Liang Ren

The effects of early rapid corticosteroid reduction on cell-mediated immunity in kidney transplant recipients

While being helpful in the prevention and treatment of acute rejection (AR) in kidney transplant patients, corticosteroids have many side effects associated with their long-term use. It is reasonable to minimize these adverse effects without affecting their benefits. In this prospective trial, we investigated the effects of early rapid corticosteroid reduction on the cell-mediated immunity, measured by the Cylex® Immune Cell Function Assay, the incidence of AR and infection and the allograft function after kidney transplantation to assess the feasibility of this strategy in the Chinese population. A method of rapid reduction of corticosteroid to 10 mg/day seven days post-transplantation was adopted for the experimental group, and the standard corticosteroid therapy for the control group. Comparison of intracellular ATP values detected two weeks post-transplantation for the control group (324±45 ng/mL) and the experimental group (345±91 ng/mL) did not reveal a significant difference (p>0.05). The incidence of AR was analogous between groups (p>0.05), while an increased incidence of infection was observed in the control group (53%) versus the experimental group (22%), where p<0.05. The mean ATP concentration was lower in the control group (235±35 ng/mL) than that of the experimental group (286±16 ng/mL) when infection occurred (p<0.05). The mean allograft function was similar between groups (p>0.05). Rapid corticosteroid reduction early after kidney transplantation does not cause a significant rise in patient immunity or increase the incidence of AR, and contributes to infection control. This strategy may serve as a safe and effective therapy for kidney transplant patients in the Chinese population.

Signal Transducer and Activator of Transcription 1 and Matrix Metalloproteinase 3 Genetic Expression and Clinical Significance on Urothelial Tumors After Renal Transplantation

OBJECTIVE The objective of this study was investigate signal transducer and activator of transcription 1 and matrix metalloproteinase 3 genetic expression and clinical significance on urothelial carcinoma after renal transplantation. METHODS This study included 51 patients with histopathologically proven urothelial carcinoma, 16 of whom had undergone renal transplantation, and 35 others who had not and served as a control group. Human genome oligo-arrays were used to analyze the gene expression spectrum of the tumors. STAT1 and MMP3 expression in urothelial carcinoma was determined using real-time-polymerase chain reaction (RT-PCR) and immunohistochemistry staining. No prisoners or organs from prisoners were used in this study. RESULTS Among the transplantation group, 35 genes were up-regulated. The functions of 23 genes were known or partly known. Additionally, 76 genes were down-regulated in the transplantation group. The function of 46 genes was known or partly known. Pathway analysis of differences in gene expression between the groups revealed 23 groups of pathways that exhibited statistical significance (P < .05). The differences in the levels of expression of STAT1 and MMP3 were significant (P < .05). CONCLUSIONS Differences in gene expression profiles of STAT1 and MMP3 exist between patients who have and those who have not undergone renal transplantation. STAT1 and MMP3 may be potential targets for the chemoprevention of posttransplantation urothelial carcinoma.

Prograf produces more benefits for CYP3A5 low expression patients in early stage after kidney transplantation

OBJECTIVE This study is to analyze concentration changes of the prolonged-release and shorter-acting formulation of tacrolimus in patients with different CYP3A5 genotypes after kidney transplantation. METHODS A single-factor retrospective analysis was performed in patients underwent allogeneic kidney transplantation with postoperative administration of Advagraf or Prograf in our hospital from May 2013 to June 2014. The CYP3A5 genotypes were determined, and tacrolimus trough concentrations in whole blood were measured within 28days after transplantation. The rates of acute rejection rate, chronic rejection and infection were recorded and compared after one year follow-up after surgery. RESULTS The study included 106 patients administered Advagraf (45 cases) or Prograf (61 cases). The low expression genotype of CYP3A5 was detected in 40 (37.7%) patients. A higher dose of Advagraf was required to increase the tacrolimus trough concentrations within 21days after transplantation. Moreover, a higher dose for Advagraf than Prograf was required to increase the tacrolimus trough concentrations in low expression patients. In the low expression patients, Prograf more frequently achieved the target tacrolimus trough concentrations within seven days after transplantation (five days: 7.14% vs. 84%, P=0.001; seven days: 33.33% vs. 77.78%, P=0.001). The patient and kidney graft survival rates one year after transplantation both were 100%. The estimated glomerular filtration rate showed no significant difference between different CYP3A5 phenotypes or formulations of tacrolimus (P>0.05). However, the incidence of infections was higher in the Advagraf group in low expression patients (P<0.05). CONCLUSION Tacrolimus of different formulations had different impact on patients with different CYP3A5 genotypes after kidney transplantation.

Improvement in Severe Mycophenolic Acid-associated Gastrointestinal Symptoms after Changing Enteric-coated Mycophenolate Sodium to Mizoribine in Renal Transplant Recipients: Two Case Reports

Clinical results point to a better gastrointestinal tolerability with enteric-coated mycophenolate sodium as compared to mycophenolate mofetil. However, some transplant recipients who are treated with enteric-coated mycophenolate sodium still experience gastrointestinal symptoms. We herein present two cases of renal transplant recipients with severe gastrointestinal symptoms who were switched from enteric-coated mycophenolate sodium to mizoribine, and the symptom reversal effects were evaluated using the Gastrointestinal Symptom Rating Scale. The results of this study showed a significant improvement in severe gastrointestinal symptoms in renal transplant recipients after converting from enteric-coated mycophenolate sodium to mizoribine.

Successful Renal Transplantation in a Patient with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab in China.

IntroductIon Hemolytic uremic syndrome (HUS) is a rare disease characterized by thrombocytopenia and acute renal failure. Atypical HUS (aHUS) accounts for approximately 10% of all HUS cases. The pathogenesis of aHUS is mainly associated with gene mutations in complement factor H, complement factor I, and membrane cofactor protein (MCP). The prognosis of aHUS is generally poor. Totally, 60% of patients develop renal failure or even die within 1 year. The efficacy of blood transfusion, dialysis, or plasmapheresis is not excellent. Kidney transplantation is an important method for treating end‐stage renal diseases. Studies from other countries show that for patients with complement system function disorders caused by aHUS, the transplantation success rate is low and the postoperative aHUS recurrence rate is high.[1‐3] With the introduction of the complement component 5 (C5) monoclonal antibody eculizumab (Alexion, CT, USA), the long‐term survival of patients significantly improves.[1]

Gene Profiling of Cyclosporin-Enhanced Transitional Cell Carcinoma in Rat Model

OBJECTIVE We sought to study the effect of cyclosporine (CsA) on development of malignancy. MATERIALS AND METHODS The observation was performed in a rat model, in which transitional cell carcinoma of urinary bladder was induced with N-butyl-N-(-4-hydroxybutyl) nitrosamine. CsA was added in the food for the rats. At the end of 30 weeks, we examined the tumor burden in the urinary bladders, and compared gene expressions between the CsA-enhanced and non-CsA-enhanced tumor groups by gene profiling. RESULTS CsA feeding increased tumor burden: 2.3 +/- 0.9 versus 1.1 +/- 0.5 g (P < .05). Gene profiling showed many variations involved in CsA enhanced malignant development. Twenty-three genes with known functions were upregulated, and 46 genes with known functions downregulated. In all, 111 genes were involved in the CsA-enhanced malignant development. The regulated genes in the present study constituted 23 pathways mostly involved in carcinogenesis. CONCLUSIONS CsA plays an important role in tumor development through gene regulation, which may constitute pathways to malignant progression.