Reviews & Analysis

Lower blood concentrations of protein-bound solutes have been directly linked to better outcomes in patients on dialysis. Studies indicate that clearance of protein-bound solutes is more efficient in patients on hemodialysis than in those on peritoneal dialysis; however, paradoxically, the circulating levels of these solutes are lower in patients on peritoneal dialysis. Vanholder and colleagues consider possible explanations for this discrepancy, such as differences in intestinal generation or metabolism of these molecules.

Studies have shown that rituximab, a chimeric monoclonal antibody that targets the CD20 antigen of B cells, might be a valuable alternative to current therapies for idiopathic membranous nephropathy. In this Viewpoint article, Ruggenenti and colleagues discuss the use of rituximab in idiopathic membranous nephropathy and reason that titrating rituximab therapy to CD20⁺cell counts might be an effective way of limiting patient exposure to rituximab without reducing the efficacy of treatment, and would also substantially reduce treatment costs.

The role of aldosterone in the progression of kidney dysfunction, via its actions on mineralocorticoid receptors, is increasingly recognized. The authors of this Viewpoint outline the beneficial effects that have been seen in animal and human studies of mineralocorticoid receptor blockade in various forms of kidney disease. They predict that low daily doses of the aldosterone blocker spironolactone—an inexpensive, generic medication with few and easily recognizable adverse effects—might one day become the renal equivalent of 'baby' aspirin.

Here, Cohen and Kimmel attempt to counter the arguments presented by Lynda Szczech in the preceding Viewpoint. They point out that HIV-associated kidney disease exists in various forms that have different treatment requirements and that renal biopsy is necessary to establish the exact diagnosis. They argue, furthermore, that the efficacy and safety of highly active antiretroviral therapy against HIV-associated nephropathy is questionable and that such treatment should not, therefore, be initiated empirically.

This Viewpoint attempts to counter the arguments presented by Cravedi et al. in this issue of Nature Clinical Practice Nephrology. Although β-cell islet transplantation is not yet a widely viable treatment for type 1 diabetes, AM James Shapiro argues that the procedure's shortcomings are not insurmountable and that now is not the time for a moratorium on clinical research. Enhancing the mass of the initial islet engraftment, which would alleviate many of the present challenges, could be achieved in ongoing trials, and remarkable progress with xenotransplantation and human embryonic stem cells foreshadows the possibility of a renewable islet cell source.

Should renal biopsy be performed in all patients with both HIV infection and kidney disease? In this Viewpoint, Dr Szczech argues that, given its efficacy against conditions like HIV-associated nephropathy, antiretroviral therapy should be implemented before biopsy is considered. Only when suppression of viral replication fails to improve renal function does the case for biopsy become more compelling. In any event, much as with HIV-negative patients with renal disease, empiric therapy should be implemented before renal biopsy is undertaken.

The enthusiasm for pancreatic β-cell islet transplantation that followed the introduction of the 'Edmonton protocol' in 2000 has been tempered by evidence that the immunosuppressants used in the protocol might be nephrotoxic and that the resultant insulin independence is only short-term in most patients. Cravedi and colleagues analyze the risks and benefits of islet transplantation and argue that it should not be regarded as a general alternative to insulin replacement therapy for patients with type 1 diabetes mellitus.

The development of a wearable device that can replace conventional dialysis in patients needing chronic renal replacement therapy is not as far-fetched as it once was. Ronco et al. describe technological achievements, propose future research directions and discuss the clinical, technical and socioeconomic reasons for continuing the push to realize the wearable artificial kidney.

Various strategies have been considered in attempts to improve the outcomes of dialysis patients. Such strategies include increasing dialysis dose, using alternative depuration methods, changing dialysis schedules and focusing on preventing or treating specific co-morbidities and complications. In this Viewpoint, Andreas Pierratos discusses the first three strategies, and concludes that he believes that a paradigm shift, a disruptive change-in the form of daily home nocturnal hemodialysis-is needed to improve dialysis outcomes.

