• Viewpoint |

    Here, four leading researchers discuss key considerations related to women's kidney health, including specific risk factors, the main challenges and barriers to care and policies and systems that could be implemented to improve the kidney health of women and their offspring.

    • Gloria E. Ashuntantang
    • , Vesna D. Garovic
    • , Ita P. Heilberg
    •  & Liz Lightstone
  • Viewpoint |

    Here, five leading researchers describe changes in the epidemiology of obesity-related kidney disease, advances in current understanding of the mechanisms involved and current approaches to the management of affected patients.

    • Niels Olsen Saraiva Câmara
    • , Kunitoshi Iseki
    • , Holly Kramer
    • , Zhi-Hong Liu
    •  & Kumar Sharma
  • Viewpoint |

    In this Viewpoint, six leading researchers reflect on progress made in their specialist field of paediatric kidney disease. They provide their insight as to the direction research will take in future years, and comment on areas in which additional research or initiatives are required to improve renal outcomes and patient care for the paediatric and neonatal population.

    • John F. Bertram
    • , Stuart L. Goldstein
    • , Lars Pape
    • , Franz Schaefer
    • , Rukshana C. Shroff
    •  & Bradley A. Warady
  • Viewpoint |

    In this Viewpoint, five members of theNature Reviews Nephrologyadvisory board reflect on the progress and frustrations of the past decade in basic and clinical nephrology research. They comment on areas where effort and money should be invested and the challenges that remain to be overcome, as well as give their predictions for progress in the next decade.

    • Jürgen Floege
    • , Robert H. Mak
    • , Bruce A. Molitoris
    • , Giuseppe Remuzzi
    •  & Pierre Ronco
  • Viewpoint |

    In many low-to-middle income countries (LMICs) access to essential medications is limited and the number of clinical trials conducted is small because of regulatory issues and a lack of infrastructure. In this article,Nature Reviews Nephrologyasks three experts their opinions on how to improve drug access and increase the numbers of clinical trials conducted in LMICs.

    • Ikechi G. Okpechi
    • , Charles R. Swanepoel
    •  & Francois Venter
  • Viewpoint |

    Lower blood concentrations of protein-bound solutes have been directly linked to better outcomes in patients on dialysis. Studies indicate that clearance of protein-bound solutes is more efficient in patients on hemodialysis than in those on peritoneal dialysis; however, paradoxically, the circulating levels of these solutes are lower in patients on peritoneal dialysis. Vanholder and colleagues consider possible explanations for this discrepancy, such as differences in intestinal generation or metabolism of these molecules.

    • Raymond Vanholder
    • , Natalie Meert
    • , Wim Van Biesen
    • , Timothy Meyer
    • , Thomas Hostetter
    • , Annemieke Dhondt
    •  & Sunny Eloot
  • Viewpoint |

    Studies have shown that rituximab, a chimeric monoclonal antibody that targets the CD20 antigen of B cells, might be a valuable alternative to current therapies for idiopathic membranous nephropathy. In this Viewpoint article, Ruggenenti and colleagues discuss the use of rituximab in idiopathic membranous nephropathy and reason that titrating rituximab therapy to CD20+cell counts might be an effective way of limiting patient exposure to rituximab without reducing the efficacy of treatment, and would also substantially reduce treatment costs.

    • Piero Ruggenenti
    • , Paolo Cravedi
    •  & Giuseppe Remuzzi
  • Viewpoint |

    The role of aldosterone in the progression of kidney dysfunction, via its actions on mineralocorticoid receptors, is increasingly recognized. The authors of this Viewpoint outline the beneficial effects that have been seen in animal and human studies of mineralocorticoid receptor blockade in various forms of kidney disease. They predict that low daily doses of the aldosterone blocker spironolactone—an inexpensive, generic medication with few and easily recognizable adverse effects—might one day become the renal equivalent of 'baby' aspirin.

