Volume 8 Issue 11, November 2012

Oral phosphate binder therapy is considered a 'tower of strength' in the ever-expanding armamentarium of drugs used to treat abnormal mineral metabolism in patients with chronic kidney disease (CKD) and use of these agents early in the course of CKD is gaining much interest. Recent data from a randomized controlled study by Block et al. challenge this strategy, raise doubts about its safety and indicate the need for additional studies of hard end points.

The new KDIGO anaemia guidelines represent a bold, sensible, and patient-centred approach to anaemia management in patients with chronic kidney disease. Recommendations regarding haemoglobin targets, blood transfusions, and erythropoiesis-stimulating agent therapy are provided, and individualizing the management of anaemia is emphasized.

Cell hypertrophy is the only mechanism by which podocytes can cope with increased functional demands, whereas other glomerular cells can adapt by cell proliferation. In the setting of systemically stimulated glomerular growth, a 'mismatch' of inadequate podocyte hypertrophy and overall glomerular growth may lead to podocyte loss and development of focal segmental glomerulosclerosis.

Several management guidelines for lupus nephritis have been published this year. All of the guidelines provide clear and consistent recommendations, but although evidence-based, many of the recommendations are not supported by high-quality clinical data. The guidelines reveal these evidence gaps and are thus an important roadmap for future lupus nephritis clinical research.

Atypical haemolytic uraemic syndrome (HUS), Shiga toxin-producingEscherichia coli-associated HUS and thrombotic thrombocytopaenic purpura are diseases characterized by microvascular thrombosis, with subsequent dysfunction of affected organs. In this Review, the authors discuss data indicating that complement dysregulation is a common pathogenetic effector of all three diseases, and describe the emerging evidence indicating that targeting complement may effectively treat these disease entities.

Improved understanding of the role of complement in the pathogenesis of a number of glomerular diseases has led to progress in disease classification and treatment. In this Review, Bomback and Appel re-examine the previous classification schemes for membranoproliferative glomerulonephritis (MPGN) and discuss the role of complement in the various MPGN lesions including the C3 glomerulopathies. In addition, they discuss the pathogenesis, diagnosis, treatment, and prognosis of the C3 glomerulopathies.

Here, Zuber et al., on behalf of the French Study Group for aHUS/C3G, discuss the role of eculizumab in the treatment of atypical haemolytic uraemic syndrome (aHUS). They review data from case reports and preliminary data from prospective trials, present their opinions, and describe issues that require further study. In addition, they discuss the potential use of eculizumab in C3 glomerulopathies.

Shiga toxin-producingEscherichia coli-associated haemolytic uraemic syndrome (STEC-HUS) is associated with renal and neurological injury. This Review summarizes the pathophysiology and clinical presentation of STEC-HUS and its acute and long-term effects on the kidney and central nervous system. The authors also describe the experience of a single centre that was affected by the STEC-HUS outbreak in Germany in 2011.

Much progress has been made in understanding the processes underlying antibody-mediated rejection (AMR) of transplanted organs. In this Review, the authors discuss the role of the complement system in acute and chronic AMR, with specific emphasis on renal transplantation, and describe studies demonstrating that blockade of terminal complement activation can prevent AMR in sensitized renal transplant recipients.

The complement system comprises a complex network of plasma proteins that cooperate in the defence against pathogens and the maintenance of tissue homeostasis. Although a role for complement in renal disease has long been recognized, increasing understanding of the mechanisms by which complement mediates renal injury has led to the development of strategies by which complement may be targeted to prevent renal disease and its associated complications. This focus issue on targeting complement in renal disease contains five Reviews written by experts in the field, describing the mechanisms by which complement deregulation causes kidney disease, how improved understanding of complement has resulted in the reclassification of renal disease, and potential treatment strategies to target complement in renal disease.