Volume 6 Issue 10, October 2010

The results of a large observational study seem to confirm an association between early initiation of dialysis and increased mortality that is not fully explained by the presence of comorbidities and other confounding variables. However, this paradoxical association may be an artifact resulting from the inaccuracy of using plasma creatinine levels to estimate glomerular filtration rates in patients with severely impaired renal function.

Many clinical guidelines recommend thiazide diuretics as first-line treatment for hypertension, even in individuals with mild chronic kidney disease (CKD). However, results from the ACCOMPLISH trial add to growing evidence that thiazide-based therapy does not retard progression of CKD. Re-evaluation of the role of these agents in the management of hypertension in patients with CKD might be appropriate.

Almost 25 years after recombinant human erythropoietin first became available to treat anemia in patients with chronic kidney disease, the optimal use of erythropoiesis-stimulating agents (ESAs) is as unclear as ever. One reason for this uncertainty is that the risks associated with correction of anemia using ESAs could be either related to patients' hemoglobin levels or to off-target effects of these agents.

The immune system has evolved to ensure protection against ever changing microbial pathogens. The potential of lymphocytes to recognize 'self' is controlled by a process called 'self tolerance'. Improved understanding of the mechanisms of immunological tolerance is key to understanding the pathogenesis of autoimmune disorders and cancers, and may lead to strategies to harness tolerance to replace the lifelong need for immunosuppressive drugs after organ transplantation. In this Review, Waldmann provides an overview of the mechanisms of self tolerance and assesses the prospects of translating this knowledge to patient care.

Promoting the development and maintenance of regulatory responses through the promotion of regulatory T (T_REG) cells represents a promising approach for the induction of transplantation tolerance. In this Review, Li and Turka provide an overview of T_REG cells, focusing on the challenges, opportunities, and emerging approaches in exploiting FOXP3⁺ T_REGcells for the induction of transplant tolerance.

B cells have important roles in both graft rejection and in transplantation tolerance. In this Review, Kirk and colleagues discuss the mechanisms involved in the induction of B-cell tolerance and describe current and emerging therapies for treating antibody-mediated graft rejection.

The success of organ transplantation is limited by the host immune response to the foreign graft and the adverse effects of chronic immunosuppressive therapy. The induction of mixed chimerism through the transplantation of donor hematopoietic stem cells is an effective approach towards achieving tolerance to donor tissue and holds great promise in improving transplant survival. This Review describes recent insights into the induction of transplantation tolerance through mixed chimerism and discusses the potential and challenges of this approach.

A critical gap in the field of transplantation tolerance is the lack of available tests or biomarkers to indicate when a patient has become partially or totally tolerant to their graft. Here, Hernandez-Fuentes and Lechler discuss advances in the development of biomarkers of transplantation tolerance and describe the potential utility of such biomarkers for the modification of protocols in clinical practice.

The past few decades have seen great advances in genetics and molecular cell biology. Advances in chemistry and engineering have enabled increased data throughput, permitting the study of complete sets of molecules with increasing speed and accuracy using techniques such as genomics, transcriptomics, proteomics, and metabolomics. In this Review, the authors discuss the opportunities that molecular diagnostic tools have to offer both basic scientists and translational researchers in the field of transplantation.

Allograft rejection is a major barrier to transplantation. To prevent allograft rejection, transplant recipients require long-term immunosuppression, which is associated with increased susceptibility to infection, increased risk of malignancy, and increased morbidity and mortality. A major goal in transplantation, therefore, is the induction of tolerance, to enable indefinite allograft survival without the need for life-long immunosuppression. This focus issue on tolerance in transplantation contains six Reviews written by experts in the field of tolerance, describing tolerance mechanisms, how these mechanisms can be studied to assess prognosis, and how they can be harnessed to induce tolerance.