Aim. Serum cystatin C (SCysC) has been proposed as a better marker of glomerular filtration rate (GFR) than serum creatinine (Scr). However, few data are available in renal transplant patients, especially, during the early postoperative phase. Methods. Thirty-nine renal transplant patients (22 men/17 women) were recruited for determination of SCysC and Scr before operation, at 1 week and at 4 weeks after operation. SCysC was determined by particle-enhanced turbidimetric immunoassay. Creatinine clearance (Ccr) was calculated using the Cockcroft-Gault formula. Results. SCysC and Scr levels significantly decreased with the recovery of allograft function. SCysC showed a significant correlation with Scr and Ccr. The relationship between SCysC and Scr showed a positive correlation (r=.849 preoperation, and r=.940 postoperation). The relationship between SCysC and Ccr revealed a negative correlation (r=.857 preoperation, and r=.876 postoperation). At the Ccr level of 50 to 80mL/min/1.73m2, the correlation between SCysC and Ccr (r=.778) was significantly better than that between Scr and Ccr (r=.553; P=.032). The concentration of SCysC was not affected by age, gender, height, body weight, hemoglobin, serum protein, glucose, or mycophenolate mofetil or azathioprine dosage. However, corticosteroids slightly increased the level of SCysC and cyclosporine (CsA) decreased it. The area under the curve of the receiver operating characteristic curve for SCysC and Scr are 0.964 and 0.915, respectively (P<.05). Conclusion. Although the concentration may be slightly influenced by prednisolone and CsA, SCysC is more sensitive than Scr to detect early and moderate deterioration of GFR in adult renal transplant recipients.

Introduction. We sought to investigate whether there was a difference between cyclosporine (CsA) and mycophenolate mofetil (MMF) to affect the expression of Fractalkine/ CX3CR1 in chronic allograft nephropathy (CAN). Methods. The Sprague-Dawley Wistar rat accelerated kidney sclerosis model was performed as modified from the procedure of Kamada. Recipients were divided into three oral treatment groups (each group n=8): group A was CsA 10mg/kg•d for 10 days followed by vehicle; group B was CsA 10mg/kg•d for 10 days followed by CsA 6mg/kg•d; group C was CsA 10mg/kg•d for 10 days followed by MMF 20mg/kg•d. Pathological changes graded according to Banff 97 Standards were observed at 4, 8, and 12 weeks posttransplantation. The immunohistochemistry and quantitative real-time fluorescence polymerase chain reaction (PCR) were used to assess the distribution and expression of Fractalkine/CX3CR1 in the grafted kidney. Results. Fractalkine/CX3CR1 were mostly expressed in the tubulointerstitium and tubular epithelial cell basolateral membrane. A proportion of the vessel showed positive staining for Fractalkine/CX3CR1, occasionally in glomerular parietal wall cells. The expression of Fractalkine/CX3CR1 in grafted kidneys at all the time points was significantly less in the MMF than in the CsA group or the control group (P<.05). Real-time fluorescence quantitative PCR revealed similar outcomes as immunohistochemistry. The expression of Fractalkine coincided with CX3CR1. Conclusion. Fractalkine/CX3CR1 may play an important role in the development of interstitial fibrosis in CAN. Different immunosuppresants have various effects on expression of the Fractalkine/CX3CR1.

Aim. Fractalkine/CX3CR1 system may contribute to the pathogenesis of renal allograft chronic rejection (CR). Vascular endothelial growth factor (VEGF) is an endothelial mitogen, which shows increased expression in inflammation and vasculopathy. This study sought describe the expression and distribution of Fractalkine/CX3CR1 and VEGF, and their relationship to human renal allograft CR. Methods. Renal tissue from 10 patients with CR was examined for Fractalkine/CX3CR1 and VEGF protein by immunohistochemistry for comparison with patients displaying hyperacute rejection (n=10), acute rejection (n=10), and normal kidneys (n=10). All patients were selected based upon histologically proven diagnoses between 1992 and 2003. Results. Immunohistochemistry revealed that Fractalkine/CX3CR1 were mostly expressed in the tubulointerstitium and tubular epithelial cell basolateral membrane. Some vessels showed positive staining for Fractalkine/CX3CR1 as well as occasionally glomerular parietal wall cells. Among the CR group, VEGF was mostly expressed in tubular epithelium and the tubulointerstitium. A proportion of glomeruli and vessels had positive staining for VEGF, which was up-regulated most strikingly in the interstitial compartment in CR. There was markedly increased expression of Fractalkine/CX3CR1 and VEGF protein in the interstitium of the CR compared with other groups (P<.05). VEGF colocalized with the expression of Fractalkine/CX3CR1. Conclusion. Fractalkine/CX3CR1 and VEGF may play an important role in the development of interstitial fibrosis via mononuclear cell-induced cytokine production and myofibroblast stimulation in CR. Further studies are necessary to identify the role in the pathogenesis of CR.

Purposes. To compare the pharmacokinetic parameters of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) after single and multiple oral administration of mycophenolate mofetil (MMF) in Chinese renal transplant patients with those of recipients in other countries. Methods. Twelve Chinese renal transplant patients after an overnight fast received a single 1g dose of MMF before renal transplantation. Thereafter the patients received 1g MMF twice a day up to and on the day 12 after renal transplantation. The concentrations of MPA and MPAG were simultaneously measured by RP-HPLC. The concentration-time data were examined with Drug and Statistics pharmacokinetic software. Using paired samples t test (self-contrast) with SPSS statistical software (a=0.05), we compared the pharmacokinetic parameters between single and multiple doses. Results and discussions. The MPA concentration-time profiles were fitted to a twocompartment open model; MPAG concentration-time profiles were fitted to a singlecompartment open model. Compared with the literature reports, the main pharmacokinetic parameters of MPA and MPAG shown by our research revealed some differences. The parent drug MMF was undetectable in plasma during oral administration. A secondary peak of MPA occurred at 6 to 10 hours, which was attributed to enterohepatic recirculation. There was significant variation in MPA and MPAG plasma concentrationtime data among subjects. It is suggested that therapeutic drug monitoring should be applied for dosage optimization.

Aims. It is increasingly recognized that expression of cytoprotective genes in grafts can affect the progress of chronic allograft nephropathy (CAN). Little is known about the influence of different immunosuppressive regimens on expression of cytoprotective genes in allografts undergoing CAN. We investigate whether there is difference between rapamycin (Rapa) and FK506 in the expression of cytoprotective genes in rat kidney allografts undergoing CAN. Methods. Sprague-Dawley rat renal grafts were orthotopically transplanted into Wistar rats following the procedure of Kamada with our modification. The recipients were divided into three oral treatment groups: group 1: vehicle group (cyclosporine [CsA] 10mg/kg•d×10 days followed by vehicle); group 2: Rapa group (CsA 10mg/kg•d×10d followed by Rapa 0.8mg/kg•d); group 3: FK506 group (CsA 10mg/kg•d×10d followed by FK506 0.15mg/kg • d). At the same times after transplantation, the rats were sacrificed to harvest the renal allografts. The expression of four cytoprotective genes, A20, heme oxygenase (HO)-1, Bcl-2, and Bcl-X/L were analyzed in these grafted kidneys by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Results. Four cytoprotective genes were all detected in rat kidney allografts undergoing CAN. The expression of A20 in the Rapa group was significantly higher than that in the FK506 or the vehicle group (P<.05). There was no significant difference between the Rapa group and FK506 group in the expressions of HO-1, Bcl-2, and Bcl-X/L. Conclusions. We demonstrate that various immunosuppressive agents have different effects on the expression of cytoprotective genes.