) activity in renal homogenates and interleukin 6 (IL-6) activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. CONCLUSIONS: There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.

Proteins induced by telomere dysfunction are associated with human IgA nephropathy.

Aging is one of the contributing risk factors for kidney diseases. Accumulating evidence prompts the view that telomere length in kidney tissue cells is an indicator for organismal aging. Previously identified aging markers (cathelin-related antimicrobial peptide (CRAMP), stathmin, elongation factor-1α (EF-1α), and chitinase) were associated not only with telomere driven aging in mice but also with human aging and chronic diseases. This study focuses on the relationship between these biomarkers and IgA nephropathy (IgAN) progression in the Chinese population. For 260 individuals, the four markers are determined in blind datasets using direct enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. The expression levels of CRAMP and chitinase increased in blood plasma, urine, and kidney tissues during human IgAN progression. And for the other nephropathy, such as systemic lupus erythematosus (SLE), diabetic nephropathy (DN), and focal segmental glomerulosclerosis (FSGS), there is no protein upregulation with telomere shortening. Moreover, a combination of CRAMP and chitinase can distinguish patients with IgAN from healthy individuals with 88.2%/92.5% (plasma) and 74.3%/84.2% (urine) sensitivity/specificity. These data provide the experimental evidence that telomere shortening and related inflammatory proteins are associated with human IgAN, and it could be a new direction for the disease progression study.

Extra-pulmonary tuberculosis infection in the dialysis patients with end stage renal diseases: case reports and literature review.

The diagnosis of extra-pulmonary tuberculosis (TB) seems relatively difficult due to the absence of specific symptoms and signs in patients on peritoneal dialysis or hemodialysis. We report four cases of extra-pulmonary tuberculosis on dialysis, with two cases on peritoneal dialysis and two cases on hemodialysis. The presentations, therapy, and outcomes of TB infection in these patients were reviewed. Otherwise, the English literature published in the PubMed database associating extra-pulmonary tuberculosis on dialysis over the last three decades is reviewed. A total of 61 studies containing 70 cases were included. The most common primary disease was diabetic nephropathy (22.86%, 16/70). The peritoneum (31.42%, 22/70), bone (21.42%, 15/70), and lymph node (20%, 14/70) were the most frequently infected. Single organ infection was common (90%, 63/70). Fever (58.57%, 41/70), pain (35.71%, 25/70), and enlarged lymph node (20%, 14/70) were the most common symptoms. Biopsy (67.14%, 47/70) and culture (40%, 28/70) provided most reliable methods for clear diagnosis of tuberculosis. The combined treatment of isoniazid, rifampicin, pyrazinamide, and ethambutol (44.29%, 31/70) was the most common therapy. The majority of patients improved (82.86%, 58/70); however, 12 cases got worse (17.14%), with 10 of them dying (14.29%). Physicians should be aware of the non-specific symptoms and location of infection, and consider tuberculosis in their differential diagnoses in dialysis patients presenting with symptoms such as fever, pain, and weight loss.

ß,ß-Dimethylacrylshikonin induces mitochondria dependent apoptosis through ERK pathway in human gastric cancer SGC-7901 cells.

ß,ß-Dimethylacrylshikonin, one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we discussed the molecular mechanisms of ß,ß-dimethylacrylshikonin in the apoptosis of SGC-7901 cells. ß,ß-Dimethylacrylshikonin reduced the cell viability of SGC-7901 cells in a dose- and time-dependent manner and induced cell apoptosis. ß,ß-Dimethylacrylshikonin treatment in SGC-7901 cells down-regulated the expression of XIAP, cIAP-2, and Bcl-2 and up-regulated the expression of Bak and Bax and caused the loss of mitochondrial membrane potential and release of cytochrome c. Additionally, ß,ß-dimethylacrylshikonin treatment led to activation of caspases-9, 8 and 3, and cleavage of poly (ADP-ribose) polymerase (PARP), which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. ß,ß-Dimethylacrylshikonin induced phosphorylation of extracellular signal-regulated kinase (ERK) in SGC-7901 cells. U0126, a specific MEK inhibitor, blocked the ERK activation by ß,ß-dimethylacrylshikonin and abrogated ß,ß-dimethylacrylshikonin -induced apoptosis. Our results demonstrated that ß,ß-dimethylacrylshikonin inhibited growth of gastric cancer SGC-7901 cells by inducing ERK signaling pathway, and provided a clue for preclinical and clinical evaluation of ß,ß-dimethylacrylshikonin for gastric cancer therapy.

The association between non-Hodgkin lymphoma and methylation of p73.

To investigate the effects of methylation of the p73 gene on the pathogenesis of non-Hodgkin lymphoma (NHL), the methylation status of the p73 gene promoter and the expression of p73 mRNA were examined in NHLs by methylation-specific polymerase chain reaction (MSP) and reverse transcription-polymerase chain reaction, respectively; p73 protein was detected by Western blotting analysis. Furthermore, the expression of p73 mRNA in NHL cells treated with 5-Aza-2'-deoxycytidine was analyzed. MSP results revealed that the promoter of p73 was methylated in 87.5% of NHLs but was not methylated in reactive hyperplasia lymph node samples. The expression of p73 mRNA was not detected in 83.33% of NHLs but was detected in all of the reactive hyperplasia lymph node samples. The p73 protein was not detected in 91.67% of NHLs but was detected in all of the reactive hyperplasia lymph node samples. The expression of p73 mRNA was detected in NHL cells treated with 5-Aza-2'-deoxycytidine. The inactivation of p73, predominantly by methylation, may be involved in the pathogenesis of NHLs.

