C4d staining of renal allografts is regarded as an in situ marker of active humoral rejection. Few data are available about the incidence of C4d deposition in protocol biopsies compared to indication biopsies. To evaluate whether center-specific factors influence the incidence of C4d detection, we performed a multicenter study. From three European centers, 551 protocol and 377 indication biopsies were reclassified according to the updated Banff criteria and stained for C4d. C4d results were recorded as diffuse or focal positive and statistically correlated to clinical parameters, morphology and graft survival. In the protocol biopsies, a diffuse C4d stain was found in 2.0%, and a focal stain in 2.4%. In indication biopsies, 12.2% were diffusely and 8.5% focally C4d positive (protocol:indication p < 0.0001). The incidence of C4d deposition varied significantly between centers, attributable to variable numbers of presensitized patients with more C4d positive indication and protocol biopsies. Diffuse and focal C4d stain correlated with morphology of humoral rejection in protocol as well as in indication biopsies. Protocol biopsies show a significantly lower incidence of C4d deposition than indication biopsies. Subclinical C4d detection in protocol biopsies had no significant impact on allograft survival in our series.

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In general, proposals for continuing or stopping metformin therapy in CKD involve a threshold (whether based on serum creatinine or estimated glomerular filtration rate) rather than the dose adjustment as a function of renal status (in stable patients) performed for other drugs excreted by the kidney.

Renal function impairment goes along with a disturbed calcium, phosphate, and vitamin D metabolism, resulting in secondary hyperparathyroidism (sHPT). These mineral metabolism disturbances are associated with soft tissue calcifications, particularly arteries, cardiac valves, and myocardium, ultimately associated with increased risk of mortality in patients with chronic kidney disease (CKD). sHPT may lead to cardiovascular calcifications by other mechanisms including an impaired effect of parathyroid hormone (PTH), and a decreased calcium-sensing receptor (CaR) expression on cardiovascular structures. PTH may play a direct role on vascular calcifications through activation of a receptor, the type-1 PTH/PTHrP receptor, normally attributed to PTH-related peptide (PTHrP). The CaR in vascular cells may also play a role on vascular mineralization as suggested by its extremely reduced expression in atherosclerotic calcified human arteries. Calcimimetic compounds increasing the CaR sensitivity to extracellular calcium efficiently reduce serum PTH, calcium, and phosphate in dialysis patients with sHPT. They upregulate the CaR in vascular cells and attenuate vascular mineralization in uremic states. In this article, the pathophysiological mechanisms associated with cardiovascular calcifications in case of sHPT, the impact of medical and surgical correction of sHPT, the biology of the CaR in vascular structures and its function in CKD state, and finally the role played by the CaR and its modulation by the calcimimetics on uremic-related cardiovascular calcifications are reviewed.

Bisphosphonates are inhibitors of bone resorption that are widely used to treat osteoporosis. Price and colleagues demonstrate that ibandronate suppressed the development of uremia-related vascular calcification in rats. These findings extend the link between bone remodeling and vascular calcification to the context of chronic renal failure, opening perspectives toward novel therapeutic strategies.

Deflazacort and prednisone were given to 26 patients with rheumatoid arthritis, polymyalgia rheumatica, or other chronic inflammatory diseases, in a double-blind study. Deflazacort rapidly and effectively suppressed disease activity in a manner supporting its assumed therapeutic potency of 83% that of prednisone. Prednisone induced a rapid increase in the level of daily calcium excretion that was not evident with deflazacort. Cortisol secretion was acutely inhibited by prednisone, but not by deflazacort. Neither corticosteroid had a significant effect on glucose metabolism, at the doses studied. Treatment with deflazacort may be an effective alternative to prednisone treatment, with fewer adverse effects on levels of calcium and cortisol, in patients with

