Bone remodeling after renal transplantation

Bone remodeling after renal transplantation. Several studies have indicated that bone alterations after transplantation are heterogeneous. Short-term studies after transplantation have shown that many patients exhibit a pattern consistent with adynamic bone disease. In contrast, patients with long-term renal transplantation show a more heterogeneous picture. Thus, while adynamic bone disease has also been described in these patients, most studies show decreased bone formation and prolonged mineralization lag-time faced with persisting bone resorption, and even clear evidence of generalized or focal osteomalacia in many patients. Thus, the main alterations in bone remodeling are a decrease in bone formation and mineralization up against persistent bone resorption, suggesting defective osteoblast function, decreased osteoblastogenesis, or increased osteoblast death rates. Indeed, recent studies from our laboratory have demonstrated that there is an early decrease in osteoblast number and surfaces, as well as in reduced bone formation rate and delayed mineralization after transplantation. These alterations are associated with an early increase in osteoblast apoptosis that correlates with low levels of serum phosphorus. These changes were more frequently observed in patients with low turnover bone disease. In contrast, PTH seemed to preserve osteoblast survival. The mechanisms of hypophosphatemia in these patients appear to be independent of PTH, suggesting that other phosphaturic factors may play a role. However, further studies are needed to determine the nature of a phosphaturic factor and its relationship to the alterations of bone remodeling after transplantation

Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells

Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. Hypertension is a major complication of rHuEPO therapy in hemodialysis (HD) patients. We have previously reported that patients receiving rHuEPO intravenously (i.v.) had higher mean arterial pressure (MAP) and plasma endothelin-1 (ET-1) levels than those in which the hormone was administered subcutaneously (s.c). To test whether the increased serum ET-1 levels associated with i.v. rHuEPO administration are the result of a direct effect of the hormone on ET-1 release by the endothelial cells (EC), we examined the effects of rHuEPO in vitro. Bovine pulmonary artery endothelial cells (BPAEC) were exposed to doses of rHuEPO of 0.8; 1.6; 3.3 and 6.6 U/ml. A 24 hour-time course showed maximal ET-1 production at 12 hours for all the doses tested. A significant increase in cell proliferation over controls was observed at 24 hours, for all rHuEPO doses, and no correlation was found between ET-1 values and cell proliferation. Inhibition of protein synthesis by cycloheximide (10 µg/ml) abolished the stimulation of ET-1 release by rHuEPO. Thrombin (4 U/ml) and angiotensin II (10-7 M), two potent stimulators of ET-1 release, had additive effects to those of rHuEPO. Specific thrombin and angiotensin II antagonists blocked these additive effects, reducing ET-1 release to the level of rHuEPO stimulation alone. In summary, rHuEPO stimulates vascular EC in culture to increase ET-1 release through an increase in synthesis and in a time dependent fashion. The routes of stimulation seem to differ from other known ET-1 secretogoges. Our data also confirm a significant mitogenic effect of rHuEPO on the endothelial cell

The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling

The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling.BackgroundLoss of bone mass after transplantation begins in the early periods after transplantations and may persist for several years, even in patients with normal renal function. While the pathogenesis of these abnormalities is still unclear, several studies suggest that preexisting bone disease, glucocorticoid therapy, and alterations in phosphate metabolism may play important roles. Recent studies indicate that osteoblast apoptosis and impaired osteoblastogenesis play important roles in the pathogenesis of glucocorticoid-induced osteoporosis.ObjectivesTo examine the early alterations in osteoblast number and surfaces during the period following renal transplantation.MethodsTwenty patients with a mean age of 36.5 ± 12 years were subjected to bone biopsy 22 to 160 days after renal transplantation. In 12 patients, a control biopsy was performed on the day of transplantation. Bone sections were evaluated by histomorphometric analysis and cell DNA fragmentation by the methods of terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL), using immunoperoxidase and direct immunofluorescence techniques.ResultsThe main alterations in posttransplant biopsies were a decrease in osteoid and osteoblast surfaces, adjusted bone formation rate, and prolonged mineralization lag time. Peritrabecular fibrosis was markedly decreased. None of the pretransplant biopsies revealed osteoblast apoptosis. In contrast, TUNEL-positive cells in the proximity of osteoid seams or in the medullary space were observed in nine posttransplant biopsies of which four had mixed bone disease, two had adynamic bone disease, one had osteomalacia, one had osteitis fibrosa, and one had mild hyperparathyroid bone disease. Osteoblast number in posttransplant biopsies with apoptosis was lower as compared with posttransplant biopsies without apoptosis. In addition, most of them showed a marked shift toward quiescence from the cuboidal morphology of active osteoblasts. Serum phosphorus levels were lower in patients showing osteoblast apoptosis and correlated positively with osteoblast number and negatively with the number of apoptotic osteoblasts. In addition, posttransplant osteoblast surface correlated positively with parathyroid hormone (PTH) levels and negatively with glucocorticoid cumulative dose.ConclusionThe data suggest that impaired osteoblastogenesis and early osteoblast apoptosis may play important roles in the pathogenesis of posttransplant osteoporosis. The possible mechanisms involved in the pathogenesis of theses alterations include posttransplant hypophosphatemia, the use of glucocorticoids, and the preexisting bone disease. PTH seems to have a protective effect by preserving osteoblast survival

