Reviews & Analysis

A new meta-analysis shows a strong association between low levels of preformed donor-specific HLA antibodies (DSAs) detected using sensitive solid-phase assays and an increased risk of renal allograft failure. These findings have important implications for stratifying patients with DSAs for organ allocation and for the use of alloantigen desensitization therapies.

According to new data from Hirsch et al., the risk of polyomavirus BK (BKV) viraemia in kidney transplant recipients is increased by high steroid exposure early after transplantation, treatment with tacrolimus rather than ciclosporin A, older donor age and male gender. However, confounding of results due to variations in immunosuppressive drug exposure cannot be excluded.

Hsu et al. report a progressive increase in the incidence of dialysis-requiring acute kidney injury (AKI) and associated deaths in the USA between 2000 and 2009. As with chronic kidney disease, a concerted campaign to increase awareness and alertness of AKI is urgently required. We must prevent “kidney attack”.

Guidelines are painted with broad strokes and cannot possibly cover complex situations that emerge in the care of people with chronic kidney disease and multiple illnesses. The authors of the recent KDIGO blood pressure guidelines should be congratulated on urging us to individualize therapy especially in situations where the evidence base is thin.

Bardoxolone methyl showed promising results in initial studies in patients with type 2 diabetic kidney disease, but a phase III trial was terminated early in October 2012 due to adverse effects and increased mortality. Can adverse findings of analogues of bardoxolone methyl in an animal model explain the human findings?

The aetiology of primary focal segmental glomerulosclerosis has proven elusive. Recent data implicates the soluble urokinase-type plasminogen-activator receptor (suPAR) as the circulating permeability factor in the majority of patients with this condition. These exciting findings may dramatically influence the future diagnosis and management of this often resistant glomerular disease.

Many noninsulin glucose-lowering agents have pharmokinetic and elimination profiles that preclude their use in patients with reduced renal function. However, several of these drugs can be used safely in patients on dialysis and should be considered by physicians. In this Review, the authors provide a guide to the use of noninsulin hypoglycaemic agents for the management of diabetes in patients receiving dialysis and also discuss the monitoring of glycaemic control in these patients.

Podocytes, a key component of the glomerular filtration barrier, adhere tightly to the glomerular basement membrane (GBM) through the actions of extracellular ligands within the GBM, transmembrane podocyte adhesion receptors, and intracellular linker proteins. This Review summarizes recent advances in our understanding of the cell biology and genetics of podocyte adhesion with a focus on its functional relevance in physiology and disease.

Rituximab offers an alternative approach to current immunosuppressive therapies for patients with difficult-to-treat, steroid-dependent nephrotic syndrome. Rituximab therapy has been shown to induce and maintain remission in these patients; however, most data are derived from anecdotal reports or case series. This Review provides an overview of available data on the safety and efficacy of rituximab in the treatment of paediatric and adult patients with nephrotic syndrome.

Cellular regeneration—the repair of portions of the existing nephron after tubular damage—is conserved in all animal species. By contrast, nephron neogenesis is present in lower branches of the animal kingdom, but not in adult mammals. Converging evidence suggests that a renal progenitor system is present in the adult kidney across different stages of evolution. Here, the authors look at renal regeneration from an evolutionary perspective and suggest possible explanations for the differences between animals.

Advances in molecular genetics and genomic science are improving our understanding of the molecular basis of nephrotic syndrome. However, the availability of genetic testing in the management of nephrotic syndrome poses unique challenges for clinicians in terms of who to test and how best to use the information obtained. Here, the authors present their collective opinion on the clinical indications for and the utility of genetic testing in monogenic nephrotic syndrome based on the evidence available to date.

The year 2012 brought a continued harvest of new findings of relevance to glomerular biology and disease. Progress in glomerular disease has continued, although our understanding of disease processes continues to extend much further than our ability to intervene effectively.

2012 saw the publication of four important trials investigating the choice of fluid therapy in patients suffering from critical illness or undergoing major surgery. These studies pave the way for more evidence-based administration of fluid in such patients.

During 2012, an observational study confirmed the high risk of cardiovascular disease ascribed to chronic kidney disease (CKD) and again raised the question of whether CKD should be considered a cardiovascular disease risk equivalent. Several other studies evaluated methods to mitigate cardiovascular risk in CKD. The results of these studies have advanced the field but have also raised more questions.

Patients with end-stage renal disease typically receive three 3–4 h haemodialysis sessions per week. Although available data from well-powered randomized trials are limited, studies published in 2012 provided new evidence that haemodialysis regimens with longer treatment times and/or a higher frequency of sessions might reduce the high morbidity and mortality of patients on maintenance dialysis.

2012 saw the classification of the systemic vasculitides revised. Genetic studies showed that granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are different diseases with aberrant immune responses to different autoantigens. B-cell depletion with rituximab also acquired a primary role in the treatment of GPA and MPA, as well as in cryoglobulinaemic vasculitis.

This Review discusses the concept of Ras-related C3 botulinum toxin substrate 1 (Rac1)-induced activation of the mineralocorticoid receptor and highlights the available evidence for the roles of Rac1 and mineralocorticoid-receptor activation in cardiac and renal disease. The authors suggest that agents that regulate the activity of the Rac1-mineralocorticoid-receptor pathway could be novel therapeutic candidates for the treatment of chronic kidney disease and cardiac injury.