Review Articles in 2009

Intravenous fluids are widely administered to patients who have, or are at risk of, acute kidney injury (AKI), but deleterious consequences of overzealous fluid therapy are increasingly being recognized. This Review describes the problems of fluid management in acquired AKI, and discusses the need to balance the competing needs of adequate fluid resuscitation, the avoidance of progressively positive fluid balances (which can lead to extracellular volume expansion and organ edema), and the possibility of overzealous fluid removal (which can lead to hypovolemic AKI).

The selection of a specific dialysis modality can have important consequences in terms of survival and quality of life. In this Review, Lameire and Van Biesen compare the epidemiology of peritoneal dialysis with that of hemodialysis and describe some of the major differences that exist in the global utilization of these two dialysis modalities. The authors describe a number of medical and nonmedical factors, including economic, educational and psychological factors that influence dialysis modality choice.

Individuals with diabetic nephropathy experience sequential abnormalities in oxygen metabolism, partly as a result of chronic hypoxia. Toshio Miyata and Charles van Ypersele de Strihou discuss molecules involved in the defense against hypoxia, especially oxygen sensors, and novel methods of inhibiting such molecules.

Chronic kidney disease (CKD) is a common condition and its prevalence is increasing. Prognosis is poor, with many patients experiencing disease progression. Recognizing the factors associated with CKD progression would enable high-risk patients to be identified and given more intensive treatment if necessary. The identification of new predictive markers might improve our understanding of the pathogenesis and progression of CKD. Here, Florian Kronenberg discusses various emerging factors and markers for which epidemiological evidence from prospective studies has shown an association with CKD progression.

Direct renin inhibition is a novel strategy for the blockade of the renin–angiotensin system. In this Review, Hollenberg discusses the evidence indicating that direct renin inhibitors might block the renin–angiotensin system in the kidney more effectively than either angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers. The author also discusses the therapeutic implications of this evidence and possible mechanisms that underlie the renal effects of direct renin inhibition.

Intradialytic hypertension is not an uncommon complication in hemodialysis patients, and seems to be associated with adverse outcomes. This complex phenomenon is not well understood, and many uncertainties exist regarding its pathophysiologic mechanisms and appropriate treatment strategies. Many of the therapeutic approaches currently used come from expert recommendations rather than from the results of randomized clinical trials. In this Review, Locatelli et al. describe the possible pathophysiologic mechanisms of intradialytic hypertension, and consider potential treatment and management strategies.

A prehypertension classification of blood pressure, encompassing a blood pressure range previously regarded to be normal that has been associated with an increased risk of hypertension mortality compared with lower blood pressure, has been established. In this Review, Pimenta and Oparil discuss the epidemiology of prehypertension, the relationship with cardiovascular morbidity and mortality, and the treatment of prehypertensive patients.

Disturbances in bone metabolism are common in patients after renal transplantation and represent important causes of morbidity and mortality. This Review discusses the etiological factors that contribute to bone metabolic disturbances in renal transplant recipients—pre-existing renal osteodystrophy, the effects of transplant-specific therapies on bone metabolism, and the effects of reduced renal function after transplantation. The clinical implications of bone disease in these patients are also considered.

Vitamin D has long been understood to be a key player in the control of bone metabolism through the regulation of calcium and phosphate homeostasis; however, growing evidence suggests this hormone may also have an important role in the progressive loss of renal function. In this Review, the authors discuss the pathogenic consequence of vitamin D deficiency on the kidney and describe the renoprotective potential of vitamin D analogues for patients with kidney disease.

According to the 'lipid nephrotoxicity hypothesis', hyperlipidemia resulting from physiological compensatory synthesis of lipoproteins in response to urinary loss of albumin can itself cause or aggravate glomerular and tubulointerstitial disease. Ruan and colleagues discuss the evidence on the mutual influence that dysregulation of lipid homeostasis and renal disease exert on each other and how such evidence confirms, qualifies and modifies the lipid nephrotoxicity hypothesis.

