Review Articles in 2008

Recurrent orde novo glomerulonephritis is a common cause of post-transplantation proteinuria and long-term renal allograft loss. This primer, which is aimed at trainee pathologists and nephrologists who wish to enhance their understanding of the histological basis of the diseases they manage, provides an overview of the prevalence, risk factors, pathogenesis, clinicopathologic features, and clinical implications of recurrent and de novoglomerulonephritis in renal allografts. Treatment options are also briefly summarized.

Interest in endogenous digitalis-like factors or 'cardiotonic steroids' has increased as a result of the identification of such factors in humans and the delineation of a mechanism by which these hormones signal through the sodium/potassium-transporting ATPase. The authors of this Review, who have both spent more than 20 years conducting research on this topic, examine the role of endogenous cardiotonic steroids in the pathophysiology of renal and cardiovascular disease. They also highlight potential therapeutic strategies involving modulation of cardiotonic steroids.

In this Review, Nosratola Vaziri endeavors to reconcile two apparently conflicting sets of evidence from patients with chronic kidney disease: the observational association between greater severity of anemia and increased risk of poor outcomes, and the increased risk of adverse outcomes in patients assigned to normal, rather than subnormal, hemoglobin targets in randomized clinical trials. The author focuses on data from basic and translational studies, which are often overlooked in the design and interpretation of clinical studies and in the formulation of clinical guidelines.

During recent years, awareness has been growing that oxalate is more than simply a metabolic waste product. Evidence is mounting that oxalate affects normal physiology, especially in the kidney. Here, authors from the Case Western Reserve University School of Medicine in Cleveland, OH, review the sources, excretion, and transport of oxalate, and examine the ways in which this molecule might contribute to nephrolithiasis.

Congenital anomalies of the kidneys and/or lower urinary tract are the major cause of childhood end-stage renal disease, and they can also present in adulthood. Kerecuk et al. summarize the anatomical and histological features of renal tract malformations, the best approaches to prenatal and postnatal diagnosis of these conditions, and the influence of genetic and environmental factors in their etiology. The utility of therapeutic intervention is also considered.

In this Review, participants in the 7^thInternational Fabry Nephropathy Roundtable, which was convened in Barcelona, Spain in June 2007, propose guidelines and recommendations for the diagnosis and management of Fabry nephropathy in adults. The roles of enzyme replacement and antiproteinuric therapy are emphasized. The authors suggest that these organ-specific recommendations could have a greater impact on clinical practice than general Fabry disease guidelines.

Patients with chronic kidney disease are known to develop metastatic soft-tissue calcification in tissues including the breast. Such calcifications in women could pose a problem for interpretation of mammograms. Authors from Staten Island University Hospital, NY review the available data on the prevalence and types of breast calcifications in women with chronic kidney disease, and discuss the utility of mammography in this setting.

Identification of the molecular pathways involved in renal pathophysiology can yield targets for intervention and aid tailored therapy. de Borst and colleagues provide an introduction to the tools that can be used to pinpoint genes involved in renal disease, including gene expression arrays, linkage analysis, association studies and animal models. Examples of genes that have been identified using these techniques are highlighted.

Since the first successful kidney transplantations were performed in the 1950s, understanding of the factors that improve graft outcome has advanced. Nevertheless, post-transplantation urinary tract infections continue to be a source of morbidity and graft failure. This article reviews urinary tract infection in the renal transplant recipient, covering epidemiology, etiology, prevention, presentation, investigations, diagnosis and management.

Renal disease predisposes sufferers to the development of many nonrenal complications. Prevention and early detection are key to minimizing the effects of infection, dyslipidemia, poor glycemic control and malignancy on patients with chronic or end-stage renal disease. This article includes several 'ready reference' summaries of how and when clinicians should vaccinate, monitor and treat patients so that complications are prevented.

Traditionally thought of as a primarily glomerular disease, evidence is accumulating to support early involvement of tubular and interstitial dysfunction in the development of diabetic nephropathy. This Review focuses on the role of chronic hypoxia in the tubulointerstitium as a major factor in the pathogenesis of diabetic nephropathy, and touches on the status of potentially beneficial clinical interventions.

Authors from the University of Vermont comment on the limitations of, and assumptions inherent in, the tools used by clinicians to detect and monitor acute kidney injury. After discussing the pitfalls associated with use of serum creatinine level and glomerular filtration rate, Solomon and Segal recommend means by which trial design can be improved while awaiting development and validation of more-accurate biomarkers of renal function.

It is important that clinicians from both developed and developing countries are familiar with the symptoms of tropical diseases. These conditions are endemic in many regions of the world, and immigration and travel are increasing the frequency with which patients present for care in the developed world. As malaria and leptospirosis are the most widely studied tropical diseases, Visith Sitprija from Thailand frames his presentation around these conditions.

Magnesium ions are essential to all living cells. As the second most abundant intracellular cation, magnesium has a crucial role in fundamental metabolic processes such as DNA and protein synthesis, oxidative phosphorylation, enzyme function, ion channel regulation, and neuromuscular excitability. After presenting an overview of magnesium homeostasis, the authors review the etiologies of hypomagnesemia, with an emphasis on hereditary causes.

The difficulties that are currently inherent in early diagnosis of acute kidney injury could be overcome by the introduction of biomarkers into routine clinical practice. Here, Bruce Molitoris and colleagues provide an update of the status of development of biomarkers for this indication. Transcriptomics, proteomics, and gene array and imaging technologies are just some of the methods being harnessed to drive the discovery process. Subsequent validation in high quality clinical trials will be essential.

Authors from India and the US have systematically reviewed the literature on acute kidney injury. Their comprehensive exploration of this condition in developing countries reveals surprising commonalities between areas that are influenced by seemingly disparate geographical, etiological and cultural factors. Determining the true incidence of acute kidney injury is key to increasing awareness of the problem in underdeveloped regions, and to initiation of efforts to prevent its occurrence.

Knowledge regarding this important system of renal chloride transporters has rapidly accumulated. A severe salt-losing tubulopathy—Bartter syndrome type III—develops when ClCKB is non-functional, whereas a common genetic variant of theCLCNKBgene results in salt-dependent hypertension. Disruption of the Barttin gene manifests as Bartter syndrome type IV with sensorineural deafness and an especially severe salt-losing phenotype. It is timely, therefore, to review the properties of these transporters.

Here, Dr Gubler describes the pathogenesis of disorders that affect components of the glomerular basement membrane, including type III and type IV collagen, laminin and fibronectin. Dr Gubler harnesses her considerable clinical experience to recommend diagnostic and management strategies for Alport syndrome, Pierson syndrome, nail–patella syndrome, benign familial hematuria/thin basement membrane nephropathy, and glomerulopathies caused by errant deposition of fibronectin and type III collagen.

Anemia is associated with exacerbation of both renal and cardiac disease. A considerable proportion of patients whose anemia is treated with erythropoietin do not respond, and the safety and efficacy of this therapy in people that have both chronic heart and kidney disease has not been proven. Overcoming erythropoietin resistance in this population must be predicated on understanding the processes that contribute to this state. These are reviewed here.