Ginsenoside Rg3 inhibits CXCR4 expression and related migrations in a breast cancer cell line.

BACKGROUND: Ginsenoside Rg3 is an extract from the natural product ginseng. Previous studies have linked Rg3 with anti-metastasis of cancer in vivo and in vitro. CXC receptor 4 (CXCR4) is a vital molecule in migration and homing of cancer to the docking regions. METHODS: In this study, the effects of Rg3 on CXCR4 expression were investigated in a breast cancer cell line. Immunohistochemistry, chemotaxis and wound healing mobility assays were performed in cultured MDA-MB-231 cells. RESULTS: At a dosage without obvious cytotoxicity, Rg3 treatment elicits a weak CXCR4 stain color, decreases the number of migrated cells in CXCL12-elicited chemotaxis and reduces the width of the scar in wound healing. CONCLUSION: This work suggests that Rg3 is a new CXCR4 inhibitor from a natural product.

Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury.

Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP.

[Clinical study of single-dose of recombinant humanized anti-CD3 monoclonal antibody injection in kidney transplant recipients].

OBJECTIVE: To evaluate short-term and long-term safety of using single-dose escalation of recombinant humanized anti-CD3 monoclonal antibody (OKT3) in kidney transplantation recipients. METHODS: A total of 29 recipients of cadaveric kidney transplant from June 2008 to December 2008 were sequently assigned to receive single-dose intravenous injection of OKT3 with different doses of 2.5 mg (n = 9), 5.0 mg (n = 10) and 10.0 mg (n = 10) at Days 7 - 14 post-operation. Meanwhile, a control group was established by selecting kidney transplant recipients, who did not participate in the trial in the same period. All patients were followed up for at least 2 years. During this period, liver function, kidney function, hemoglobin and other biochemical indicators were monitored and adverse events recorded over time. RESULTS: No obvious first dose effect was observed, except low heat (7/29), chills (4/29), mild liver damage (2/29), upper respiratory tract infection and headache (1/29) across all doses. Other adverse reactions were mild, unrelated with doses. The 2-year patients/grafts survival rates of treatment group and control group were 100%/100%, and 100%/97%, respectively. The incidence of acute rejection confirmed by renal biopsy was 6.9% (2/29) and 10.0% (3/30) in treatment group and control group, respectively. The incidence of lung infection was 10.3% (3/29) and 13.3% (4/30), respectively. The values of serum creatinine at 1 week and 3, 6, 12, 24 months showed no statistically significance in two groups (all P > 0.05). CONCLUSION: It is safe to use single-shot OKT3 intravenously in kidney transplant recipients. The recombinant humanized OKT3 may be an effective immunosuppressive agent with milder toxicity for solid organ transplantation.

Feasibility of diagnosing renal allograft dysfunction by oligonucleotide array: Gene expression profile correlates with histopathology.

BACKGROUND: Effective non-invasive monitoring method to tell histopathology is a big challenge in renal transplantation. METHODS: We used 70-mer long oligonucleotide array with 449 immune related genes to determine gene expression profiles of peripheral blood mononuclear cells (PBMCs) under different immune status including stable renal function (TX), acute tubular necrosis (ATN), biopsy conformed acute rejection (AR), clinical rejection with pathology of borderline changes (BL), clinical rejection without biopsy proven/presumed rejection (PR) and renal dysfunction without rejection (NR). RESULTS: Distinct molecular expression signatures in each group were found to correlate with histopathology. And we concluded that B cell chemokine CXCL13 and mast cell may play a role in renal allograft rejection through significant difference analysis and functional pathway analysis. CONCLUSIONS: It provides a potential non-invasive method for monitoring renal allograft function and immune status of renal transplant recipients.

[The effects of two health education models on psychological and nutritional profile of patients waiting for kidney transplantation].

OBJECTIVE: To investigate the effects of two health education models on the psychology and nutrition of patients waiting for cadaveric renal transplantation. METHODS: A total of 125 patients waiting for cadaveric renal transplantations were involved in our study. They were diagnosed with chronic renal failure in our hospital during September 1, 2009 to August 30, 2010. The patients were randomly divided into control group (n = 62) and observational group (n = 63). Patients in the control group received traditional health education with routine preoperative education during hospitalization. In the observational group, full-time nurses assessed the nutrition status of each patient and monitored the data. The observational patients were followed up and were given dietary guidance and knowledge of transplantation. Various kinds of education formats were adopted in observational group to provide communication opportunities between patients and surgeons in charge as well as patients who underwent transplantation. Psychological testings of patients in both groups were tested by self-rating anxiety scale (SAS) and self-rating depression scale (SDS) before and after the health education. Triceps skinfold thickness (TSF), mid-arm muscle circumference (MAMC) and biochemistry index were also tested. Psychological and nutritional status of patients in the two groups was compared. RESULTS: There were no significant differences in scores of the SAS, SDS, TSF, Hb, and albumin (Alb) between the two groups (all P > 0.05) before health education. After health education, SAS and SDS in observational group were lower than those in the control group (40.02 ± 9.05 vs 47.05 ± 10.32, 42.70 ± 10.01 vs 50.83 ± 10.12; both P < 0.01). Both TSF and Hb were elevated after education (P < 0.001 or 0.05). Alb was significantly elevated in the observational group [(35.67 ± 6.19) g/L vs (37.48 ± 5.09) g/L, P < 0.01]. CONCLUSION: Comprehensive and various health education methods can significantly alleviate mental stress and improve nutrition of the patients waiting for kidney transplantation, which is helpful for patients facing disease positively and having a better quality of life.