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.

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.

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.

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.

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.

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.

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.

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.

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.

'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/V_ureais 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.