Review Articles in 2006

This Review integrates discussion of well-established mechanisms that are known to underlie the 'fetal origins hypothesis' of hypertension with examination of mechanisms for which data continue to emerge. Set in the context of implications for public health, the authors suggest that monitoring the blood pressure, renal function and body weight of at-risk children might help to reduce the likelihood of kidney and cardiovascular disease developing in later life.

It is essential that community-based nephrologists and primary care physicians, who are increasingly involved in the management of stable renal allograft recipients, are familiar with new-generation immunosuppressive drugs. This comprehensive article by Arjang Djamali and colleagues is a guide to the pharmacokinetics, dosing, drug–drug interactions and adverse effects of the mainstays of modern immunosuppression; calcineurin inhibitors, antimetabolites, mTOR inhibitors and corticosteroids.

It is estimated that up to 30% of people who regularly receive hemodialysis for kidney failure suffer from a depressive disorder. Depression can compromise treatment compliance, and modulate the immunological and nutritional status of patients. In this thorough and balanced overview, the authors explore this understudied issue, drawing attention to the problems associated with detection of depression and effective management in hemodialysis populations.

Seven single gene mutations are known to cause hypertension, generally by affecting electrolyte transport in the distal nephron, or synthesis or activity of mineralocorticoid hormones. These relatively uncommon disorders should be considered when young patients with a family history of high blood pressure present with severe or refractory hypertension. This article guides clinicians through identification of these defects, their associated laboratory findings, and recommended treatments.

This short article is an introduction to the histology of damage to transplanted kidneys caused by active BK virus infection. Aimed at trainee pathologists and nephrologists wishing to enhance their understanding of the histological basis of the diseases they manage, this beautifully illustrated paper describes the key features, differential diagnosis and clinical implications of this increasingly frequent complication.

Are polymorphisms of the G protein-coupled receptor kinase GRK4 the key to developing new tools for the diagnosis and management of essential hypertension? Here, Felder and Jose explore the therapeutic potential of manipulating this protein, which regulates the activity of the dopamine-1 receptor. The role of GRK4 is set in the context of the contributions of the dopaminergic and renin–angiotensin systems to the pathogenesis of hypertension.

Authors from the University of Heidelberg present a provocative and comprehensive Review of the issues involved in management of hypertension in patients with type 2 diabetic nephropathy. After examining the relationships between the renin–angiotensin system (RAS), proteinuria and hypertension, Ritz and Dikow focus on controversies such as the effect of RAS blockade beyond blood-pressure reduction, and optimal doses of drugs that inhibit RAS.

When stimulated by pathogens or endogenous ligands, Toll-like receptors (TLRs) initiate production of myriad cytokines. Long known to reside on cells of the innate immune system, 10 of 11 TLRs have now been shown to be expressed in human kidney. Data supporting a role for these renal TLRs in a variety of conditions, including sepsis-induced acute renal failure, ischemic injury, and rejection of allografts, are presented.

Here, the concept of a self-perpetuating cyclical interaction between outcomes of oxidative stress (such as production of reactive oxygen species and depletion of antioxidants) and inflammatory mediators (such as cytokines), driving initiation and progression of hypertension, is presented. Experimental evidence to support operation of such a cycle is outlined, and the therapeutic implications of targeting the interactions therein are discussed.

The ideal vascular access for hemodialysis would have a long functional life, facilitate blood flow sufficient to achieve dialysis prescription, and have a low rate of associated complications. This Review assesses the success with which available forms of access fulfill these criteria. The discussion is set in the context of the 2000 K/DOQI dialysis access guidelines and data published in the past 5 years.

Few studies have specifically addressed treatment of cardiovascular disease in kidney transplantees. As such, extrapolation from trials in other patient populations forms the basis for current management regimens. Here, the etiology of, and major risk factors for, cardiovascular complications in renal transplant recipients are reviewed. Evidence for risk factor-specific interventions for left ventricular hypertrophy, congestive heart failure and ischemic heart disease in this population is also appraised.

Parasites are an under-recognized cause of serious complications following organ and tissue transplantation. This comprehensive overview of the infectious species most commonly encountered in immunocompromised graft recipients—including protozoa, such as malaria and leishmania, and nematodes—aims to increase clinicians' index of suspicion when presented with pyrexial illness in this patient population. Routes of infection, key clinical characteristics, diagnostic techniques and treatments are discussed.

Here, Mak and colleagues shed light on the molecules associated with acidosis and inflammation that contribute to the development of nutritional abnormalities in patients with end-stage renal disease. Targeting these hormones, which act on the hypothalamic melanocortin system, ameliorates experimental cachexia. Using these new insights as the basis for developing human therapies should help to reduce cachexia-related mortality in the uremic population.

Authors from the Autonomic Dysfunction Center at Vanderbilt University present an overview of what is known about this poorly understood and often overlooked form of blood pressure dysregulation. The definition, pathophysiology, diagnosis and treatment of orthostatic hypertension, and conditions associated with it, are touched on. Through their comprehensive analysis, Fessel and Robertson detect the gaps in knowledge that should direct future research.

Elucidating protein profiles that can provide diagnostic and prognostic information is the aim of an increasing number of proteomics projects. This daunting task is being advanced by the continual improvement of high-throughput technologies. Here, Michael Goligorsky and colleagues introduce us to these techniques, and describe how they might be applied to renal tissues and urine. Data from early studies of diseases of native and grafted kidneys are presented.

Neutrophils, lymphocytes, macrophages and dendritic cells mediate the inflammatory response which damages the kidney during ischemia–reperfusion. This Review provides a concise summary of the complex hypoxia-induced interactions between these components of the immune system. The role of the renal-circulation regulator adenosine and its cellular receptors is then discussed, and the potential for adenosine agonists to ameliorate ischemia–reperfusion injury examined.

This short article is an introduction to the histology of damage to transplanted kidneys caused by the immunosuppressants tacrolimus and ciclosporin. Aimed at trainee pathologists and nephrologists wishing to enhance their understanding of the histological basis of the diseases they manage, this beautifully illustrated paper describes the key features, differential diagnosis and clinical implications of nephrotoxicity induced by calcineurin inhibitors.

The existence of several different definitions of acute renal failure makes it difficult to determine the true epidemiological characteristics of this condition. Nonetheless, there have been notable variations in its epidemiology during the past few decades. Norbert Lameire and colleagues present an overview of these changes and their causative factors, including geography, patient setting and ageing populations.

By integrating discussion of responses to HLA and non-HLA donor antigens in transplantation, and fetomaternal microchimerism, Pierre Ronco and colleagues have produced a clear and concise overview of alloimmune processes underlying nephropathy of both grafted and native kidneys. The article describes the authors' discovery of a novel form of alloimmunization which causes congenital embranous nephropathy—transfer of antibodies against neutral endopeptidase from mother to fetus.

The therapeutic potential of statins might extend beyond lipid lowering in cardiovascular disease. Experimental and clinical data to support this assertion are assessed here by authors from the University Hospital of Geneva, with an emphasis on the capacity of drugs of this class to modulate immune processes which affect the kidney during progression of chronic renal disease and transplantation.