Lack of evidence does not justify neglect. how can we address unmet medical needs in calciphylaxis

Calcific uraemic arteriolopathy (CUA), or calciphylaxis, is a rare disease predominantly occurring in comorbidity with dialysis. Due to the very low frequency of CUA, prospective studies on its management are lacking and even anecdotal reports on treatment remain scarce. Therefore, calciphylaxis is still a challenging disease with dismal prognosis urgently requiring adequate strategies for diagnosis and treatment.In an attempt to fill some of the current gaps in evidence on various, highly debated and controversial aspects of dialysis-associated calciphylaxis, 13 international experts joined the 1st Consensus Conference on CUA, held in Leuven, Belgium on 21 September 2015. The conference was supported by the European Calciphylaxis Network (EuCalNet), which is a task force of the ERA-EDTA scientific working group on Chronic Kidney Disease-Mineral and Bone Disorders (CKD-MBD). After an intense discussion, a 9-point Likert scale questionnaire regarding 20 items on calciphylaxis was anonymously answered by each participant. These 20 items addressed unsolved issues in terms of diagnosis and management of calciphylaxis. On the one hand, the analysis of the expert opinions identified areas of general consensus, which might be a valuable aid for physicians treating such a disease with less experience in the field. On the other hand, some topics such as the pertinence of skin biopsy and administration of certain treatments revealed divergent opinions. The aim of the present summary report is to provide some guidance for clinicians who face patients with calciphylaxis in the current setting of absence of evidence-based medicin

Bone biopsy practice patterns across Europe: the European renal osteodystrophy initiative - a position paper

Renal osteodystrophy (ROD) is a heterogeneous group of metabolic bone diseases complicating progressive chronic kidney disease (CKD). Bone biomarkers and bone imaging techniques may help to assess bone health and predict fractures in CKD but do have important inherent limitations. By informing on bone turnover and mineralization, a bone biopsy may help to guide prevention and treatment of ROD and its consequences. According to a recent survey conducted among European nephrologists, bone biopsies are performed rather exceptionally, both for clinical and research purposes. Obviously, clinical research in the field of ROD is threatened by vanishing clinical and pathological expertise, small patient cohorts and scientific isolation. In March 2016, the European Renal Osteodystrophy (EU-ROD) initiative was created under the umbrella of the ERA-EDTA CKD-mineral and bone disorder (MBD) Working Group to revitalize bone biopsy as a clinically useful tool in the diagnostic workup of CKD-MBD and to foster research on the epidemiology, implications and reversibility of ROD. As such, the EU-ROD initiative aims to increase the understanding of ROD and ultimately to improve outcomes in CKD patients

Circulating markers of bone turnover

Renal osteodystrophy is a feature of chronic kidney disease (CKD), with increasing prevalence as CKD progresses. This bone disease is responsible for major morbidity, including fractures, and a deterioration in the quality of life and its sequelae. Circulating biomarkers of renal osteodystrophy typically indicate bone turnover, but not other features of bone, like bone volume, mineralization, quality or strength. Bone turnover can be considered to be primarily a reflection of bone cell activity, in particular that of osteoblasts and osteoclasts. Since current treatments for bone disease usually target cellular activity, biomarkers are considered to be able to contribute to the decision-making for treatment and its follow-up. In CKD, one has to consider the impact of a diminished clearance of biomarkers or their altered metabolism, both potentially limiting its clinical use. Here, several aspects of the most frequently used biomarkers of bone turnover are reviewed, with an emphasis on the specific situation represented by CKD. This review is based on the overview lecture at the symposium held in Amsterdam, September 23, 2016: "The Bone In CKD", organized by the CKD-MBD working group of ERA-EDTA.status: publishe

National Kidney Foundation consensus conference on cardiovascular and kidney diseases and diabetes risk: an integrated therapeutic approach to reduce events.

Cardiovascular disease (CVD) is the most common cause of death in industrialized nations. Type 2 diabetes is a CVD risk factor that confers risk similar to a previous myocardial infarction in an individual who does not have diabetes. In addition, the most common cause of chronic kidney disease (CKD) is diabetes. Together, diabetes and hypertension account for more than two-thirds of CVD risk, and other risk factors such as dyslipidemia contribute to the remainder of CVD risk. CKD, particularly with presence of significant albuminuria, should be considered an additional cardiovascular risk factor. There is no consensus on how to assess and stratify risk for patients with kidney disease across subspecialties that commonly treat such patients. This paper summarizes the results of a consensus conference utilizing a patient case to discuss the integrated management of hypertension, kidney disease, dyslipidemia, diabetes, and heart failure across disciplines

Fisheries Act Amendment Act, 1977, No. 27

Recent reports of several bone-derived substances, some of which have hormonal properties, have shed new light on the bone-cardiovascular axis. Deranged concentrations of humoral factors are not only epidemiologically connected to cardiovascular morbidity and mortality, but can also be causally implicated, especially in chronic kidney disease. FGF23 rises exponentially with advancing chronic kidney disease, seems to reach maladaptive concentrations, and then induces left ventricular hypertrophy, and is possibly implicated in the process of vessel calcification. Sclerostin and DKK1, both secreted mainly by osteocytes, are important Wnt inhibitors and as such can interfere with systems for biological signalling that operate in the vessel wall. Osteocalcin, produced by osteoblasts or released from mineralised bone, interferes with insulin concentrations and sensitivity, and its metabolism is disturbed in kidney disease. These bone-derived humoral factors might place the bone at the centre of cardiovascular disease associated with chronic kidney disease. Most importantly, factors that dictate the regulation of these substances in bone and subsequent secretion into the circulation have not been researched, and could provide entirely new avenues for therapeutic intervention