Lymphocyte depletion has recently been adopted to allow immunosuppression minimization or even to achieve donor-specific tolerance in transplant recipients. The long-term aim of such therapy is to minimize toxic effects associated with standard immunosuppression, but this beneficial effect is offset by the potential toxicity of the global depletion of lymphocytes and, in some cases, monocytes and neutrophils. This Viewpoint summarizes current data on depletion strategies in kidney transplantation, typically in the setting of induction treatment.

Inhibitors of vascular endothelial growth factor, such as bevacizumab, are a promising approach to the treatment of tumors and other angiogenesis-dependent conditions. However, it is becoming increasingly obvious that these drugs can have serious adverse effects including proteinuria, hypertension and thrombotic microangiopathy. This Viewpoint evaluates current evidence to argue that these adverse effects are probably elicited by inhibition of nitric oxide production in the renal vasculature.

Multifactorial approaches to the treatment of type 2 diabetes mellitus have proven more effective than any individual intervention alone in reducing the risk of cardiovascular complications. As the spread of diabetes and obesity accelerates worldwide, unhindered by lifestyle modification approaches, the authors of this Viewpoint propose an aggressive multifactorial strategy for treating patients who have one or more risk factors for the metabolic syndrome in an effort to prevent or delay the onset of diabetes.

Although low-molecular-weight heparins (LMWHs) have largely replaced unfractionated heparin for the treatment of deep vein thrombosis and pulmonary embolism in the general population, sufficiently powered clinical studies on the use of LMWHs in patients with renal impairment are lacking. In this Viewpoint article, Gallieni and colleagues discuss reasons why LMWHs should be used with caution, at present, in patients with chronic kidney disease.

According to the Kidney Disease Outcomes Quality Initiative guidelines, estimated glomerular filtration rate can be used to diagnose chronic kidney disease. The authors of this Viewpoint argue, however, that reliance on estimated glomerular filtration rates alone encourages an erroneous disregard of age, gender and other evidence of kidney disease, such as proteinuria. Consequently, mandatory reporting of estimated glomerular filtration rate leads to misdiagnosis of chronic kidney disease and to the unhelpful referral of healthy individuals to nephrologists.

A relationship between disturbed lipid metabolism and kidney disease was first postulated in 1858. Over the years, many animal studies have indicated that lipids have a pathophysiologic role in renal disease. The authors of this Viewpoint describe the possible mechanisms through which lipids might promote the progression of glomerular and tubulointerstitial diseases.

This, the second of two opposing Viewpoints, presents the case for the use of cinacalcet for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease who are not receiving dialysis. The authors assert that cinacalcet effectively reduces serum parathyroid hormone level in this setting, and that any adverse effects of the drug on calcium or phosphorus levels can be managed by monitoring and treating patients accordingly.

In the first of two opposing Viewpoints, Daniel W Coyne questions the use of cinacalcet to treat secondary hyperparathyroidism in non-dialysis-dependent patients with chronic kidney disease. He highlights the absence of FDA approval and the lack of published data for cinacalcet in this setting. Cinacalcet does not, he argues, address a universal pathophysiologic feature of secondary hyperparathyroidism; in addition, it has considerable adverse effects.

The authors of this Viewpoint argue that the currently used definitions of cardiorenal syndrome fail to take into account the complex bidirectional nature of the relationship between the heart and kidneys. They propose a new classification of the condition, comprising five subtypes that are distinguished on the basis of the primary and secondary pathology and its chronology. Examples of each subtype are provided.

In the late 1990s, a series of papers described the isolation and propagation of calcified, nanometer-sized structures from calf serum and diseased tissues. These findings prompted researchers at the Mayo Clinic, Rochester, MN to investigate the possibility that transmissible biologic nanoparticles could be responsible for pathologic calcification in the kidneys and blood vessels. Here, a member of the Mayo group summarizes the research to date in this exciting field.

Reports from Japan indicate that renal artery embolization holds promise for relieving the 'mass effect' symptoms of autosomal dominant polycystic kidney disease. Authors from the University of Maryland School of Medicine compare the safety and efficacy of this procedure with that of the techniques more widely used to relieve the symptoms of autosomal dominant polycystic kidney disease, including nephrectomy, cyst marsupialization and cyst decortication.