    • Andrew S Bomback
    • , Abhijit V Kshirsagar
    •  & Philip J Klemmer
  • Viewpoint |

    Here, Cohen and Kimmel attempt to counter the arguments presented by Lynda Szczech in the preceding Viewpoint. They point out that HIV-associated kidney disease exists in various forms that have different treatment requirements and that renal biopsy is necessary to establish the exact diagnosis. They argue, furthermore, that the efficacy and safety of highly active antiretroviral therapy against HIV-associated nephropathy is questionable and that such treatment should not, therefore, be initiated empirically.

    • Scott D Cohen
    •  & Paul L Kimmel
  • Viewpoint |

    This Viewpoint attempts to counter the arguments presented by Cravedi et al. in this issue of Nature Clinical Practice Nephrology. Although β-cell islet transplantation is not yet a widely viable treatment for type 1 diabetes, AM James Shapiro argues that the procedure's shortcomings are not insurmountable and that now is not the time for a moratorium on clinical research. Enhancing the mass of the initial islet engraftment, which would alleviate many of the present challenges, could be achieved in ongoing trials, and remarkable progress with xenotransplantation and human embryonic stem cells foreshadows the possibility of a renewable islet cell source.

    • AM James Shapiro
  • Viewpoint |

    Should renal biopsy be performed in all patients with both HIV infection and kidney disease? In this Viewpoint, Dr Szczech argues that, given its efficacy against conditions like HIV-associated nephropathy, antiretroviral therapy should be implemented before biopsy is considered. Only when suppression of viral replication fails to improve renal function does the case for biopsy become more compelling. In any event, much as with HIV-negative patients with renal disease, empiric therapy should be implemented before renal biopsy is undertaken.

    • Lynda A Szczech
  • Viewpoint |

    The enthusiasm for pancreatic β-cell islet transplantation that followed the introduction of the 'Edmonton protocol' in 2000 has been tempered by evidence that the immunosuppressants used in the protocol might be nephrotoxic and that the resultant insulin independence is only short-term in most patients. Cravedi and colleagues analyze the risks and benefits of islet transplantation and argue that it should not be regarded as a general alternative to insulin replacement therapy for patients with type 1 diabetes mellitus.

    • Paolo Cravedi
    • , Roslyn B Mannon
    • , Piero Ruggenenti
    • , Andrea Remuzzi
    •  & Giuseppe Remuzzi
  • Viewpoint |

    The development of a wearable device that can replace conventional dialysis in patients needing chronic renal replacement therapy is not as far-fetched as it once was. Ronco et al. describe technological achievements, propose future research directions and discuss the clinical, technical and socioeconomic reasons for continuing the push to realize the wearable artificial kidney.

    • Claudio Ronco
    • , Andrew Davenport
    •  & Victor Gura
  • Viewpoint |

    Various strategies have been considered in attempts to improve the outcomes of dialysis patients. Such strategies include increasing dialysis dose, using alternative depuration methods, changing dialysis schedules and focusing on preventing or treating specific co-morbidities and complications. In this Viewpoint, Andreas Pierratos discusses the first three strategies, and concludes that he believes that a paradigm shift, a disruptive change-in the form of daily home nocturnal hemodialysis-is needed to improve dialysis outcomes.

    • Andreas Pierratos
  • Viewpoint |

    Lymphocyte depletion has recently been adopted to allow immunosuppression minimization or even to achieve donor-specific tolerance in transplant recipients. The long-term aim of such therapy is to minimize toxic effects associated with standard immunosuppression, but this beneficial effect is offset by the potential toxicity of the global depletion of lymphocytes and, in some cases, monocytes and neutrophils. This Viewpoint summarizes current data on depletion strategies in kidney transplantation, typically in the setting of induction treatment.

