Reviews & Analysis

Follow-up data from the RAVE trial have shown that rituximab is as effective as immunosuppression with cyclophosphamide followed by azathioprine in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis. Rituximab is likely to become the standard of care for many patients with ANCA disease. However, an individualized approach is needed to identify those who require more-intense or prolonged therapy.

Current guidelines recommend lowering blood pressure (BP) in patients with chronic kidney disease and hypertension. However, a new study suggests that achieving ideal systolic BP targets at the expense of low diastolic BP <70 mmHg is not advantageous for outcomes.

The glomerular endothelium is the first part of the glomerular filtration barrier that provides a barrier to albumin. In this Review, Simon Satchell describes the evidence for a role of the glomerular endothelium, and particularly the endothelial surface layer, in albumin handling. He also discusses the roles of podocytes and glomerular endothelial cells in glomerular homeostasis, and the therapeutic potential of targeting the endothelial surface layer in glomerular and vascular diseases.

A new study provides cogent evidence that fluid overload—measured using bioimpedance spectroscopy—promotes progression of chronic kidney disease (CKD). A prospective randomized trial is warranted to assess the effect of interventions to reduce fluid overload on disease progression in patients with CKD.

Accurate stratification of renal risk is important for the effective management of patients with type 2 diabetes. In a new study, Elley et al. report and validate a 5-year prediction model for the development of end-stage renal disease in patients with type 2 diabetes in primary care.

Multiple interventions can retard the progression or prevent the development of microvascular and macrovascular complications in patients with diabetes, but the effects of early glycaemic control seem to be longer lasting than those of blood pressure control. Cherney et al. now report that renin–angiotensin system blockade has sustained beneficial effects in patients with type 1 diabetes mellitus.

A new study by Turin et al. reports that proteinuria of increasing severity is associated with a faster rate of decline in estimated glomerular filtration rate (eGFR), regardless of eGFR at baseline. These findings support the use of proteinuria testing to identify individuals at risk of chronic kidney disease progression.

A new meta-analysis reports that intensive blood pressure lowering reduces the risk of kidney failure in patients with chronic kidney disease and albuminuria. However, the level of blood pressure control required for optimum protection of the cardiovascular and renal systems remains unclear.

Ralib et al. report that urine output (UO) <0.3 ml/kg/h for >6 h predicts a composite outcome of mortality and dialysis requirement in critically ill patients. Their findings validate UO as a marker of acute kidney injury, but raise the question of whether the diagnostic thresholds should be more stringent.

Cardiovascular mortality is very high in young patients with chronic kidney disease (CKD), and it has been suggested that patients with CKD exhibit a 'premature ageing' phenotype. This Review discusses data showing that uraemic toxins can drive vascular smooth muscle cell damage and phenotypic changes that promote vascular calcification. It also describes emerging data indicating that uraemic toxins may also promote DNA damage, which drives cellular ageing.

New data suggest that arteriovenous fistulas compared with prosthetic grafts may not be a superior predialysis approach to vascular access for haemodialysis in patients aged ≥80 years. However, the use of catheters as the first vascular access was associated with significantly increased mortality in these patients and should be avoided.

Renal fibrosis and anaemia are hallmarks of progressive chronic kidney disease (CKD). New evidence demonstrates that these conditions are intimately connected, as injury triggers the phenotypic transition of renal erythropoietin-producing cells into fibrogenic myofibroblasts. Strategies to reverse such a transition may hold promise to alleviate both anaemia and fibrosis in CKD.

An epidemic of chronic kidney disease of unknown aetiology has emerged in Central America and resulted in the highest rates of end-stage renal disease worldwide. New findings from the first renal biopsy study of patients with Mesoamerican nephropathy should help medical detectives to 'crack' the cause of this disease.

This article highlights the evolution in understanding of the podocyte slit diaphragm. Now appreciated as far more than a simple intercellular connection, the slit diaphragm controls the structure and function of the glomerular filtration barrier. However, several slit diaphragm properties remain unclear: its role in filtration, exact molecular structure, and the complex pathways initiated by this dynamic signalling hub.

Cardiac disease and renal disease are frequently accompanied by nonthyroidal illness, which can result in deterioration of cardiovascular and renal function via several pathways. In this Review, the authors discuss the hypothesis that nonthyroidal illness is a cardiorenal connector in the genesis and maintenance of the cardiorenal syndrome, and describe data from studies that have investigated the efficacy of thyroid hormone replacement therapy in patients with renal or cardiac disease.

Ezzelarab et al. report that regulatory dendritic cells administered prior to transplantation modulate alloimmunity and increase kidney allograft survival. This finding provides the first evidence of the immunosuppressive efficacy of modified dendritic cells in a stringent pre-clinical primate model, offering hope that long-term immunosuppression of transplant recipients could be minimized or avoided.

Amyloid formation and deposition results in a progressive disturbance of organ function. The kidneys are frequently involved in systemic amyloidosis and, without treatment, the disease is usually fatal. In this Review, the authors discuss amyloid pathophysiology, diagnosis, and current and future therapeutic strategies for the various systemic amyloidosis syndromes.

In Africa, the burden of treating the more common and widespread communicable diseases such as HIV/AIDS and tuberculosis has meant that treatment of kidney disease has been a low priority. In this Review, the authors describe the epidemiology of acute kidney injury and chronic kidney disease in Africa. They discuss the unique problems faced across this continent and the programmes that have been put in place to attempt to tackle these problems.

Ravani et al. report that rituximab is a safe and effective steroid-sparing and calcineurin-inhibitor-sparing agent in 46 children with idiopathic nephrotic syndrome over a median follow-up of 3 years. What is the risk-to-benefit profile of rituximab compared to that of the other available drugs for treating this disease?

The optimal dialysate bicarbonate concentration is one that prevents acidosis at the beginning of the next dialysis session while avoiding postdialysis alkalosis. Few studies have assessed the effect of different dialysate bicarbonate levels on patient outcomes, but Tentori et al. now report that high dialysate bicarbonate concentrations may contribute to adverse outcomes.