Objective-Chronic renal failure (CRF) is associated with a 10-to 20-fold increase in cardiovascular risk. Vascular calcification is a prominent feature of cardiovascular disease in patients with end-stage renal failure and contributes to the excess mortality in this population. In this study, we explored in vivo X-ray microtomography (micro-CT) as a tool to detect and follow-up vascular calcifications in the aorta of living rats with adenine-induced CRF. Methods and Results-With in vivo micro-CT, calcification of the aorta in uremic rats was clearly discernible on transversal virtual cross-sections. Micro-CT findings correlated well with tissue calcium content and histology.Repetitive scans in animals with light, moderate, and severe vascular calcification showed good reproducibility with minimal interference of motion artifacts. Moreover, both calcified volume and area could be quantified with this method. Key Words: ectopic calcification Ⅲ imaging Ⅲ micro-CT Ⅲ renal failure Ⅲ kidney C hronic renal failure (CRF) is associated with a 10-to 20-fold increase in cardiovascular risk, which is responsible for Ϸ50% of the mortality in hemodialysis patients. 1 Goodman et al demonstrated that vessel calcification is already present in young hemodialysis patients and shows rapid progression. 2 In addition to increased calcification of atherosclerotic plaques, patients on dialysis also show characteristic calcifications of the vascular media, 3 which were recently shown to contribute significantly to the excess cardiovascular mortality observed in uremic patients. 4 Epidemiological studies identified elevated serum phosphate levels, increased calcium phosphate product and secondary hyperparathyroidism as risk factors for mortality in the hemodialysis population. 5,6 The causative roles of phosphate and calcium in the calcification process were elegantly demonstrated by in vitro studies showing that blockage of the Na-phosphate co-transporter in cultured vascular smooth muscle cells inhibited the calcification process induced by either elevated phosphate 7 or calcium levels. 8 Katsumata et al recently described adenine-induced CRF as a suitable animal model for uremia-related vascular calcification. 9 The availability of such a model allows for studies investigating how pharmacological agents, such as the recently developed alternative therapies to control hyperphosphatemia and secondary hyperparathyroidism, influence the CRF-related vascular calcification process and the mediators involved in it. Conclusions-InIn the present study, we evaluated whether vascular calcifications in a rat model of CRF can be visualized by in vivo high-resolution X-ray microtomography (micro-CT). This technique has recently been introduced as a promising noninvasive imaging technique in living rats and mice. Micro-CT proved to be most suitable for the visualization of bones and other calcified tissues. 10 Additionally, recent studies showed that noninvasive soft tissue imaging of the chest area was possible in living animals despite cardiac an...

Pesticides play an important role in the improvement of agricultural production, but their use may result in adverse effects on the environment, consumers, and farmers’ health. As there are limited data focusing on the factors influencing safety behavior toward pesticide use in Morocco, we conducted a cross-sectional survey in 15 rural communities of Morocco’s Fes Meknes region to assess the attitudes, knowledge, and practices regarding pesticide use. A structured questionnaire was completed, containing the data of the interviewed farmers, their behavior towards safety measures, the type of active ingredient used, as well as the perception of risks to their own health following exposure to pesticides by the existence of chronic, self-perceived symptoms. Non-probability (empirical) sampling with the quota method was carried out, which consists of constructing the sample. Results showed that most respondents have not been trained in the application of pesticides, with almost half of the farmers using a category of pesticides which are classified by the International Agency for Research on Cancer as probable human carcinogenic (i.e., Glyphosate, Malathion). In terms of pesticide storage, 40% of farmers said that they did not store pesticides in a separate room after purchasing or using them. The empty containers were buried or burnt by half of the responders, while the remainder were thrown at the edge of fields or in public dumps. Although the participants were aware of the negative effects on their own health and on the environment caused by the application of pesticides in use, the protection measures by individual equipment were insufficient. A canonical analysis indicates that these behaviors were influenced by the farming experience, the benefit of the agricultural council services, the follow-up of training, and the education level. These variables are important factors in explaining and understanding the dangers to both the environment and health caused by pesticides. The most recorded likely consequences of pesticide exposure were visual impairment (46%), followed by dizziness (44.3%), headache (39.4%), and excessive sweating (34.4%), and 30.2% of participants identified consequent respiratory problems. Extension services targeted at safety and protection measures should be developed and accompanied by educational programs to put farmers’ perceptions into practice and encourage them to adopt healthy and environmentally friendly behaviors.