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Bristol, United Kingdom

Shroff R.,Renal Unit
Pediatric Nephrology | Year: 2013

Elevated phosphate (P) levels are seen in advanced renal failure and, together with dysregulated calcium, parathyroid hormone and vitamin D levels, contribute to the complex of chronic kidney disease-mineral and bone disease (CKD-MBD). Converging evidence from in vitro, clinical and epidemiological studies suggest that increased P is associated with vascular calcification and mortality. When vessels are exposed to high P conditions in vitro, they develop apoptosis, convert to bone-like cells and develop extensive calcification. Clinical studies in children on dialysis show that high P is associated with increased vessel wall thickness, arterial stiffness and coronary calcification. Epidemiological studies in adult dialysis patients demonstrate a significant and independent association between raised P and mortality. Importantly, raised P is associated with cardiovascular changes even in pre-dialysis CKD, and also in subjects with normal renal function but high P. All P binders can effectively reduce serum P, and this decrease is linked to improved survival. Raised serum P triggers the release of fibroblast growth factor 23 (FGF-23), which has the beneficial effect of increasing P excretion in early CKD, but is increased several 1,000-fold in dialysis, and may be an independent cardiovascular risk factor. Both FGF-23 and its co-receptor Klotho may have direct effects on the vasculature leading to calcification. Fascinatingly, disturbances in FGF-23-Klotho and raised P have also been associated with premature aging. These data suggest that high P levels have adverse vascular effects and that maintaining the serum P levels in the normal range reduces cardiovascular risk and mortality. © 2012 IPNA.

This post hoc analysis of the recently reported Frequent Hemodialysis Network Trials suggests that frequent nocturnal treatment, unlike frequent daily treatment, may be associated with more rapid loss of residual kidney function than conventional hemodialysis. Differences in blood pressure control, among other factors, may be implicated. The study invites reflection on our current concepts of the importance of preserving residual kidney function and on the indications for frequent treatments, particularly nocturnal. © 2013 International Society of Nephrology.

Roger S.D.,Renal Unit
Expert Opinion on Biological Therapy | Year: 2010

Importance of the field: Expiration of patents covering biopharmaceuticals, has provided opportunities for pharmaceutical companies to develop, produce and market biosimilars or follow-on biologicals. However, there have been concerns over the degree of similarity of these complex drugs in addition to the hope that their introduction may lower the cost of such expensive medicinal products. Areas covered in this review: The introduction/manufacturing considerations, immunogenicity and regulatory approaches to biosimilars around the world. In addition, arguments and techniques employed by pharmaceutical companies to advance or discredit biosimilar drugs will be outlined. Issues with post-marketing surveillance programmes and their limitations are described. What the reader will gain: This evaluation outlines the controversial issues associated with introduction of biosimilar medicines across a range of pharmacological indications. Also the differences between regulatory approved medicines and biopharmaceutical products not subjected to regulatory approval ('B-NSRA') are highlighted. The review is limited by the rapid changes in regulatory approval and licencing of biosimilars. Take home message: Hopefully biosimilar medicines will allow more widespread availability of expensive biopharmaceutical products. Clinicians need to be wary of non-transparent promotion of innovator/biosimilar products. © 2010 Informa UK Ltd.

Sinico R.A.,Clinical Immunology Unit and Renal Unit | Di Toma L.,Renal Unit | Radice A.,Microbiology Institute
Autoimmunity Reviews | Year: 2013

Renal involvement is a common and often severe complication of anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitides (AAV).With the exception of Churg-Strauss syndrome (CSS), where kidney involvement is not a prominent feature, renal disease is present in about 70% of patients with Wegener's granulomatosis, now called granulomatosis with polyangiitis (GPA) and in almost 100% of patients with microscopic polyangiitis (MPA). Kidney involvement is generally characterized by a pauci-immune necrotizing and crescentic glomerulonephritis with a very rapid decline of renal function (rapidly progressive glomerulonephritis). Even though there are not qualitative differences in glomerular lesions in patients with GPA or with MPA, chronic damage is significantly higher in MPA (and/or P-ANCA positive patients) than in GPA (and/or C-ANCA positive patients). If untreated necrotizing and crescentic glomerulonephritis has an unfavorable course leading in a few weeks or months to end stage renal disease. Serum creatinine at diagnosis, sclerotic lesions and the number of normal glomeruli at kidney biopsy are the best predictors of renal outcome. Corticosteroids and cyclophosphamide (with the addition of plasma exchange in the most severe cases) are the cornerstone of induction treatment of ANCA-associated renal vasculitis, followed by azathioprine for maintenance. Rituximab is as effective as cyclophosphamide in inducing remission in AAV and probably superior to cyclophosphamide in patients with severe flare, and could be preferred in younger patients in order to preserve fertility and in patients with serious relapses. © 2012 Elsevier B.V.

Tsagalis G.,Renal Unit
Hippokratia | Year: 2011

Albeit the considerable progress that has been made both in our understanding of the pathophysiology of acute renal failure (ARF) and in its treatment (continuous renal replacement therapies), the morbidity of this complex syndrome remains unacceptably high. The current review focuses on recent developments concerning the definition of ARF, new strategies for the prevention and pharmacological treatment of specific causes of ARF, dialysis treatment in the intensive care setting and provides an update on critical care issues relevant to the clinical nephrologist.

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