    • Paolo Cravedi
    • , Roslyn B Mannon
    •  & Giuseppe Remuzzi
  • Viewpoint |

    Inhibitors of vascular endothelial growth factor, such as bevacizumab, are a promising approach to the treatment of tumors and other angiogenesis-dependent conditions. However, it is becoming increasingly obvious that these drugs can have serious adverse effects including proteinuria, hypertension and thrombotic microangiopathy. This Viewpoint evaluates current evidence to argue that these adverse effects are probably elicited by inhibition of nitric oxide production in the renal vasculature.

    • Jecko Thachil
  • Viewpoint |

    Multifactorial approaches to the treatment of type 2 diabetes mellitus have proven more effective than any individual intervention alone in reducing the risk of cardiovascular complications. As the spread of diabetes and obesity accelerates worldwide, unhindered by lifestyle modification approaches, the authors of this Viewpoint propose an aggressive multifactorial strategy for treating patients who have one or more risk factors for the metabolic syndrome in an effort to prevent or delay the onset of diabetes.

    • Robert W Schrier
    •  & Yolanda E Bogaert
  • Viewpoint |

    Although low-molecular-weight heparins (LMWHs) have largely replaced unfractionated heparin for the treatment of deep vein thrombosis and pulmonary embolism in the general population, sufficiently powered clinical studies on the use of LMWHs in patients with renal impairment are lacking. In this Viewpoint article, Gallieni and colleagues discuss reasons why LMWHs should be used with caution, at present, in patients with chronic kidney disease.

    • Maurizio Gallieni
    • , Mario Cozzolino
    • , Chiara Ronga
    •  & Diego Brancaccio
  • Viewpoint |

    According to the Kidney Disease Outcomes Quality Initiative guidelines, estimated glomerular filtration rate can be used to diagnose chronic kidney disease. The authors of this Viewpoint argue, however, that reliance on estimated glomerular filtration rates alone encourages an erroneous disregard of age, gender and other evidence of kidney disease, such as proteinuria. Consequently, mandatory reporting of estimated glomerular filtration rate leads to misdiagnosis of chronic kidney disease and to the unhelpful referral of healthy individuals to nephrologists.

    • Richard J Glassock
    •  & Christopher G Winearls
  • Viewpoint |

    A relationship between disturbed lipid metabolism and kidney disease was first postulated in 1858. Over the years, many animal studies have indicated that lipids have a pathophysiologic role in renal disease. The authors of this Viewpoint describe the possible mechanisms through which lipids might promote the progression of glomerular and tubulointerstitial diseases.

    • Elisabeth F Gröne
    •  & Hermann-Josef Gröne
  • Viewpoint |

    This, the second of two opposing Viewpoints, presents the case for the use of cinacalcet for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease who are not receiving dialysis. The authors assert that cinacalcet effectively reduces serum parathyroid hormone level in this setting, and that any adverse effects of the drug on calcium or phosphorus levels can be managed by monitoring and treating patients accordingly.

    • Angel LM de Francisco
    • , Celestino Piñera
    •  & Rosa Palomar
  • Viewpoint |

    In the first of two opposing Viewpoints, Daniel W Coyne questions the use of cinacalcet to treat secondary hyperparathyroidism in non-dialysis-dependent patients with chronic kidney disease. He highlights the absence of FDA approval and the lack of published data for cinacalcet in this setting. Cinacalcet does not, he argues, address a universal pathophysiologic feature of secondary hyperparathyroidism; in addition, it has considerable adverse effects.

    • Daniel W Coyne
  • Viewpoint |

    The authors of this Viewpoint argue that the currently used definitions of cardiorenal syndrome fail to take into account the complex bidirectional nature of the relationship between the heart and kidneys. They propose a new classification of the condition, comprising five subtypes that are distinguished on the basis of the primary and secondary pathology and its chronology. Examples of each subtype are provided.

