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- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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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.
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| 2. |
- Nascimento, M. M., et al.
(författare)
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Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease
- 2014
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Ingår i: Brazilian journal of medical and biological research. - 0100-879X .- 1414-431X. ; 47:11, s. 995-1002
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Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG) regulates bone mass by inhibiting osteoclast differentiation and activation, and plays a role in vascular calcification. We evaluated the relationship between osteoprotegerin levels and inflammatory markers, atherosclerosis, and mortality in patients with stages 3-5 chronic kidney disease. A total of 145 subjects (median age 61 years, 61% men; 36 patients on hemodialysis, 55 patients on peritoneal dialysis, and 54 patients with stages 3-5 chronic kidney disease) were studied. Clinical characteristics, markers of mineral metabolism (including fibroblast growth factor-23 [FGF-23]) and inflammation (high-sensitivity C-reactive protein [hsCRP] and interleukin-6 [IL-6]), and the intima-media thickness (IMT) in the common carotid arteries were measured at baseline. Cardiac function was assessed by color tissue Doppler echocardiography. After 36 months follow-up, the survival rate by Kaplan-Meier analysis was significantly different according to OPG levels (chi(2) = 14.33; P = 0.002). Increased OPG levels were positively associated with IL-6 (r = 0.38, P<0.001), FGF-23 (r = 0.26, P<0.001) and hsCRP (r = 0.0.24, P = 0.003). In addition, OPG was positively associated with troponin I (r = 0.54, P<0.001) and IMT (r = 0.39, P<0.0001). Finally, in Cox analysis, only OPG (HR = 1.07, 95% CI = 1.02-1.13) and hsCRP (HR = 1.02, 95% CI = 1.01-1.04) were independently associated with increased risk of death. These results suggested that elevated levels of serumOPG might be associated with atherosclerosis and all-cause mortality in patients with chronic kidney disease.
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| 3. |
- Yamamoto, T., et al.
(författare)
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Changes in circulating biomarkers during a single hemodialysis session
- 2013
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Ingår i: Hemodialysis International. - : Wiley. - 1492-7535 .- 1542-4758. ; 17:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- The hemodialysis (HD) procedure induces an inflammatory response potentially contributing to cardiovascular disease. Here we investigated the acute impact of HD on circulating biomarkers. Circulating biomarkers (small solutes, middle molecular-sized peptides, and proteins) related to inflammation, oxidative stress, and vascular calcification (VC) were measured before and after a single session of HD in 45 clinically stable patients. Concentrations were corrected for ultrafiltration-induced hemoconcentration. Among vascular calcification-related biomarkers, osteoprotegerin and fetuin-A remained unchanged while fibroblast growth factor-23 (FGF23) decreased by -19%. Changes of FGF23 and changes of phosphate correlated (ρ=0.61, P<0.001). While C-reactive protein did not change, interleukin-6 (IL-6) increased by 14% and pentraxin 3 (PTX3) increased by 45%. IL-6 and PTX3 appear to be valid biomarkers of the intradialytic inflammatory response. VC-related markers were in general not affected by the single HD session; however, the observed correlation between acute changes of FGF-23 and phosphate during HD warrants further studies.
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| 7. |
- Grahl, DA, et al.
(författare)
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Associations between the CYBA 242C/T and the MPO -463G/A polymorphisms, oxidative stress and cardiovascular disease in chronic kidney disease patients
- 2007
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Ingår i: Blood purification. - : S. Karger AG. - 1421-9735 .- 0253-5068. ; 25:2, s. 210-218
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variations in the NADPH/MPO system in chronic kidney disease (CKD) patients might lead to altered activity of these enzymes, and thus to altered risk for oxidative stress (OS) and cardiovascular disease (CVD). We evaluated the impact of 242C/T <i>CYBA</i> and –463G/A <i>MPO</i> polymorphisms on OS and CVD mortality in stage 5 CKD patients starting dialysis. Two hundred and fifty-seven patients were genotyped using Pyrosequencing. Plasmalogen [dimethylacetal (DMA) 16/C16:0] was used as OS marker. CVD was assessed from patient history and clinical symptoms. Prevalence of CVD was higher (35%) in GG patients (<i>MPO</i>) compared to AG (26%) and AA (0%) patients (p < 0.01). Patients with CC genotype (<i>CYBA</i>) had lower levels of DMA 16/C16:0 (ratio 0.071 ± 0.003) compared to TT patients (0.089 ± 0.006; p < 0.05). These patients also had increased CVD mortality compared to CT and TT patients (χ<sup>2</sup> 2.19; p < 0.05). We conclude that genetic variations in the NADPH/MPO system are associated with OS, presence of CVD and CVD-related mortality in CKD patients.
