Review Articles in 2013

Chronic kidney disease (CKD) is associated with high levels of serum phosphate, fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH). FGF-23 acts in the kidney to induce phosphaturia and inhibit the synthesis of 1,25-dihydroxyvitamin D₃. Here, the authors discuss the pathogenesis of increased FGF-23 levels in secondary hyperparathyroidism associated with CKD.

The integration of omics analyses of primary glomerular diseases with data from clinical and histopathological studies is expected to advance our understanding of the molecular basis of these diseases and lead to improvements in diagnosis and treatment. Here, the authors provide an up-to-date overview of omics studies of primary glomerular diseases and suggest new approaches to further characterize their pathogenetic mechanisms, candidate genes, potential biomarkers and therapeutic targets.

Various equations have been developed for estimating glomerular filtration rate (GFR), but the issues surrounding GFR estimation are heavily debated. Although many guidelines now recommend the newer MDRD and CKD-EPI equations over the Cockcroft–Gault equation, these equations do fail to provide accurate estimates of GFR in some situations. This article discusses the development of the different equations and describes clinical situations in which the applicability of the equations is questioned.

Immunosuppressive treatment of patients with idiopathic membranous nephropathy is controversial because of the toxicity of the therapy and the variable natural course of the disease. In this Review, the authors discuss the 2012 Kidney Disease: Improving Global Outcomes guideline for the treatment of patients with idiopathic membranous nephropathy and highlight the remaining areas of uncertainty.

In this Review, the author discusses new insights into the pathogenesis of chronic kidney disease and describes a novel mechanism of ageing, both in the context of the fibroblast growth factor (FGF)–Klotho endocrine axis. In addition, the author proposes a new paradigm for dietary phosphate restriction in which phosphate restriction is started when serum FGF-23 level starts to rise, regardless of serum phosphate level.

The glomerular basement membrane (GBM) is the central layer of the glomerular filtration barrier and is situated between endothelial cells and podocyte foot processes. The functional importance of the GBM versus that of podocytes and endothelial cells for establishing the glomerular filtration barrier to albumin is still debated. This Review discusses the proposed mechanisms whereby the GBM serves as the major albumin barrier and describes two genetic kidney diseases that target GBM components.

Over the past 20 years, it has become clear that aldosterone exerts direct effects on the vasculature, heart and kidney beyond its effects on electrolyte handling in the distal tubule. In addition, mineralocorticoid-receptor activation has been shown to contribute to cardiovascular fibrosis and remodelling as well as to renal disease. This Review describes in detail the proinflammatory and profibrotic effects of aldosterone and mineralocorticoid-receptor activation in the heart, vasculature and kidney.

A growing number of studies in nephrology are focusing on biomarkers for chronic kidney disease (CKD). Here, Michael Shlipak and Erica Day describe biomarkers that are used to predict risk of developing CKD and outline the statistical methods that can be used to assess the performance of candidate biomarkers. The authors also provide a conceptual framework for interpreting the results of studies evaluating biomarkers of declining kidney function and incident CKD.

Alagille syndrome is caused by mutations inJAG1 and NOTCH2in the Notch signalling pathway. The disease presentation is highly variable, including multiorgan system involvement with renal and hepatic involvement. Recent studies suggest renal insufficiency can occur in isolation and suggests a role for impaired kidney development in patients with Alagille syndrome and chronic kidney disease.

Peritoneal dialysis is now the most commonly practiced form of home dialysis; however, a number of challenges must be overcome if use of this therapy is to continue to increase. In this Review, Simon Davies discusses the implications of evolving health-care trends—such as an ageing, increasingly multimorbid population—for the future of peritoneal dialysis, the main limitations of the therapy and the need for an integrated research effort to address these problems.