    • Claudio Ronco
    • , Andrew A House
    •  & Mikko Haapio
  • Viewpoint |

    In the late 1990s, a series of papers described the isolation and propagation of calcified, nanometer-sized structures from calf serum and diseased tissues. These findings prompted researchers at the Mayo Clinic, Rochester, MN to investigate the possibility that transmissible biologic nanoparticles could be responsible for pathologic calcification in the kidneys and blood vessels. Here, a member of the Mayo group summarizes the research to date in this exciting field.

    • John C Lieske
  • Viewpoint |

    Reports from Japan indicate that renal artery embolization holds promise for relieving the 'mass effect' symptoms of autosomal dominant polycystic kidney disease. Authors from the University of Maryland School of Medicine compare the safety and efficacy of this procedure with that of the techniques more widely used to relieve the symptoms of autosomal dominant polycystic kidney disease, including nephrectomy, cyst marsupialization and cyst decortication.

    • Matthew S Bremmer
    •  & Stephen C Jacobs
  • Viewpoint |

    It is widely asserted that C-reactive protein (CRP) is a strong independent predictor of atherothrombotic events, and furthermore that CRP is also a pathogenic mediator of atherosclerosis. Here, the author, who first reported the predictive association of CRP with atherothrombotic events, attempts to correct these misapprehensions. He highlights the lack of a convincing association between CRP values and atherosclerosis burden, the fact that the association between baseline CRP values and coronary heart disease is substantially weaker than originally claimed, the nonspecificity of the CRP response and the flaws of cell culture studies with recombinant CRP.

    • Mark B Pepys
  • Viewpoint |

    'Middle molecules' (those in the molecular weight range of 500–60,000 Da, such as β2-microglobulin), are not easily removed by dialysis and are believed to mediate some of the effects of the uremic syndrome. The authors of this Viewpoint argue that Kt/Vureais flawed as a sole indicator of dialysis adequacy, and that we need new indices to quantify removal of these middle molecules in patients on dialysis.

    • Raymond Vanholder
    • , Sunny Eloot
    •  & Wim Van Biesen
  • Viewpoint |

    Despite advances in immunosuppressive regimens, expansion of donor acceptability criteria and introduction of paired kidney donation programs, the disparity between the number of patients awaiting a kidney transplant and the number of available organs is widening. The authors of this Viewpoint argue that increasing the rate of living kidney donation is the most promising means of enlarging the donor pool, and that laparoscopic nephrectomy has a crucial role in this endeavor.

    • Soroush Rais-Bahrami
    •  & Louis R Kavoussi
  • Viewpoint |

    Symptomatic stenoses of arteriovenous hemodialysis fistulas can be treated with surgery or endovascular dilatation. Here, an interventional radiologist argues that the minimal invasiveness and better venous preservation associated with endovascular treatment more than offset the disadvantages of poor primary patency rates and high cost, regardless of whether the fistula is located in the upper or lower forearm. Specific contraindications to each approach are also highlighted.

    • Luc Turmel-Rodrigues
  • Viewpoint |

    The authors of this Viewpoint reframe the current controversy regarding the use of calcium-based versus non-calcium-based phosphate binders in patients on dialysis. They argue that clinicians should not be asking whether the safety and efficacy data for non-calcium-based phosphate binders have reached the level of scientific certainty that supports adoption of these agents as the new standard of care. Rather, clinicians should be asking whether the evidence is sufficient to abandon the potentially harmful current standard of care.

    • David M Spiegel
    •  & Geoffrey A Block
  • Viewpoint |

    The authors proffer their response to the question previously posed by Joanne Bargman inNature Clinical Practice Nephrology: “Why are rheumatologists treating lupus nephritis?” They argue that rheumatologists are often the first point of call for patients presenting with systemic lupus erythematosus, and that they are also more adept than nephrologists at assessing certain extrarenal manifestations of the disease. Thus, the rheumatologist is ideally placed to design and monitor treatment, with the aid of a nephrologist.

