Reviews & Analysis

The slit diaphragm spans podocyte foot processes, effacement of which is a feature common to all glomerular diseases. Recent work in nephrotic syndrome and focal segmental glomerulosclerosis has led to identification of mutations in several gene products that function at the slit diaphragm, such as nephrin, Neph1 and podocin. Johnstone and Holzman predict that these molecular insights will facilitate disease classification and optimization of therapy.

Selective cyclo-oxygenase 2 inhibitors (coxibs) were designed to provide effective analgesia without the gastrointestinal toxicity of classical, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Concern has arisen, however, about the cardiovascular and renal safety of coxibs. In this Viewpoint, Matthias Hermann and Thomas F Lüscher examine the differences among these agents in their effects on sodium excretion, glomerular filtration rate and blood pressure, and provide their overall recommendation for use of these agents.

Although renal dysfunction can have a profound effect on the pathogenesis of cardiovascular disease, current guidelines for the management of hyperlipidemia in patients with chronic kidney disease (CKD) were formulated in the absence of data on cardiovascular and cerebrovascular outcomes in this population. Considering the individual stages of CKD, authors from the University of Würzburg, Germany, analyze data from the 4D trial and other studies, and attempt to answer the question of when hyperlipidemia should (or should not) be treated in patients with CKD.

Introduced in the late 1990s for non-Hodgkin's lymphoma, the anti-CD20 monoclonal antibody rituximab has had anecdotal success in several renal settings. Here, Salama and Pusey compile and evaluate the data supporting use of rituximab to manage post-transplantation lymphoproliferative disorder, graft rejection, and ABO- and HLA-incompatibility. The drug's potential utility in autoimmune conditions that affect the kidney, including focal segmental glomerulosclerosis and systemic lupus erythematosus, is also assessed.

Production of nitric oxide (NO) is reduced in chronic kidney disease and end-stage renal disease. Data support the conclusion that low NO levels, probably a function of perturbed endothelial synthesis, contribute to progressive kidney dysfunction. Chris Baylis outlines the mechanisms by which NO deficiency can develop in renal disease states, and discusses the potential for developing new treatments by manipulating NO biosynthetic pathways.

Primary aldosteronism is found in about one-tenth of people with hypertension. Following diagnosis, effective treatment is based on identification of the specific subtype of this condition. Of the various causes underlying primary aldosteronism, bilateral idiopathic hyperplasia and aldosterone-producing adenoma are the most common. In this Review, the authors describe the optimal approaches to detection and management of subtypes of aldosterone hypersecretion.

Terry Strom and Manikkam Suthanthiran present the results of studies investigating the potential of transcriptional profiling, based on both polymerase chain reaction and DNA array technologies, to identify renal allograft rejection from allograft biopsy specimens, blood and urine sediment. They argue that in future, such analysis will function not only as a surrogate for the invasive biopsy procedure, but could also have the capacity to provide predictive, diagnostic, and prognostic information.

The cortex and medulla of the kidney are believed to exist on a tightrope between normal function and hypoxia. The contributions of cortical and medullary hypoperfusion to hypertension have been widely investigated. In this Viewpoint, Thomas Pallone distills current knowledge on the roles of nitric oxide and reactive oxygen species in this setting, and speculates on the implications for future treatment of hypertension.

In critical care units, acute renal failure is less common in premature infants than in more mature individuals. Recent studies indicate a role for the heat shock response in this clinical phenomenon. Distilled here, these new data could lead to strategies for identifying patients at greatest risk of developing acute renal failure.

After outlining the mechanisms of phosphorous homeostasis—in which the kidney has a central role—Amanzadeh and Reilly explain how perturbation of this regulatory system can lead to hypophosphatemia. The authors then critically evaluate the clinical sequelae of this condition, and round out their review with advice on managing hypophosphatemia of varying severity in different patient populations.

The author comprehensively reviews novel data on the molecular mechanisms that underlie progression of kidney damage secondary to urinary tract obstruction. Encompassing inflammation, tubular cell apoptosis and interstitial fibrosis, the potential for the new findings to give rise to predictive biomarkers and molecular therapies for this leading cause of pediatric chronic renal failure is explored.

Elevated blood pressure is a strong and independent risk factor for the development of end-stage renal disease. Various investigators have examined whether all renal diseases are similarly sensitive to high blood pressure and whether they benefit similarly from antihypertensive therapy. Reviewing data from different renal disease populations, authors from the Medical University of Silesia provide their recommendations on the optimal blood pressure goals for slowing progression of renal insufficiency.

Currently, there is little that can be done to treat fibrosis of the kidney. Recent advances in renal pathophysiology are yielding insight into the derivation of fibroblasts and their role in this inflammatory disease. Eric Neilson reviews this progress, catalogs the new targets for intervention that have been identified, and asserts that the future for clinical management of fibrosis is bright.

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.