The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

Osteopenia is frequently found among calcium stone forming (CSF) patients with hypercalciuria. We investigated the effect of a 2-year therapeutic course of etidronate, a bone-sparing agent, in 7 young male CSF patients. The treatment consisted of a cyclic intermittent administration of phosphate followed by sodium etidronate and calcium supplementation every 74 days. Bone mineral density (BMD) measured at 12-month intervals and bone biopsies performed at baseline and after 2 years were the primary efficacy parameters. Mean lumbar spine BMD increased significantly after the 1st year by 2.6 ± 1.0% (mean ± SE, p < 0.05) and nonsignificantly after the 2nd year by 5.6 ± 2.6%. Nonsignificant changes were observed for femoral neck mean BMD after either the 1st or the 2nd year (decrease of 2.0 ± 1.0% and 2.0 ± 3.0%, respectively). Mean histomorphometric parameters showed that bone volume, osteoid volume, and eroded surfaces did not differ from baseline (13.9 ± 2.2 vs. 12.2 ± 1.1%, 1.2 ± 0.7 vs. 2.6 ± 0.7%, and 20.7 ± 6.2 vs. 13.7 ± 1.3%, respectively). Osteoid surface was significantly lower than baseline values (9.5 ± 5.2 vs. 18.8 ± 5.3%, p < 0.05). These data suggest that etidronate given to young male CSF patients presenting with hypercalciuria and osteopenia led to a significant amelioration of BMD, evident only in the lumbar spine after 1 year of treatment. There was no histological evidence of long-term improvement in bone remodeling.

It has been suggested that phosphate binders may reduce the inflammatory state of hemodialysis (HD) patients. However, it is not clear whether it has any effect on oxidative stress. The objective of this study was to evaluate the effect of sevelamer hydrochloride (SH) and calcium acetate (CA) on oxidative stress and inflammation markers in HD patients. Hemodialysis patients were randomly assigned to therapy with SH (n=17) or CA (n=14) for 1 year. Before the initiation of therapy (baseline) and at 12 months, we measured in vitro reactive oxygen species (ROS) production by stimulated and unstimulated polymorphonuclear neutrophils and serum levels of tumor necrosis factor alpha, interleukin-10, C-reactive protein, and albumin. There was a significant reduction of spontaneous ROS production in both groups after 12 months of therapy. There was a significant decrease of Staphylococcus aureus stimulated ROS production in the SH group. There was a significant increase in albumin serum levels only in the SH group. In the SH group, there was also a decrease in the serum levels of tumor necrosis factor alpha and C-reactive protein. Our results suggest that compared with CA treatment, SH may lead to a reduction in oxidative stress and inflammation. Therefore, it is possible that phosphate binders exert pleiotropic effects on oxidative stress and inflammation, which could contribute toward decreasing endothelial injury in patients in HD.

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images in clinical medicineT h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 360;5 nejm.org january 29, 2009 507 S evere pain developed in the left hand of a 46-year-old woman after open heart surgery was performed to repair an atrial septal defect. It was initially thought that this pain was due to a thrombosis associated with a pressure-monitoring device in her left radial artery. Physical examination showed erythematous lesions, cyanosis, and ischemia of her left hand (Panel A). Radiographic findings revealed radiopaque particles (Panel B, black and white arrows) that were consistent with the presence of mercury in the soft tissues of her hand. The particles most likely came from the manometer used with the arterial line (a common commercial arterial-line system used in Brazil). Particles of mercury could also be seen under the skin on her thumb and fingers (Panel A, single arrows). High levels of mercury were found in her blood (192.9 μg per liter; normal value, ≤9.9) and urine (2067 μg per gram of creatinine; normal value, ≤5), but there was no evidence of associated organ damage. The patient was treated with nitroglycerin patches (Panel A, double arrows), codeine, acetaminophen, and penicillamine. On followup at 3 months, the atrial septal defect had been successfully repaired and the painful symptoms in her left hand had resolved, but part of her fifth finger had been amputated because of ischemic necrosis (Panel C). The patient was lost to subsequent follow-up.

Artigos originaisResumo OBJETIVO: avaliar os efeitos da administração crônica de três diferentes doses de Ritonavir nos fígados e rins de ratas prenhes e seus conceptos do ponto de vista morfológico. MÉTODOS: Quarenta ratas albinas EPM-1 Wistar, prenhes, foram aleatoriamente divididas em quatro grupos: Contr (controle do veículo) e três grupos experimentais, Exp20, Exp60 e Exp180, que receberam, respectivamente, 20, 60 e 180 mg/kg por dia de Ritonavir por via oral. A droga e o veículo (propilenoglicol) foram administrados por gavagem, desde o primeiro até o 20º dia da prenhez. No último dia do experimento, todos os animais foram anestesiados e sacrificados. Em seguida, fragmentos dos fígados e rins maternos e fetais foram coletados e preparados para análise em microscopia de luz. RESULTADOS: não observamos nenhuma alteração morfológica nas vísceras estudadas nos Grupos Contr e Exp20. No Grupo Exp60, encontramos, no fígado materno, hepatócitos com sinais de atrofia e de apoptose (eosinofilia citoplasmática e núcleos picnóticos) e vasodilatação marcante dos capilares sinusóides (congestão). No rim materno, encontramos áreas eosinofílicas e núcleos hipercromáticos na parede dos túbulos contorcidos proximais. O fígado e rins maternos do Grupo Exp180 tiveram alterações morfológicas mais intensas do que no Grupo Exp60. Não observamos alterações histomorfológicas nos fígados e rins fetais em todos os grupos, o que pode ser decorrente da ação protetora da glicoproteína P. CONCLUSÕES: nossos resultados mostram que a administração de Ritonavir a ratas prenhes causou alterações morfológicas nos fígados e rins maternos em doses mais altas que a convencional. Já a ausência de anormalidades nos órgãos fetais pode ser explicada pelo papel protetor da glicoproteína P.Abstract PURPOSE: to evaluate the effect of the chronic administration of three different doses of Ritonavir in the liver and kidneys of pregnant albino rats and their concepts from a morphological standpoint. METHODS: forty pregnant albino EPM-1 Wistar rats were randomly divided into four groups: Contr (vehicle control), and three experimental groups, Exp20, Exp60, Exp180, which received daily 20, 60 or 180 mg/kg of Ritonavir, respectively. The drug and the vehicle (propyleneglycol) were orally administered by gavage, from the first up to the 20 th day of pregnancy. At the last experimental day, all the animals were sacrificed under deep anesthesia, and fragments from the maternal and fetal liver and kidneys were taken and prepared for histological analysis by light microscope. RESULTS: no morphological changes were identified in Exp20 and control group. In the Exp60 group, we found hepatocytes with signs of atrophy and apoptosis (eosinophilic cytoplasm and picnotic nuclei) and marked sinusoid capillary vasodilation (congestion). The proximal convoluted tubules of maternal kidneys and liver showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. The maternal kidneys and livers of the Exp180 rats presented more prominent morphological...

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