Reviews & Analysis

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.

By reducing the plasma concentration of nephrotoxic myeloma paraproteins, plasmapheresis could promote recovery of renal function and lessen the need for chronic dialysis in patients with myeloma cast nephropathy. Weighing up the findings and limitations of the three randomized controlled trials of plasmapheresis conducted to date in myeloma cast nephropathy, the author considers whether there is, or might be in future, a place for it in this setting.

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.

Progressive renal fibrosis is characteristic of all the diseases that cause renal failure. Although this process is invariably associated with leukocyte infiltration, the extent to which it is controlled by these infiltrating cells is unclear. Corralling data on the roles of macrophages in progressive renal scarring, Andrew J Rees considers whether leukocyte infiltration could be successfully harnessed as a therapeutic target in this setting.

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.

Even advanced sclerotic glomeruli show ongoing cell turnover, indicating that there is potential for modulation of the progressive renal scarring seen in chronic kidney disease. Agnes Fogo examines the mechanisms of glomerulosclerosis, with a particular focus on the pivotal role of angiotensin, and considers the potential reversibility of the processes involved.

In the third article of our series on secondary hyperparathyroidism in renal disease, Joachim Ix and colleagues comment on the recommendations put forth by Matthieu Monge et al. on page 326. Ix et al. contend that the changes to current practice proposed by Monge and colleagues are supported by insufficient evidence and should be revisited only when more data from high-quality trials become available.

This Review focuses on the role of drugs such as cinacalcet in the treatment of uremic secondary hyperparathyroidism. The authors present evidence to support their assertion that cinacalcet plus higher doses of calcium-based oral phosphate binders is a safe and efficacious alternative to currently recommended regimens. Other indications for calcimimetic drugs, such as predialysis secondary hyperparathyroidism and hypercalcemic hyperparathyroidism following kidney transplantation, are also discussed.

Since the latest K/DOQI guidelines were formulated, new data on drugs such as lanthanum carbonate and calcimimetics have become available. In light of this new information, Matthieu Monge and colleagues believe that current practice can be updated. In this Review, the authors outline their recommendations regarding drug selection, dosing regimens, and monitoring of hyperparathyroidism in dialysis patients.

Jörg Radermacher argues that although renal resistive index is not a perfect test for renovascular disease or ischemic nephropathy, it can provide useful diagnostic information in both of these settings. The author examines the utility of renal resistive index measurements in the diagnosis of renal artery stenosis, ischemic nephropathy and hypertensive nephrosclerosis.

Existing treatments for amyloidosis aim to perturb production of pathogenic fibrils by limiting the supply of precursor proteins. Recent insights into processes involved in fibrillogenesis have opened new therapeutic avenues. In this short Review, the authors provide an update on the development of drugs to stabilize precursor proteins, promote clearance of amyloid or enhance regression of fibrils.

This is a practical guide to viruses that perturb renal function, with an emphasis on those that affect glomeruli. Touching on the mechanisms that underlie viral nephropathy before focusing on clinical presentation, diagnosis and treatment, this article covers HIV, hepatitis B and C, parvovirus B19, hantavirus and the coronavirus that causes severe acute respiratory syndrome.