Browsing by Author "Neves, Pedro L."
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- Fracturing issue concerning cardiovascular mortality in chronic kidney disease patientsPublication . Mendes, Filipa; Silva, Ana P.; Alonso, Isis; Fragoso, André; Pereira, Luisa Helena; Jerónimo, Teresa; Pimentel, Ana; Neves, Pedro L.With the ageing of population worldwide, the riskof both osteoporosis and chronic kidney disease increased. These two conditions multiply the riskof bone fractures. The higher riskoffractures in CKD is accompanied bya higher mortality rate in hemodialysis patients. According to the Universityof Michigan’s study,the risk mortalityafter hip fracturewas 6.5 times higher in stage 5 CKD patients compared with patient with normal kidney function. In this study we analyzed the role of bone mineral metabolism and of hip fractures on cardiovascular mortality in a population of chronic kidney disease pre-dialysis patients. Methods: In an observational study, we included 300 patients followed in a pre-dialysis clinic during a 8 years period (2005-2013). Descriptive statistics and the Cox proportional hazard regression model were used to find risk factors of cardiovascular mortality.The mean age of these patients was 69.38 years, the mean eGFR (MDRD) was 20.40 ml/min and 60% (180) were female. Results: Using the Cox proportional hazard regression model, adjusted to age, gender, Diabetes Mellitus, Charlson comorbidity index, e-GFR, calcium, phosphorus, PTH, 25 OHD, osteocalcin, albumin and hip fractures, we found that25(OH)2D3 (HR= 0.950, 95% CI, 0.697 to 0.993 p=0.035), eGFR (HR= 0.638, 95% CI, 0.586 to 0.993, p=0.028) and hip fractures (HR= 1.753, 95% CI, 1.294 to 1.893 p=0.036) were independent risk factors of cardiovascular mortality. Conclusions: In our population of chronic kidney pre-dialysis patients, the levels of 25 (OH)2D3 and renal function, as well asthe presence of hip fractures increased the risk of cardiovascular mortality.
- Gla-Rich Protein Is a Novel Vitamin K-Dependent Protein Present in Serum That Accumulates at Sites of Pathological CalcificationsPublication . Viegas, Carla; Cavaco, Sofia; Neves, Pedro L.; Ferreira, Ana; Joao, Alexandre; Williamson, Matthew K.; Price, Paul A.; Cancela, M. Leonor; Simes, DinaMineralization of soft tissues is an abnormal process that occurs in any body tissue and can greatly increase morbidity and mortality. Vitamin K-dependent (VKD) proteins play a crucial role in these processes; matrix Gla protein is considered one of the most relevant physiological inhibitors of soft tissue calcification know to date. Several studies have suggested that other, still unknown, VKD proteins might also be involved in soft tissue calcification pathologies. We have recently identified in sturgeon a new VKD protein, Gla-rich protein (GRP), which contains the highest ratio between number of Gla residues and size of the mature protein so far identified. Although mainly expressed in cartilaginous tissues of sturgeon, in rat GRP is present in both cartilage and bone. We now show that GRP is a circulating protein that is also expressed and accumulated in soft tissues of rats and humans, including the skin and vascular system in which, when affected by pathological calcifications, GRP accumulates at high levels at sites of mineral deposition, indicating an association with calcification processes. The high number of Gla residues and consequent mineral binding affinity properties strongly suggest that GRP may directly influence mineral formation, thereby playing a role in processes involving connective tissue mineralization. (Am J Pathol 2009, 175:2288-2298; DOI; 10.2353/ajpath.2009.090474)
- Gla-Rich protein, magnesium and phosphate associate with mitral and aortic valves calcification in Didabetic patients with moderate CKDPublication . Silva, Ana P.; Viegas, Carla; Guilherme, Patrícia; Tavares, Nelson; Dias, Carolina; Rato, Fátima; Santos, Nélio; Faísca, Marília; de Almeida, Edgar; Neves, Pedro L.; Simes, Dina C.Accelerated and premature cardiovascular calcification is a hallmark of chronic kidney disease (CKD) patients. Valvular calcification (VC) is a critical indicator of cardiovascular disease and all-cause mortality in this population, lacking validated biomarkers for early diagnosis. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor recently associated with vascular calcification, pulse pressure, mineral metabolism markers and kidney function. Here, we examined the association between GRP serum levels and mitral and aortic valves calcification in a cohort of 80 diabetic patients with CKD stages 2–4. Mitral and aortic valves calcification were detected in 36.2% and 34.4% of the patients and associated with lower GRP levels, even after adjustments for age and gender. In this pilot study, univariate, multivariate and Poisson regression analysis, show that low levels of GRP and magnesium (Mg), and high levels of phosphate (P) are associated with mitral and aortic valves calcification. Receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) values of GRP for mitral (0.762) and aortic (0.802) valves calcification were higher than those of Mg and P. These results suggest that low levels of GRP and Mg, and high levels of P, are independent and cumulative risk factors for VC in this population; the GRP diagnostic value might be potentially useful in cardiovascular risk assessment.
- Risk factors of hip fractures in chronic kidney disease patientsPublication . Mendes, Filipa; Gomes, Ana; Alonso, Isis; Fragoso, André; Pereira, Luisa Helena; Jerónimo, Teresa; Pimentel, Ana; Neves, Pedro L.In the Western World the general population is getting older. This implies a higher prevalence of osteoporosis as well as a greater incidence of patients with chronic kidney disease. These two conditions increase the riskof bone fractures. Metabolic and hormonal disarrangement in end-stage renal disease (ESRD) negativelyaffects bone remodeling as it promotes a decrease in Vitamin D availability, hyperphosphatemia, hypocalcemia, high secretion of parathormone and chronic metabolic acidosis. The NHANES III showed that even moderate-to-severe CKD patients may present with a significant increased riskoffracturewhich is justified by hyperparathyroidism at the earlystages of the disease.
- The effect of paricalcitolon dialysate protein loss in peritoneal dialysis patientsPublication . Jerónimo, Teresa; del Peso, Gloria; Gayo, Lucia; Guedes, A. Malho; Silva, Ana P.; Neves, Pedro L.; Selgas, Rafael; Bajo, Maria A.Ever since peritoneal dialysis (PD) has been used in the treatment of chronic kidney disease (CKD), high peritoneal protein loss has been observed on each PD exchange. In adult patients, the loss has been estimated at 6 to 13 g daily. Paricalcitol, a selective activator of vitamin D receptors (VDR), is successfully used as a treatment of hyperparathyroidism secondary to CKD. In addition, it has been proposed for reducing proteinuria in patients with CKD. Nonetheless, little is known about its effect on peritoneal protein loss (PPL) in patients on PD, namely after the identification of VDRon the peritoneal membrane. The aim of this study wasto examine the effect of paricalcitol on PPL in PD patients.