Articles in 2010

Renal fibrosis is the common end point of virtually all progressive kidney diseases and a detailed understanding of the underlying mechanisms is required for the development of effective therapeutic strategies. In this Review, Boor and colleagues discuss the most recent advances in renal, or more specifically, tubulointerstitial fibrosis. Consideration is given to novel mechanisms as well as potential treatment targets based on different cell types.

Low pre-dialysis blood pressure is associated with an increased risk of mortality, but whether a high blood pressure level affects outcomes among patients on dialysis—as it does in the general population—is unclear. A recent study has found that higher systolic blood pressure measurements obtained outside the dialysis unit are associated with an increased risk of death, but that standard blood pressure recording in the dialysis unit has limited usefulness as a prognostic indicator.

A recent randomized clinical trial concluded that implantation of a stent graft plus angioplasty was superior to angioplasty alone for the treatment of stenosis at the venous anastomosis of an arteriovenous graft. However, concerns regarding the reliability of the results of this trial suggest that additional investigations are necessary.

A new pathologic classification scheme for diabetic nephropathy, in which only glomerular lesions are used to classify renal damage associated with either type 1 or type 2 diabetes, has been developed in association with the Renal Pathology Society. Given the heterogeneity of the renal lesions underlying diabetic nephropathy and the complex natural history of the disease, this scheme is not yet ready for clinical application but should be considered an important first step towards the development of a clinically useful classification system.

The management of patients with hemolytic uremic syndrome is challenging, and strategies for accurate diagnosis and effective treatment are needed. Intensive research over the past several years has revealed dysregulation of the complement system to be the main underlying cause of the syndrome, making this system the target of promising novel diagnostic and treatment strategies.

Many immunosuppressive agents used in renal transplantation are associated with an increased risk of cancer, and malignancy is the third most common cause of death among renal transplant recipients at all time points after transplantation. In this Review, Rama and Grinyó describe the epidemiological and clinical characteristics of common tumor types that occur in renal transplant recipients. They also discuss the potential pathogenic mechanisms involved in tumor development in these patients, with a particular focus on the involvement of immunosuppressive treatments.

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.

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 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.

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.

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.

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.