Reviews & Analysis

This article reports on a case of biopsy-proven nodular glomerulosclerosis in a patient with progressively worsening renal function, metabolic syndrome, but no evidence of diabetes. The authors conclude that screening patients with the metabolic syndrome—even those without diabetes—for evidence of impaired renal function and treating eventually detected albuminuria could help prevent progressive kidney disease and reduce the associated morbidity and mortality risks.

Acute phosphate nephropathy has emerged as an important complication of bowel preparation with oral sodium phosphate solution for colonoscopy. Retrospective studies have revealed that acute kidney injury occurs in 1–4% of individuals exposed to oral sodium phosphate. This Review outlines the presentation, risk factors and pathogenesis of acute phosphate nephropathy. The author proffers several recommendations for minimizing the renal risks of oral sodium phosphate.

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.

In this Case Study, Iwatani and colleagues describe two cases of valvular injury associated with noninfective endocarditis in patients with proteinase 3 antineutrophil cytoplasmic antibody-associated glomerulonephritis. Diagnosis, treatment and management of such cases is discussed, and the importance of distinguishing between noninfective and infective endocarditis is emphasized.

This Review analyzes the changing face of acute kidney injury in children in terms of etiology, incidence, diagnosis, treatment and long-term outcomes. The evidence base for conservative management of pediatric acute kidney injury (with agents such as diuretics, nesiritide and fenoldopam) is assessed, and the author offers advice on the optimal timing and modality of renal replacement therapy.

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.

This Review will help physicians to make the best case-by-case decisions when treating the three most common types of primary glomerulonephritis that progress to end-stage renal disease—membranous nephropathy, focal segmental glomerulosclerosis and IgA nephropathy. The authors systematically assess the benefits of reducing proteinuria in each of these diseases, and then place these benefits in the context of the early and late adverse effects of currently available therapies.

The role of antineutrophil cytoplasmic antibodies (ANCA) in the development of the pauci-immune vasculitide Churg–Strauss syndrome is unclear. Chemmalakuzhy et al. report the case of a 36-year-old man diagnosed with Churg–Strauss syndrome, whose presentation was notable for two atypical features: first, the absence of asthma and second, the presence of glomerulonephritis in the absence of ANCA. The latter observation challenges current thinking about the role of ANCA in the pathogenesis of the syndrome.

This Review sets out the case for updating the nomenclature of inherited salt-losing tubulopathies. The author argues that the so-called 'Bartter-like syndromes' constitute a diverse group of diseases whose only common feature is hyperaldosteronism secondary to a salt leak along the distal nephron. Since there is considerable phenotypic overlap between some of these syndromes, he outlines a more logical classification based on the exact location of the defective ion transporter or channel in the distal nephron.

The blood-pressure response to antihypertensive medications varies between ethnic groups. Whether ethnicity determines the outcomes of patients with hypertensive kidney disease is less clear. Here, authors from the US examine key ethnic variations in hypertensive chronic kidney disease and proffer their pharmacologic and lifestyle recommendations for blood-pressure control in this setting, with an emphasis on African Americans. The authors highlight the need for adequate representation of minority populations in future studies, in order to improve the evidence base for these recommendations.

Juxtaglomerular cell tumors usually occur during adolescence and early adulthood and are generally deemed benign. Beaudoin et al. report the case of a 51-year-old woman with a juxtaglomerular cell tumor of large size (9.8 cm versus the usual 2–3 cm), which showed histological signs of vascular invasion. Although no other evidence of malignancy was found, this case suggests that adult patients with large juxtaglomerular cell tumors should undergo follow-up after nephrectomy to enable detection of tumor recurrence and metastasis.

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.

Proteinuria and the underlying glomerulosclerosis seem to be reversible. Could such reversal be achieved by targeting endothelin via the ET_Areceptor? This Review begins with a summary of the mechanisms involved in the development of glomerulosclerosis—particularly those responsible for podocyte injury—and continues with an evaluation of the growth-promoting and vasoconstricting properties of endothelin. Finally, the findings of preclinical and clinical studies of endothelin receptor antagonists in proteinuric renal disease are summarized.

Considerable progress has been made over the past few years in understanding the pathogenesis of pre-eclampsia. In particular, the contribution of the circulating antiangiogenic factors soluble fms-like tyrosine kinase 1 and endoglin to the vascular and glomerular dysfunction of pre-eclampsia has been recognized. Inspired by these findings, Alexandre Hertig and colleagues from France, the US and Switzerland propose an updated and standardized protocol for the post-delivery follow-up of women with pregnancy-induced hypertension or pre-eclampsia.

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.

Dialysis units are facing a growing number of patients who disrupt the smooth functioning of the unit and even jeopardize the health and safety of other patients and staff. Here, authors from West Virginia University outline a set of ethical principles that can assist dialysis staff to deal with difficult or disruptive patients while meeting their ethical obligations to other patients. These principles can also be used to identify the limited situations in which involuntary patient discharge from a dialysis unit is ethically justified.

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.