    • Cees GM Kallenberg
    •  & Marc Bijl
  • Viewpoint |

    Screening for chronic kidney disease in patients with diabetes should encompass not only testing for albuminuria, but also the subsequent diagnostic procedures and interventions. Otherwise, what is the purpose of testing? The authors of this Viewpoint highlight the inadequacies of current screening practices, and argue that detection of increased urinary albumin excretion in a patient with diabetes should be a call to action.

    • Merlin C Thomas
    • , GianCarlo Viberti
    •  & Per-Henrik Groop
  • Viewpoint |

    Since the publication of the CHOIR and CREATE study results, tremendous attention has focused on the cardiovascular effects of anemia correction in patients with chronic kidney disease. Less publicized has been the finding of a potentially higher risk of progression to end-stage renal disease among patients assigned to a higher hemoglobin target. Ajay K Singh examines whether the sum of evidence indicates a harmful or a beneficial effect of anemia correction on the progression of kidney disease.

    • Ajay K Singh
  • Viewpoint |

    In the second of two opposing Viewpoints, these authors from the Greenslopes and Princess Alexandra Hospital Hypertension Units in Brisbane, Australia, describe why, who, and how they screen for primary aldosteronism. They argue that diagnosing (using a stepwise selective approach) and curing or specifically treating aldosterone excess is good for the patient and inexpensive compared with potentially lifelong and less-effective nonspecific antihypertensive therapy.

    • Richard D Gordon
    •  & Michael Stowasser
  • Viewpoint |

    This, the first of two opposing Viewpoints, sets out the arguments against screening for primary aldosteronism. The author, from the Western General Hospital in Edinburgh, UK, asserts that the majority of individuals with a high aldosterone:renin ratio have a normal plasma aldosterone level. Physicians should, therefore, focus on optimizing the excretion of salt and water in hypertensive patients rather than on expensive tests to detect an aldosterone-secreting adenoma.

    • Paul Padfield
  • Viewpoint |

    This Viewpoint puts forward the intriguing hypothesis that vitamin K is a modifiable risk factor for vascular calcification in patients on dialysis. Reports linking vitamin K with regulation of vascular calcification via the actions of matrix GLA protein are set in the context of the authors' own data on the incidence of subclinical vitamin K deficiency and the use of the vitamin K antagonist warfarin in the dialysis setting.

    • Rachel M Holden
    •  & Sarah L Booth
  • Viewpoint |

    Since the first successful transplantations were performed around 50 years ago, the lack of improvement in long-term graft survival and the risks associated with immunosuppressive therapy have made the ability to induce tolerance a burning desire among transplantation immunobiologists. These authors outline the considerable challenges that stand in the way of this goal, and proffer their opinion on which strategies are most likely to succeed.

    • M Javeed Ansari
    •  & Mohamed H Sayegh
  • 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.

    • Ajay K Singh
  • Viewpoint |

    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.

    • Joanne M Bargman
  • Viewpoint |

    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.

    • Shunichi Fukuhara
    • , Shin Yamazaki
    • , Yasuaki Hayashino
    •  & Joseph Green
  • Viewpoint |

    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.

    • Oliver Flossmann
    •  & Kirsten de Groot
  • Viewpoint |

    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.

    • Carmine Zoccali
  • Viewpoint |

    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?

    • Jonathan Himmelfarb
  • Viewpoint |

    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.

    • Claudio Ronco
  • Viewpoint |

    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.

    • Lee A Hebert
    • , Brad H Rovin
    •  & Christopher J Hebert
  • Viewpoint |

    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.

    • Mitchell L Halperin
    •  & Kamel S Kamel
  • Viewpoint |

    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.

    • Visith Sitprija
  • Viewpoint |

    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.

    • Abdallah S Daar
  • Viewpoint |

    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.

    • Anil K Bidani
    •  & Karen A Griffin
  • Viewpoint |

    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.

    • Vivekanand Jha
    •  & Kirpal S Chugh