Fc-dependent depletion of activated T cells occurs through CD40L-specific antibody rather than costimulation blockade.

Although the underlying mechanisms are not well understood, it is generally believed that antigen recognition by T cells in the absence of costimulation may alter the immune response, leading to anergy or tolerance. Further support for this concept comes from animal models of autoimmunity and transplantation, where treatments based on costimulation blockade, in particular CD40 ligand (CD40L)-specific antibodies, have been highly effective. We investigated the mechanisms of action of an antibody to CD40L and provide evidence that its effects are dependent on the constant (Fc) region. Prolongation of graft survival is dependent on both complement- and Fc receptor-mediated mechanisms in a major histocompatibility complex (MHC)-mismatched skin transplant model. These data suggest that antibodies to CD40L act through selective depletion of activated T cells, rather than exerting immune modulation by costimulation blockade as currently postulated. This finding opens new avenues for treatment of immune disorders based on selective targeting of activated T cells.

Prevalence and management of anaemia in renal transplant recipients: data from ten European centres.

BACKGROUND: Although it is a known predictor of mortality, there is a relative lack of recent information about anaemia in kidney transplant recipients. Thus, we now report data about the prevalence and management of post-transplant anaemia (PTA) in Europe 5 years after the TRansplant European Survey on Anemia Management (TRESAM) study. METHODS: In a cross-sectional study enrolling the largest number of patients to date, data were obtained from 5,834 patients followed at 10 outpatient transplant clinics in four European countries using the American Society of Transplantation anaemia guideline. RESULTS: More than one third (42%) of the patients were anaemic. The haemoglobin (Hb) concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (r = 0.4, p < 0.001). In multivariate analysis, eGFR, serum ferritin, age, gender, time since transplantation and centres were independently and significantly associated with Hb. Only 24% of the patients who had a Hb concentration <110 g/l were treated with an erythropoiesis-stimulating agent. The prevalence of anaemia and also the use of erythropoiesis-stimulating agents were significantly different across the different centres, suggesting substantial practice variations. CONCLUSIONS: PTA is still common and under-treated. The prevalence and management of PTA have not changed substantially since the TRESAM survey.

Biopsy-proven acute interstitial nephritis associated with the tyrosine kinase inhibitor sunitinib: a class effect?

Since their introduction in 2006, the tyrosine kinase inhibitors (TKI) Sunitinib and Sorafenib have become the standard of care for many patients with renal cancer. They are generally well tolerated and have not been significantly implicated in renal toxicity. We report the first biopsy confirmed occurrence of acute interstitial nephritis in a patient receiving treatment with Sunitinib for metastatic renal cell cancer. However, two previous descriptions of interstitial nephritis related to treatment with TKIs, combined with this current report suggest that TKI therapy could be associated with this rare but life-threatening complication.

Does the surgeon's experience impact on radiocephalic fistula patency rates?

Establishing successful long-term hemodialysis access remains a major challenge. The primary aims of this study were to determine whether primary success and primary and secondary patency rates of a series of consecutive radio-cephalic fistulae (RCF) were affected by the experience of the surgeon. The secondary aims were to assess complications, and to compare results with patency rates from the literature. All native fistulae (AVF) created in our unit between January 1, 2002 and December 31, 2005 were analyzed retrospectively. The RCF were identified and divided into group A (RCF fashioned by the consultant surgeon), and group B (fashioned by the junior surgeons within the unit). Demographic characteristics, risk factors, primary success rate (patent fistula at discharge), and primary and secondary patency rates were compared between each group using chi-squared test. During this period, 552 AVF were created. Of the 195 RCF, there were 153 fistulae in group A and 42 in group B. Median follow-up was 22 months for both groups. There was no difference with regards to age, sex ratio, prevalence of diabetes, and cardiovascular disease. The primary success rate in group A and B was 94.2% and 81%, respectively (p < 0.01). Primary and secondary patency rates at 22 months were 80%, 93%* and 74%, 81%* in group A and B, respectively (*p < 0.025). Even within group B, these results compare very favorably with the published literature. These results suggest that the placement of a RCF should be performed by the most experienced member of a team dedicated to vascular access creation or at least under his supervision.

Dialysis or not? A comparative survival study of patients over 75 years with chronic kidney disease stage 5.

BACKGROUND: The number of elderly patients with chronic kidney disease (CKD) stage 5 is steadily increasing. Evidence is needed to inform decision-making for or against dialysis, especially in those patients with multiple comorbid conditions for whom dialysis may not increase survival. We therefore compared survival of elderly patients with CKD stage 5, managed either with dialysis or conservatively (without dialysis), after the management decision had been made, and explored which of several key variables were independently associated with survival. METHODS: A retrospective analysis of the survival of all over 75 years with CKD stage 5 attending dedicated multidisciplinary pre-dialysis care clinics (n=129) was performed. Demographic and comorbidity data were collected on all patients. Survival was defined as the time from estimated GFR<15 ml/min to either death or study endpoint. RESULTS: One- and two-year survival rates were 84% and 76% in the dialysis group (n=52) and 68% and 47% in the conservative group (n=77), respectively, with significantly different cumulative survival (log rank 13.6, P<0.001). However, this survival advantage was lost in those patients with high comorbidity scores, especially when the comorbidity included ischaemic heart disease. CONCLUSIONS: In CKD stage 5 patients over 75 years, who receive specialist nephrological care early, and who follow a planned management pathway, the survival advantage of dialysis is substantially reduced by comorbidity and ischaemic heart disease in particular. Comorbidity should be a major consideration when advising elderly patients for or against dialysis.