| 1. |
- Ruilope, LM, et al.
(författare)
-
Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
|
|
| 2. |
|
|
| 3. |
- Kocyigit, I, et al.
(författare)
-
Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1β Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension
- 2019
-
Ingår i: Cardiorenal medicine. - : S. Karger AG. - 1664-5502 .- 1664-3828. ; 9:6, s. 370-381
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background and Objectives:</i></b> Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via <i>IL-1β</i> activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, <i>HIF-1α</i> gene expression from whole blood and urine samples and <i>IL-1β</i>gene expression from whole blood were measured. <b><i>Methods:</i></b> One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for <i>HIF-1α</i> and <i>IL-1β</i> gene<i></i>expression by using quantitative real-time PCR. <b><i>Results:</i></b> There were significant differences in whole blood <i>HIF-1α</i>,<i> IL-1β</i> gene<i></i>expression, and serum<i></i>succinate levels between the ADPKD patients and the control subjects. Whole blood <i>HIF-1α</i>gene expression,<i> IL-1β</i> gene<i></i>expression, and serum<i></i>succinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (<i>p</i> < 0.05). Serum succinate levels and blood<i> IL-1β</i> gene<i></i>expression were increased in ADPKD patients with high levels of <i>HIF-1α gene</i>expression (<i>p</i> = 0.018 and <i>p</i> = 0.029, respectively). <b><i>Conclusions:</i></b> Increased age,<i></i>low eGFR, and <i>HIF-1α</i> and <i>IL-1β</i> gene<i></i>expressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Kocyigit, D., et al.
(författare)
-
Cholesterol efflux promoting function of high-density lipoproteins in calcific aortic valve stenosis
- 2021
-
Ingår i: Atherosclerosis Plus. - : Elsevier BV. - 2667-0909 .- 2667-0895. ; 44:October, s. 18-24
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Cholesterol efflux capacity is a functional property of high-density lipoproteins (HDL) reflecting the efficiency of the atheroprotective reverse cholesterol transport process in humans. Its relationship with calcific aortic valve stenosis (CAVS) has not been fully assessed yet. Methods: We evaluated HDL-CEC in a patient population with varying degrees of aortic valvular calcific disease, assessed using echocardiography and cardiac computed tomography. Measurement of biomarkers that reflect osteogenic and tissue remodeling, along with dietary and gut microbiota-derived metabolites were performed. Results: Patients with moderate-severe CAVS had significantly lower HDL-CEC compared to both control and aortic sclerosis subjects (mean: 6.09%, 7.32% and 7.26%, respectively). HDL-CEC displayed negative correlations with peak aortic jet velocity and aortic valve calcium score, indexes of CAVS severity (ρ = -0.298, p = 0.002 and ρ = -0.358, p = 0.005, respectively). In multivariable regression model, HDL-CEC had independent association with aortic valve calcium score (B: -0.053, SE: 0.014, p < 0.001), GFR (B: -0.034, SE: 0.012, p = 0.007), as well as with levels of total cholesterol (B: 0.018, SE: 0.005, p = 0.002). Conclusion: These results indicate an impairment of HDL-CEC in moderate-severe CAVS and may contribute to identify potential novel targets for CAVS management. © 2021 The Authors
|
|
| 9. |
|
|
| 10. |
- Kocyigit, I, et al.
(författare)
-
Early arterial stiffness and inflammatory bio-markers in normotensive polycystic kidney disease patients
- 2012
-
Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 36:1, s. 11-18
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> Cardiovascular disease is the main cause of morbidity and mortality in autosomal-dominant polycystic kidney disease (ADPKD) patients. To clarify temporal relationship between ADPKD, hypertension and the loss of renal function, we examined these factors in patients with early-stage ADPKD who did not yet have hypertension. <b><i>Methods:</i></b> Fifty patients with ADPKD (42% males, 36.6 ± 9.9 years, no blood pressure medication) and 50 healthy controls (44% males, 35.4 ± 6.4 years) were studied cross-sectionally. Pulse wave velocity (PWV), cardiac morphology and function, aortic elastic indexes, estimated glomerular filtration rate (eGFR), 24-hour ambulatory blood pressure, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and highly sensitive C-reactive protein (hs-CRP) were measured in all participants, using conventional methods. <b><i>Results:</i></b> Despite a normal blood pressure, aortic stiffness index and pulse wave velocity values were increased in patients compared to controls (6.8 ± 4.7 vs. 5.1 ± 3.3, p = 0.043 and 9.6 ± 1.3 vs. 5.8 ± 1.1 m/s, p < 0.001). In univariate analysis, IL-6, TNF-α, hs-CRP and eGFR were all significantly correlated with PWV. The independence of these correlations were analyzed in a regression model, and showed PWV to be significantly predicted by IL-6, TNF-α and hs-CRP. <b><i>Conclusion:</i></b> Increased arterial stiffness and pulse wave velocity are early manifestations of ADPKD appearing before hypertension or reduced eGFR. However, these vascular abnormalities are related to signs of systemic low grade inflammation, suggesting a common pathophysiological mechanism apparently present also in other vascular diseases but yet to be elucidated.
|
|