Patients with kidney disease are often exposed to high concentrations of iron as a result of the underlying pathological processes. Under these conditions, cellular mechanisms of iron metabolism respond to the changing iron concentrations, which can result in further pathological damage in the kidney. In this Review, the authors discuss mechanisms of iron metabolism under various pathological conditions and the potential role of modulating iron levels as a therapy for progressive kidney diseases.

Long-term peritoneal dialysis can lead to morphological and functional changes in the peritoneum. In this Review, Krediet and Struijk describe these changes and discuss how they can be assessed in clinical practice. They also discuss how the monitoring of some substances in peritoneal effluent, and the improved assessment of peritoneal transport parameters, may help detect such alterations at an early stage.

Vitamin D deficiency has been linked to a variety of disorders, including hypertension, type 2 diabetes and chronic kidney disease. A potential role for vitamin D deficiency in cardiovascular morbidity and mortality has also emerged. In this Review, the authors describe the evidence for an association between risk factors for cardiovascular disease and vitamin D status, and discuss the limitations of available data on vitamin D therapy in patients at increased risk of cardiovascular events.

Exciting advances in podocyte research over the past decade have provided new insights into the role of podocytes in the function of the glomerular filtration barrier. Here, the authors explain the importance of podocytes for the maintenance of an intact glomerular filtration barrier and prevention of albuminuria. They describe signalling pathways that regulate podocyte structure and function and discuss the potential of live podocyte imaging to further advance our understanding of podocyte biology.

The prevalence of increased blood pressure during sleep and a blunted sleep-time-relative blood pressure decline is high in patients with chronic kidney disease (CKD) and increases with disease severity. Here, the authors describe 24 h blood pressure variation and discuss data suggesting that bedtime dosing of hypertension medications might improve blood pressure control and reduce cardiovascular risk in hypertensive patients, including those with CKD.

Dialysis vascular access continues to be both a 'lifeline' and an 'Achilles' heel' for patients on haemodialysis. In this Review, the authors address some of the problems associated with vascular access, including dialysis access stenosis and arteriovenous fistula (AVF) maturation failure. They discuss the role of monitoring and surveillance, describe process of care pathways intended to increase AVF rates and decrease catheter use, and discuss novel therapies designed to reduce vascular access dysfunction.

Treatments administered to patients with primary IgA nephropathy (IgAN) and those with Henoch–Schönlein nephritis are largely based on opinion or weak evidence, and the recent KDIGO Clinical Practice Guidelines for Glomerulonephritis assigned low levels of evidence for the majority of recommendations and suggestions related to these two diseases. In this Review, Floege and Feehally describe an algorithm for structuring the treatment of IgAN depending on the clinical scenario, and discuss ongoing studies to investigate treatments.

Human kidneys produce more than 4 million litres of virtually protein-free primary urine in a lifetime, clearing more than 250,000 kg of plasma proteins in the process. The sieving process is accomplished by the glomerular filter and understanding this process is a prerequisite to understanding the pathogenesis of proteinuria. Here, the authors summarize the major models that have been proposed for the mechanisms of glomerular filtration and discuss their strengths and limitations, with special emphasis on their proposed model—the electrokinetic model.

Loss of renal function is associated with inflammation and immune system impairment, which results in an increased susceptibility to viral and bacterial infections, poor vaccination responses and an increased risk of malignancies in patients with end-stage renal disease (ESRD). Here, Michiel Betjes describes the effects of uraemia and renal transplantation on cells of the adaptive and innate immune systems. He also outlines the clinical implications of immune system impairment in patients with ESRD and discusses the concept of premature immunological ageing in these patients.

Dysregulation of angiogenesis and tubulointerstitial hypoxia is a common finding in renal disease. In this Review, the authors describe the process of vascular remodelling and its regulation by angiogenic factors and inhibitors. They explain the mechanisms by which angiogenesis and hypoxia in the kidney might lead to progression of renal disease and discuss the potential advantages and disadvantages of angiogenic and anti-angiogenic therapies as well as novel strategies to stabilize and generate healthy vasculature.