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| 14. |
- Kalantar-Zadeh, Kamyar, et al.
(författare)
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Nomenclature in nephrology : preserving renal and nephro in the glossary of kidney health and disease
- 2021
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Ingår i: JN. Journal of Nephrology. - : SPRINGER HEIDELBERG. - 1121-8428 .- 1724-6059. ; 34:3, s. 639-648
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Tidskriftsartikel (refereegranskat)abstract
- A recently published nomenclature by a "Kidney Disease Improving Global Outcomes" (KDIGO) Consensus Conference suggested that the word "kidney" should be used in medical writings instead of "renal" or "nephro" when referring to kidney disease and kidney health. Whereas the decade-old move to use "kidney" more frequently should be supported when communicating with the public-at-large, such as the World Kidney Day, or in English speaking countries in communications with patients, care-partners, and non-medical persons, our point of view is that "renal" or "nephro" should not be removed from scientific and technical writings. Instead, the terms can coexist and be used in their relevant contexts. Cardiologists use "heart" and "cardio" as appropriate such as "heart failure" and "cardiac care units" and have not replaced "cardiovascular" with "heartvessel", for instance. Likewise, in nephrology, we consider that "chronic kidney disease" and "continuous renal replacement therapy" should coexist. We suggest that in scientific writings and technical communications, the words "renal" and "nephro" and their derivatives are more appropriate and should be freely used without any pressure by medical journals to compel patients, care-partners, healthcare providers, researchers and other stakeholders to change their selected words and terminologies. We call to embrace the terms "kidney", "renal" and "nephro" as they are used in different contexts and ask that scientific and medical journals not impose terminology restrictions for kidney disease and kidney health. The choice should be at the discretion of the authors, in the different contexts including in scientific journals.
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| 16. |
- Nascimento, MM, et al.
(författare)
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Effect of oral N-acetylcysteine treatment on plasma inflammatory and oxidative stress markers in peritoneal dialysis patients: a placebo-controlled study
- 2010
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Ingår i: Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. - : SAGE Publications. - 1718-4304 .- 0896-8608. ; 30:3, s. 336-342
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation and oxidative stress (OS) are cardiovascular risk factors in patients with chronic kidney disease. N-acetylcysteine (NAC) is a thiol-containing antioxidant with anti-inflammatory properties and has been shown to reduce the number of cardiovascular events in hemodialysis patients. ♦ Methods The current study aimed to determine the effect of oral NAC (2 × 600 mg/daily) on plasma levels of inflammatory and OS markers in peritoneal dialysis (PD) patients. We performed a placebo-controlled study over 8 weeks in 30 patients (40% males, age 52 ± 13 years) on regular PD. Before the study was started, the patients were divided into 2 groups of 15 patients matched for age and gender. 22 patients completed the study (12 on NAC, 10 on placebo). Proinflammatory cytokines [high-sensitivity C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-alpha, and pentraxin 3] and markers of OS (pentosidine, advanced oxidation protein products, homocysteine, glutathione, asymmetric dimethylarginine, and free sulfhydryls) were measured before and after treatment with NAC. ♦ Results Treatment with NAC for 8 weeks increased mean baseline plasma NAC levels from 2.6 to 24.8 μmol/L ( p = 0.007). This intervention, which caused no side effects, significantly diminished IL-6 levels, from 9.4 (4.5 – 31) to 7.6 (4.9 – 13.5) pg/mL ( p = 0.006), whereas no such changes were observed in the placebo group. NAC treatment did not significantly affect the other inflammatory and OS markers. ♦ Conclusions Short-term oral NAC treatment resulted in reduction of circulating IL-6, suggesting that such treatment could be a useful strategy in blunting the inflammatory response in PD patients.
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