Reviews & Analysis

Optimal management of anemia in patients with end-stage renal disease on hemodialysis usually demands intravenous iron supplementation. Michael et al. review the current safety data for the nondextran intravenous iron formulation sodium ferric gluconate complex, and examine the emerging concerns related to use of intravenous iron, including the risks of infection, oxidative stress and cell toxicity.

If detected early, damage to the kidneys caused by medications can be reversed in most instances. Physician awareness of which drugs have pathogenic potential is therefore essential. This article synthesizes current knowledge of the mechanisms by which commonly used drugs induce renal injury. Comprehensive summary tables that present the drug types associated with each mechanism, clinical findings and recommended management strategies are included.

Transcriptome-based assessment of blood, urine or biopsy tissue could have a powerful impact on the management of renal transplants, with the potential to detect injurious mechanisms before graft injury is established. This Viewpoint article explores the promise held by transcriptomics and high-density microarrays, and examines the challenges of applying these new technologies in renal transplant recipients.

The plasma concentration of sodium ions normally exceeds the sum of the plasma concentrations of chloride and bicarbonate ions. Calculation of the resulting 'anion gap' can aid the diagnosis of various acid–base and electrolyte disorders. Michael Emmett discusses the utility of this approach, and highlights the potential disrupting factors which should be taken into account when interpreting anion gap calculations.

Maintaining cardiovascular stability while eliminating toxins is the challenge that confronts intensivists managing critically ill patients whose kidneys have failed. Generally treated with continuous venovenous hemofiltration or intermittent hemodialysis, evidence is emerging that prolonged dialysis at low flow rates has equivalent safety and efficacy in acute renal failure, plus the advantages of flexible treatment timing and reduced costs.

The mutations ofPKD1 and PKD2, and PKHD1, which cause autosomal dominant and autosomal recessive polycystic kidney disease, respectively, disrupt the function of polycystins and fibrocystin in tubular epithelial cells. The cellular consequences of these perturbations are reviewed here by Torres and Harris, with emphasis on the affected signaling pathways.

There is no specific treatment for kidney damage secondary to deposition of polymeric IgA. Nephrologists' opinions on the optimal management strategy for IgA nephropathy therefore vary widely, encompassing perturbation of the renin–angiotensin system, tonsillectomy, fish oil, steroids and cytotoxic agents. The data supporting these and other therapeutic options are presented in this critical analysis.

Recurrence of lupus nephritis after kidney transplantation is often regarded as rare, and transplantation of patients with end-stage renal disease secondary to this condition is common. Several studies, however, have reported a higher incidence of recurrence of lupusnephritis after renal transplantation than the 1–4% which is usually quoted. Weng and Goral discuss reasons for the variation in reported incidence of recurrent lupus nephritis and consider the potential clinical impact of recurrence.

The escalating burden of diabetic nephropathy is largely a function of the increased frequency of type 2 diabetes, which is associated with obesity and the metabolic syndrome. Prevention is dependent on elucidation of causal mechanisms. Here, Richard Johnson and colleagues present evidence for a mechanism that might form the basis of novel intervention strategies.

In this comprehensive review, Giuseppe Remuzzi and colleagues present a hypothesis for the pathophysiology of pre-eclampsia that unifies findings from a recent flurry of research. These new insights should spur the development of novel treatments for the hypertension and proteinuria that are hallmarks of this leading cause of fetal and maternal morbidity.

Does erythropoietin have the potential to ameliorate renal injury in humans? This article addresses this question in the context of our current understanding of the pathophysiology of acute renal failure. Recent findings from experimental models are presented, and their relevance to mechanisms of acute renal failure—including endothelial and tubular cell injury, and inflammation—are discussed.

In 1955, the Swiss hematologist Conrad von Gasser coined the term ‘hemolytic uremic syndrome’ to describe the combined symptoms of diarrhea, hemolytic anemia, thrombocytopenia and acute renal failure, which he had observed in five children. Since then, investigators have realized that some forms of hemolytic uremic syndrome can be attributed to genetic abnormalities in circulating and membrane-bound proteins that regulate the complement system. How do these abnormalities influence the course and outcome of the disease, and how should they affect its treatment?

Age-related decline in the capacity of the kidney to repair itself is a significant contributor to mortality associated with acute renal failure. In this well-balanced overview of renal and bone-marrow stem cells, Lloyd Cantley summarizes current knowledge and speculates on mechanisms of regeneration that have therapeutic potential.

Despite the implications of the term 'focal segmental glomerulosclerosis', subtypes of this form of idiopathic nephrotic syndrome are not always focal, segmental or sclerotic. Here, Alain Meyrier presents a comprehensive update of our understanding of the processes that underlie the development of variants of this condition, with emphasis on the unifying role of the podocyte.

Thiazolidinediones are synthetic agonists of peroxisome proliferator-activated receptors that have shown promise inin vitroand animal models of nephropathy. Encouraging early-stage data have also been generated in patients with diabetic nephropathy. Carol Pollock and colleagues outline what we know and what we need to find out before thiazolidinediones such as pioglitazone and rosiglitazone can fulfill their clinical potential.