Sustainable Development Goals relevant to kidney health: an update on progress

Globally, more than 5 million people die annually from lack of access to critical treatments for kidney disease - by 2040, chronic kidney disease is projected to be the fifth leading cause of death worldwide. Kidney diseases are particularly challenging to tackle because they are pathologically diverse and are often asymptomatic. As such, kidney disease is often diagnosed late, and the global burden of kidney disease continues to be underappreciated. When kidney disease is not detected and treated early, patient care requires specialized resources that drive up cost, place many people at risk of catastrophic health expenditure and pose high opportunity costs for health systems. Prevention of kidney disease is highly cost-effective but requires a multisectoral holistic approach. Each Sustainable Development Goal (SDG) has the potential to impact kidney disease risk or improve early diagnosis and treatment, and thus reduce the need for high-cost care. All countries have agreed to strive to achieve the SDGs, but progress is disjointed and uneven among and within countries. The six SDG Transformations framework can be used to examine SDGs with relevance to kidney health that require attention and reveal inter-linkages among the SDGs that should accelerate progress

Sustainable Development Goals relevant to kidney health : an update on progress

Globally, more than 5 million people die annually from lack of access to critical treatments for kidney disease - by 2040, chronic kidney disease is projected to be the fifth leading cause of death worldwide. Kidney diseases are particularly challenging to tackle because they are pathologically diverse and are often asymptomatic. As such, kidney disease is often diagnosed late, and the global burden of kidney disease continues to be underappreciated. When kidney disease is not detected and treated early, patient care requires specialized resources that drive up cost, place many people at risk of catastrophic health expenditure and pose high opportunity costs for health systems. Prevention of kidney disease is highly cost-effective but requires a multisectoral holistic approach. Each Sustainable Development Goal (SDG) has the potential to impact kidney disease risk or improve early diagnosis and treatment, and thus reduce the need for high-cost care. All countries have agreed to strive to achieve the SDGs, but progress is disjointed and uneven among and within countries. The six SDG Transformations framework can be used to examine SDGs with relevance to kidney health that require attention and reveal inter-linkages among the SDGs that should accelerate progress. Working towards sustainable development is essential to tackle the rise in the global burden of non-communicable diseases, including kidney disease. Five years after the Sustainable Development Goal agenda was set, this Review examines the progress thus far, highlighting future challenges and opportunities, and explores the implications for kidney disease

Uso de álcool entre adolescentes escolares: um estudo-piloto

O uso de álcool entre adolescentes é um tema que preocupa profissionais da saúde pelos prejuízos acarretados e pela displicência da sociedade quanto ao uso desta droga por essa faixa etária. Este artigo analisa o consumo de álcool entre alunos do ensino médio de três escolas de Cascavel-PR. O instrumento utilizado foi o Alcohol Use Disordens Identification Test (AUDIT), além de levantamento de informações sobre o nível socioeconômico, religião e o beber problemático de familiar. O resultado mostrou que 34,7% dos estudantes bebem de maneira arriscada, não havendo diferenças significativas por escola, gênero e nível socioeconômico. Ter familiar que bebe foi considerado fator de risco e ter religião, fator protetor. Esta pesquisa pode alertar a sociedade paranaense para a necessidade de estudos mais amplos, com o objetivo de desenvolver políticas públicas que incluam projetos de prevenção e intervenção dirigidos à população jovem