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- Klotho levels: association with insulin resistance and albumin-to-creatinine ratio in type 2 diabetic patientsPublication . Silva, Ana Paula; Mendes, Filipa; Pereira, Luisa; Fragoso, André; Baptista Gonçalves, Rui; Santos, Nelio; Rato, Fátima; Neves, Pedro LeãoThe present study aimed at evaluating the relationship between Klotho levels and insulin resistance and albumin-to-creatinine ratio (ACR) in type 2 diabetic patients with CKD. We conducted an observational, cross-sectional study in our outpatient diabetic nephropathy clinic from 2014 to 2016, enrolling a total of 107 type 2 diabetic patients with stage 2-3 CKD, with a mean age of 59 years. Several clinical and laboratorial parameters were evaluated, including those related to mineral and carbohydrate metabolism. The mean eGFR at baseline was 53.2 mL/min, and the mean levels of ACR and Klotho were 181.9 A mu g/mg and 331.1 pg/m, respectively. In the simple linear regression model, Klotho levels were correlated with age, phosphorus, PTH, ACR, HOMA, IL-6, FGF-23, OxLDL, eGFR and vitamin D levels. Applying a multivariate linear regression model, only the ACR, HOMA-IR, FGF-23 and vitamin D independently influenced the Klotho levels. In the generalized linear model, only the Klotho groups were statistically significant as independent variable (p = 0.007). The results show that the group 1 (< 268) compared with group 3 (> 440) had higher odds in the higher ACR (ae181), ORa = 3.429, p = 0.014. There were no statistically significant differences between Klotho groups 2 and 3, and the HOMA-IR obtained showed that group 1 (< 268) had greater odds of HOMA-IR ae2 when compared with group 3 (> 440), ORa = 21.59, p = 0.017. Our results showed that Klotho levels are influenced by FGF23, vitamin D and insulin resistance. This suggests that Klotho levels might be affected by renal function as well as having a relevant role on insulin metabolism and ACR homeostasis.
- 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.
- Angels and demons regarding cardiovascular disease in diabetic renal patients: the role of FGF-23 Andklotho on the pulse pressurePublication . Silva, Ana Paula; Mendes, Filipa; Fragoso, André; Santos, Nélio; Rato, Fátima; Faísca, Marilia; Neves, Pedro LeãoThe last decade have shown thatFGF23 and Klotho may have relevant independent actions on the renal and cardiovascular systems. Theyinterfere with vascular functions and may playa role in vascularcalcification, atherosclerosis and arteriolosclerosis. On the other hand, pulse pressureis awell-known risk factorof cardiovascular morbidityand mortality in renal patients. The aim of this study isto investigate the relationship between FGF-23 and Klothowith pulse pressure in type 2 diabetic with chronic kidney disease (CKD) stages 2-3.
- Risk factors for fractures in type 2 diabetic with chronic kidney disease stage: the saints and the sinnersPublication . Gomes, Ana; Mendes, Filipa; Fragoso, André; Santos, Nélio; Rato, Fátima; Faísca, Marília; Neves, Pedro LeãoSince the population in the developed world is aging, the burden offragility fractures is aconstantly increasing problem. Despite the fact that potent bone-specific pharmaceutical agents have become available, the problem of how to identify patients with high fracture risk yet remains an enigma. Some studies mention the role of a normal mineral metabolism is critical for skeletal development and preservation of bone integrity. The aim of this study isto investigate the association of mineralmetabolism with hip fractures in type 2 diabetic with chronic kidney disease (CKD).
- Altered serum levels of FGF-23 and magnesium are independent risk factors for an increased albumin-to-creatinine ratio in type 2 diabetics with chronic kidney diseasePublication . Silva, Ana Paula; Mendes, Filipa; Fragoso, André; Jerónimo, Teresa; Pimentel, Ana; Gundlach, Kristina; Büchel, Janine; Santos, Nélio; Neves, Pedro LeãoAims: To investigate the role of FGF-23 and magnesium in relation to the albumin-to-creatinine ratio in type 2 diabetics with chronic kidney disease (CKD) stages 2-4.Methods: In a cross-sectional study we included all eligible type 2 diabetic patients with CKD stages 2-4, followed in our outpatient Diabetic Kidney clinic. We used descriptive statistics, the Student's t-test, ANOVA and the chi-square tests. Our population was divided according to the UACR (G1 30-300 mg/g and G2 >= 300 mg/g), and compared these groups regarding several biological and laboratorial parameters. We employed a multiple regression model to identify risk factors of increased UACR.Results: The patients in G2 displayed a lower eGFR (p = 0.0001) and, had lower levels of magnesium (p = 0.004) as well as higher levels of FGF-23 (p = 0.043) compared to patients in Gl.FGF-23 (beta = 0.562, P = 0.0001) and the magnesium (beta = - 8.916, p = 0.0001) were associated with increased UACR.Conclusions: A dysregulation of mineral metabolism, reflected by altered levels of magnesium and FGF-23, correlates with an increased UACR in type 2 diabetic patients with CKD stages 2-4. (C) 2016 Elsevier Inc. All rights reserved.
- 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.
- Plasmatic Klotho and FGF23 levels as biomarkers of CKD-associated cardiac disease in type 2 diabetic patientsPublication . Silva, Ana Paula; Mendes, Filipa; Carias, Eduarda; Baptista Gonçalves, Rui; Fragoso, André; Dias, Carolina; Tavares, Nelson; Mendonça Café, Hugo; Santos, Nélio; Rato, Fátima; Neves, Pedro Leão; Almeida, EdgarResearch over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality.