Viewpoint

Earlier this year, the FDA responded to the findings of CHOIR and several other studies by issuing a Public Health Advisory about the risks associated with erythropoiesis-stimulating agents, and introducing a black box warning to the labeling of these drugs. In this Viewpoint, Ajay K Singh responds to some of the criticisms that have been leveled at CHOIR and offers some practical advice for implementing the FDA's guidance.

A group chaired by a rheumatologist recently published a consensus document inArthritis and Rheumatismthat codified definitions of renal responses and non-responses to therapy in patients with lupus nephritis. In this Viewpoint, the co-director of a renal-rheumatology lupus clinic argues that nephrologists have a key role to play in the diagnosis and treatment of lupus nephritis, and that they should not allow rheumatologists to take over the management of this condition.

For clinicians treating chronic conditions such as end-stage renal disease (ESRD), the quality of patients' lives is an important consideration. This Viewpoint highlights the ways in which health-related quality of life can be measured in ESRD (e.g. with generic instruments that facilitate comparisons with the general population and between countries), and the difficulties of such measurement. The authors offer their suggestions of how best to obtain and use this information to improve the care and outcomes of patients with ESRD.

In formulating a clear and succinct answer to the question posed by this Viewpoint, the authors highlight several important considerations. They discuss how the choice of induction agent, the presence of risk factors for relapse and the definition of remission can influence the timing of the switch to maintenance therapy and/or the duration of maintenance treatment in patients with ANCA-associated vasculitis.

Focusing largely on end-stage renal disease, this Viewpoint outlines some echocardiographic indices of left ventricular function, and examines their prognostic value in chronic kidney disease. Recommendations are provided for optimal indexing of estimates of left ventricular mass to body size in this population. The role of echocardiography as an outcome measure in interventional studies and in the longitudinal monitoring of cardiac risk are also briefly considered.

The author of this counterpoint argues that the results of recently published randomized clinical trials call into question the assumption that continuous renal replacement therapy is inherently superior to intermittent hemodialysis for patients in the intensive care unit with severe acute kidney injury. The second half of his article examines why this might be. Has intermittent hemodialysis become safer and more efficacious? Might continuous renal replacement therapy be less safe and/or efficacious than previously thought?

The first of this pair of 'pro/con' Viewpoints sets out the case for the superiority of continuous renal replacement therapy over intermittent hemodialysis in critically ill patients with acute kidney injury. Forming the basis of the author's argument is the notion that by attempting to correct in a few minutes physiological derangements that have developed over hours or days, intermittent hemodialysis is aggressive and unphysiological; by contrast, continuous renal replacement therapy corrects derangements gently and slowly, like the native kidneys.

The US National High Blood Pressure Education Program currently advocates diuretics as first-line treatment for all patients with hypertension, based mainly on the findings of ALLHAT. This Viewpoint identifies several flaws in the design of ALLHAT that call into question the validity of its conclusions. The authors argue that by encouraging use of angiotensin-converting-enzyme inhibitors and calcium channel blockers in ways that are not the standard of care, the trial likely exaggerated the benefits of diuretics in this setting.

Taking into account the danger of provoking osmotic demyelination by causing an overly rapid rise in the plasma sodium level, these authors from the University of Toronto offer their recommendations for correcting chronic hyponatremia. They highlight the importance of avoiding a substantial water diuresis, and discuss three key clinical settings where such a diuresis can occur.

Renal pathological changes seen in individuals with the zoonotic disease leptospirosis include interstitial nephritis and tubular necrosis. With a particular emphasis on the role of hemodynamics, this author from Thailand examines the pathogenesis of renal dysfunction in leptospirosis. The utility of dopamine in this setting is contrasted with its effects in renal dysfunction of other etiologies.

The Iranian model of kidney transplantation, whereby donors are paid by a government-sponsored agency, has eliminated the waiting list completely. Elsewhere, black markets for kidneys encourage exploitation of the poor and harm both donors and recipients. As the buying and selling of organs increases relentlessly despite legislation, this author argues that failure to regulate these practices could be considered unethical.

These authors present their controversial opinion that the evidence for a specific renoprotective effect of renin–angiotensin blockade, independent of blood-pressure control, is more ambiguous and the magnitude of any such effect much smaller than is often claimed. Data from several large trials of renin–angiotensin blockers and elegant renal cross-transplantation experiments in mice are proffered in support of their theory.

Could the shortage of transplantable kidneys in the developed world be reduced by allowing willing individuals to sell their organs? To answer this question, the authors examine the outcomes of patients who have received paid kidneys, and the financial compensation and postoperative care received by their donors. Adoption of commercial kidney transplantation in the Western world would have inevitable knock-on effects in developing countries, they argue.

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.

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.

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.

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.

Selective cyclo-oxygenase 2 inhibitors (coxibs) were designed to provide effective analgesia without the gastrointestinal toxicity of classical, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Concern has arisen, however, about the cardiovascular and renal safety of coxibs. In this Viewpoint, Matthias Hermann and Thomas F Lüscher examine the differences among these agents in their effects on sodium excretion, glomerular filtration rate and blood pressure, and provide their overall recommendation for use of these agents.

Although renal dysfunction can have a profound effect on the pathogenesis of cardiovascular disease, current guidelines for the management of hyperlipidemia in patients with chronic kidney disease (CKD) were formulated in the absence of data on cardiovascular and cerebrovascular outcomes in this population. Considering the individual stages of CKD, authors from the University of Würzburg, Germany, analyze data from the 4D trial and other studies, and attempt to answer the question of when hyperlipidemia should (or should not) be treated in patients with CKD.

Terry Strom and Manikkam Suthanthiran present the results of studies investigating the potential of transcriptional profiling, based on both polymerase chain reaction and DNA array technologies, to identify renal allograft rejection from allograft biopsy specimens, blood and urine sediment. They argue that in future, such analysis will function not only as a surrogate for the invasive biopsy procedure, but could also have the capacity to provide predictive, diagnostic, and prognostic information.