Proteomic research has the potential to provide disease biomarkers to clinical practice and insight into pathological mechanisms. In this Review, Welberry Smith and colleagues present an overview of the state of the art of proteomic analysis applied to the study of kidney diseases and discuss future directions of this research field and likely developments.

Studies in Africa have reported differing prevalence rates of renal disease in HIV; however, extrapolation of US statistics suggests that between 770,000 and 2.6 million people in sub-Saharan Africa could have HIV-associated nephropathy. This Review provides a global overview of HIV-related kidney disease to set the scene for a detailed analysis of this issue in Africa. The authors proffer advice on how to prevent or slow progression of renal disease and outline options for renal replacement therapy.

The two most common forms of HIV-related renal disease are HIV-associated nephropathy and a collection of immunoglobulin-related glomerulonephritides known as HIV immune complex kidney diseases. In this Review, Bruggeman and Nelson discuss the pathogenesis of these two diseases focusing on topics that remain points of controversy, such as mechanisms of infection within the kidney, modeling of disease in rodents, the contribution of host immune responses, and the source of the proliferating glomerular epithelial cell.

The presence of HIV has historically been viewed as a contraindication to transplantation because of the risks associated with immunosuppression in patients who are already immunocompromised, the lack of long-term outcomes data to justify the use of a limited supply of donor organs, and the possibility of viral transmission to surgical staff. Frassetto and colleagues examine the issues surrounding kidney transplantation in patients with HIV and describe a range of strategies that optimize outcomes in these individuals.

Highly active antiretroviral therapy (HAART) has a variety of adverse renal effects. Patients receiving HAART can develop acute kidney injury, which can progress to chronic kidney disease. HAART also contributes indirectly to kidney disease by increasing the risk of diabetes and hypertension. This Review describes the epidemiology, mechanisms and diagnosis of HAART-related kidney damage, with an emphasis on the preventive management of risk factors such as intravascular volume depletion and pharmacological interactions.

Abnormalities of immunoglobulin free light chains (FLCs) are frequently present in patients with monoclonal gammopathies and can cause kidney disease. The recent introduction of highly sensitive immunoassays that measure FLCs to levels below those present in normal individuals has provided a new tool for diagnosis and management in this setting. In this article, Hutchison and colleagues review the biology of FLC production in health and disease, and the utility of FLC immunoassays in the assessment of monoclonal gammopathies in kidney disease.

The heart and kidney can mutually influence each other's function so that dysfunction in one organ can result in dysfunction in the other. In this Review, Khaled Shamseddin and Patrick Parfrey describe the mechanisms involved in this two-way interaction, with reference to the classification of the so-called cardiorenal syndromes introduced in 2008 by Claudio Ronco and colleagues.

Kidney Disease: Improving Global Outcomes (KDIGO) is an independent organization that aims to improve care and outcomes for patients with kidney disease worldwide through the development and dissemination of clinical practice guidelines. In this Review, the current co-chairs of KDIGO discuss the structure, methodology and activities of KDIGO and describe how KDIGO is trying to meet the multiple challenges of guideline development.

The incidence and mortality of sepsis and the associated development of acute kidney injury (AKI) remain high, despite intense research into potential treatment strategies. Inducible nitric oxide synthase—which is constitutively expressed in the kidney but is not expressed in many other organs—has known importance in the pathogenesis of sepsis-induced AKI in humans. In this article, Heemskerk and colleagues discuss the selective inhibition of iNOS as a potential novel treatment for sepsis-induced AKI.

In this Review, Schurman and Scheinman detail the clinical and genetic features of syndromes with a defined genetic basis that are characterized by the concomitant presence of abnormalities of the central nervous system and kidneys. The authors focus their attention on the oculocerebrorenal syndrome of Lowe and on ciliopathies—particularly Joubert syndrome and Bardet–Biedl syndrome.