12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74645/1/j.1432-2277.2006.00414.x.pd

Everolimus with Optimized Cyclosporine Dosing in Renal Transplant Recipients: 6-Month Safety and Efficacy Results of Two Randomized Studies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74668/1/j.1600-6143.2004.00389.x.pd

A randomized controlled trial of Cyclosporine withdrawal in renal-transplant recipients: 15-year results

Background. In renal transplantation, the immunosuppressive efficacy of cyclosporine is counterbalanced by its nephrotoxicity. Although cyclosporine improves short-term graft survival, its long-term effects are unclear. Methods. Recipients of first cadaver renal transplants were randomized into three groups between 1983 and 1986: azathioprine and prednisolone alone (AP, n= 158), long term cyclosporine alone (Cy, n= 166), and short-term cyclosporine followed by azathioprine and prednisolone (CyAP, n = 165). All groups received methylprednisolone induction. Results. There were no significant differences in patient survival at 15 years (48 vs. 56 vs. 51%, P=0.14), and 15-year graft survival (censored for death) in those patients in the CyAP group (47 vs. 44 vs. 59%, P=0.06) was not significantly different statistically. When deaths or graft losses before 12 months were censored, the differences in 15-year graft survival between the groups were significant (58%, 51%, 70%, P=0.01). The CyAP group also had lower mean serum creatinine at all time points beyond 3 months posttransplant out to 10 years (143 vs. 169 vs. 131 μmoles/L, P=0.04). Per protocol analysis, after censoring patients at change in therapy, increased the observed differences in 15-year graft survival between the groups (54 vs. 38 vs. 65%, P=0.01). Conclusion. Survival and function of first cadaveric kidney transplants is improved by use of short-term cyclosporine followed by azathioprine and prednisolone. Long-term cyclosporine use reduces long-term graft survival

Administration of erythropoiesis-stimulating agents in patients undergoing haemodialysis: A time and motion study

International guidelines recommend treatment of anaemia due to chronic kidney disease (CKD) with erythropoiesis-stimulating agents (ESAs).To document the time required and the cost in terms of nursing time to prepare and administer ESAs to patients on facility based haemodialysis (HD) with anaemia due to CKD before and after the introduction of long-acting ESAs.A time and motion study was implemented at four HD units in Australia to determine the time and costs associated with preparing and administering ESAs before and after the introduction of long-acting ESAs.This was a prospective, observational study of workplace practices at four HD units in Australia.Outcome data included the time taken to prepare, and administer ESAs.The time costs of preparation and administration per patient per year had a wide variability within each unit and ranged from Australian AUD$55.75 (38 euros) to AUD$90.49 (62 euros) before the introduction of long-acting ESAs. This dropped by 73-80% following the introduction of long-acting ESAs, representing an annual cost savings of between AUD$2,591 and AUD$5,914 if all patients on HD were switched to a long acting ESA.Switching from a short-acting to a long-acting ESA in HD units leads to a significant reduction in time costs of health professionals in preparation and administration of ESAs by up to 80%. Practical application: This time and motion study has added further evidence on reduction of human effort by taking advantages of new research development, such as the long acting ESAs

Time course of upregulation of fibrogenic growth factors in a rodent model of chronic renal allograft rejection

Upregulation of growth factors has been shown in CR but the time point at which this occurs in not known. The aim of this study was to examine the time course of upregulation of growth factors and correlate this with the macrophage and myofibroblast interstitial infiltrate. Methods: Using a rat model of CR (F344 kidney donor to Lewis recipient), infiltration by ED1+ macrophages and proliferation of α-smooth muscle actin (α-SMA) and desmin-expressing cells was examined using immunohistochemistry. In addition, expression of mRNA for interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), basic-fibroblast growth factor (b-FGF) and vascular endothelial growth factor (VEGF) was studied using a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique. Native Lewis rat kidney and Lewis–Lewis isografts were used as controls. Results: Immunohistochemical staining of ED1+ cells showed a marked increase in the macrophage infiltrate of allografts compared to isografts at all time periods (P=0.0002) peaking at weeks 8–12 after transplantation. Expression of α-SMA was also increased in allografts (P=0.002). RT-PCR analysis showed that mRNA for TGF-β was maximally upregulated in allografts in comparison to isografts at week 8 after engraftment (P=0.05) and declined thereafter, although remained at elevated levels compared to controls. IFN-γ and b-FGF gene expression was increased in allografts late in the post-transplantation period. Conclusion: Early infiltration of macrophages and production of TGF-β1 was followed by later upregulation of fibrogenic growth factors and myofibroblasts associated with interstitial fibrosis and organ dysfunction