Volume 9 Issue 11, November 2013

Follow-up data from the RAVE trial have shown that rituximab is as effective as immunosuppression with cyclophosphamide followed by azathioprine in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis. Rituximab is likely to become the standard of care for many patients with ANCA disease. However, an individualized approach is needed to identify those who require more-intense or prolonged therapy.

A new study provides cogent evidence that fluid overload—measured using bioimpedance spectroscopy—promotes progression of chronic kidney disease (CKD). A prospective randomized trial is warranted to assess the effect of interventions to reduce fluid overload on disease progression in patients with CKD.

Renal biopsy is the gold standard for detection of rejection in kidney transplant recipients, but is not considered until evidence of renal dysfunction is apparent. Now, Suthanthiran and colleagues suggest that mRNA levels in urinary cells from these patients might be diagnostic and prognostic of acute cellular rejection.

New data suggest that arteriovenous fistulas compared with prosthetic grafts may not be a superior predialysis approach to vascular access for haemodialysis in patients aged ≥80 years. However, the use of catheters as the first vascular access was associated with significantly increased mortality in these patients and should be avoided.

Current guidelines recommend lowering blood pressure (BP) in patients with chronic kidney disease and hypertension. However, a new study suggests that achieving ideal systolic BP targets at the expense of low diastolic BP <70 mmHg is not advantageous for outcomes.

Two trials of low-glucose-containing peritoneal dialysis regimen in patients with diabetes mellitus show that although this strategy improved glycaemic control, it was associated with increased risk of serious adverse events and mortality. These studies suggest caution is needed when evaluating effectiveness using surrogate measures and awareness of confounding factors is important.

A recent study developed a formula predicting hard outcomes of rhabdomyolysis (dialysis and death). Based on a rigid analytical approach, an eight factor score was elaborated with acceptable prognostic value, but clinical usefulness at this time seems limited. Perhaps the most promising application is for triage.

In a meta-analysis of randomized trials, de Borst and colleagues report that vitamin D therapy reduces proteinuria and might also slow the progression of chronic kidney disease. In light of the limited options for renoprotective therapy, we evaluate whether this evidence for vitamin D treatment justifies a large, definitive trial.

Chronic kidney disease (CKD) is associated with high levels of serum phosphate, fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH). FGF-23 acts in the kidney to induce phosphaturia and inhibit the synthesis of 1,25-dihydroxyvitamin D₃. Here, the authors discuss the pathogenesis of increased FGF-23 levels in secondary hyperparathyroidism associated with CKD.

In this Review, the author discusses new insights into the pathogenesis of chronic kidney disease and describes a novel mechanism of ageing, both in the context of the fibroblast growth factor (FGF)–Klotho endocrine axis. In addition, the author proposes a new paradigm for dietary phosphate restriction in which phosphate restriction is started when serum FGF-23 level starts to rise, regardless of serum phosphate level.

Cardiovascular mortality is very high in young patients with chronic kidney disease (CKD), and it has been suggested that patients with CKD exhibit a 'premature ageing' phenotype. This Review discusses data showing that uraemic toxins can drive vascular smooth muscle cell damage and phenotypic changes that promote vascular calcification. It also describes emerging data indicating that uraemic toxins may also promote DNA damage, which drives cellular ageing.

Changes in bone quality and quantity are associated with an increased risk of fracture in patients with chronic kidney disease–mineral and bone disorder (CKD–MBD). Here, methods used to assess bone quality abnormalities across different hierarchical levels are outlined, as well as the results, such as abnormalities in structural parameters and bone material or mechanical properties, which are linked to an increased risk of fracture. Such assessment will improve our understanding of CKD–MBD and aid therapeutic development.

Patients with chronic kidney disease (CKD) have a high risk of bone fracture and low bone mineral density, which resembles osteoporosis. However, the mineral and bone disorder associated with CKD (CKD–MBD) is more complex than osteoporosis and the same treatments might not be appropriate in these patients. In this Review, Susan Ott discusses therapies for osteoporosis, and the evidence for their use in patients with CKD–MBD.

The metabolic changes that are associated with chronic kidney disease (CKD) can result in dramatic changes in bone and mineral metabolism and the development of vascular calcification. Altered levels of serum phosphate, vitamin D, calcium, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) contribute to changes in bone remodelling and the increased cardiovascular mortality observed in patients with CKD. This focus issue features five Reviews written by key opinion leaders who presented at the International Society of Nephrology's Nexus Symposium on Bone and the Kidney held in Copenhagen in September 2012. Topics covered include the role of Klotho, phosphate and FGF-23 in ageing and disturbed mineral metabolism, secondary hyperparathyroidism, mechanisms of vascular calcification in CKD, methodologies for assessing bone quality, and the management of osteodystrophy in patients with CKD.