Eubicarbonatemic Hydrogen Retention and CKD Progression

Abstract Background and Aims Chronic kidney disease (CKD) is a syndrome that today has important implications for the health of populations and the economic sustainability of health systems around the world, therefore strategies to slow disease progression are necessary. Aims: To estimate the incidence of renal replacement therapy (RRT) in a cohort of patients included in a CKD secondary prevention program and to describe the decrease of the estimated glomerular filtration rate (eGFR). Method This is a historical, multicenter, observational cohort study in a prevention program between January 1, 2010, and December 31, 2017, with follow-up until December 31, 2018, at the Renal Care Services (RCS) network. Socio-demographic and clinical characteristics of all patients were summarized descriptively. We estimated the incidence of RRT rate with Kaplan Meier analysis. Progression rate to RRT was analyzed by mixed-effects model adjusted for the eGFR reduction rate at 180 days; the model considered the diagnosis of diabetes. Results 7131 patients met the inclusion criteria for data analysis. The mean age was 65 years, 50.5% were female, (Table 1). There were 577 events of RRT with a rate of 2.02 events of RRT per 100 patients-year [95% CI,1.86 to 2.19], characteristics at the RRT initiation are presented in Table 2. At the beginning of the program the eGFR was 45.3 ml / min / 1.73m2 in non-diabetics, and 40.9 3 ml / min / 1.73m2 in diabetics. The CKD progression was - 0.48 ml / min / 1.73m2 per 180 days in diabetics and - 0.20 ml / min / 1.73m2 per 180 days in non-diabetics. The final events of the cohort are presented in Figure 1; the mortality rate was 0.89 events per 100 patients-year [95% CI, 0,79 to 1,01]. Conclusion This population of patients in a CKD prevention program presented a low rate of initiation of dialysis therapy and a slight decrease of eGFR; the diabetic status influences the CKD progression.

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Improving the W Coating Uniformity by a COMSOL Model-Based CVD Parameter Study for Denser Wf/W Composites

Metals ◽

10.3390/met11071089 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1089

Author(s):

Leonard Raumann ◽

Jan Willem Coenen ◽

Johann Riesch ◽

Yiran Mao ◽

Daniel Schwalenberg ◽

...

Keyword(s):

Relative Density ◽

Gas Flow ◽

Chemical Vapor ◽

Process Time ◽

Parameter Study ◽

Reactor Model ◽

Production Route ◽

Coating Uniformity ◽

Hydrogen Retention ◽

Return Lead

Tungsten (W) has the unique combination of excellent thermal properties, low sputter yield, low hydrogen retention, and acceptable activation. Therefore, W is presently the main candidate for the first wall and armor material for future fusion devices. However, its intrinsic brittleness and its embrittlement during operation bears the risk of a sudden and catastrophic component failure. As a countermeasure, tungsten fiber-reinforced tungsten (Wf/W) composites exhibiting extrinsic toughening are being developed. A possible Wf/W production route is chemical vapor deposition (CVD) by reducing WF6 with H2 on heated W fabrics. The challenge here is that the growing CVD-W can seal gaseous domains leading to strength reducing pores. In previous work, CVD models for Wf/W synthesis were developed with COMSOL Multiphysics and validated experimentally. In the present article, these models were applied to conduct a parameter study to optimize the coating uniformity, the relative density, the WF6 demand, and the process time. A low temperature and a low total pressure increase the process time, but in return lead to very uniform W layers at the micro and macro scales and thus to an optimized relative density of the Wf/W composite. High H2 and low WF6 gas flow rates lead to a slightly shorter process time and an improved coating uniformity as long as WF6 is not depleted, which can be avoided by applying the presented reactor model.

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Circulating Renalase as Predictor of Renal and Cardiovascular Outcomes in Pre-Dialysis CKD Patients: A 5-Year Prospective Cohort Study

Life ◽

10.3390/life11030210 ◽

2021 ◽

Vol 11 (3) ◽

pp. 210

Author(s):

Ana Cerqueira ◽

Janete Quelhas-Santos ◽

Inês Ferreira ◽

Susana Sampaio ◽

Miguel Relvas ◽

...

Keyword(s):

Cardiovascular Risk ◽

Hospital Admissions ◽

Univariate Analysis ◽

Serum Levels ◽

Ckd Progression ◽

Renal Outcomes ◽

Cerebrovascular Events ◽

All Cause Mortality ◽

Comorbidity Index

Chronic kidney disease (CKD) is an independent risk factor for adverse cardiovascular and cerebrovascular events (MACCEs), and mortality since the earlier stages. Therefore, it is critical to identify the link between CKD and cardiovascular risk (CVR) through early and reliable biomarkers. Acknowledging that CKD and CKD progression are associated with increased sympathetic tone, which is implicated in CVR, and that renalase metabolizes catecholamines, we aimed to evaluate the relationship between renalase serum levels (RNLS) and cardiovascular and renal outcomes. The study included 40 pre-dialysis CKD patients (19F:21M) with median age of 61 (IQ 45–66) years. At baseline, we measured RNLS as well as routine biomarkers of renal and cardiovascular risk. A prospective analysis was performed to determine whether RNLS are associated with CKD progression, MACCEs, hospitalizations and all-cause mortality. At baseline, the median level of RNLS and median estimated glomerular filtration rate (eGFR) were 63.5 (IQ 48.4–82.7) µg/mL and 47 (IQ 13–119) mL/min/1.73 m2, respectively. In univariate analysis, RNLS were strongly associated with eGFR, age and Charlson Index. Over the course of a mean follow-up of 65 (47 to 70) months, 3 (7.5%) deaths, 2 (5%) fatal MACCEs, 17 (42.5%) hospital admissions occurred, and 16 (40%) patients experienced CKD progression. In univariate analysis, RNLS were associated with CKD progression (p = 0.001), hospitalizations (p = 0.001) and all-cause mortality (p = 0.022) but not with MACCEs (p = 0.094). In adjusted analysis, RNLS predicted CKD progression and hospitalizations regardless of age, Charlson comorbidity index, cardiovascular disease, hypertension, diabetes and dyslipidemia. Our results suggest that RNLS, closely related with renal function, might have a potential role as predictor of renal outcomes, hospitalizations, and mortality in pre-dialysis CKD patients.

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Protective Role of Nrf2 in Renal Disease

Antioxidants ◽

10.3390/antiox10010039 ◽

2020 ◽

Vol 10 (1) ◽

pp. 39

Author(s):

Melania Guerrero-Hue ◽

Sandra Rayego-Mateos ◽

Cristina Vázquez-Carballo ◽

Alejandra Palomino-Antolín ◽

Cristina García-Caballero ◽

...

Keyword(s):

Oxidative Stress ◽

Current Knowledge ◽

Unmet Need ◽

Kidney Injury ◽

Protective Role ◽

Renal Diseases ◽

Related Factor ◽

Ckd Progression ◽

Protective Mechanisms ◽

Novel Therapeutic Strategies

Chronic kidney disease (CKD) is one of the fastest-growing causes of death and is predicted to become by 2040 the fifth global cause of death. CKD is characterized by increased oxidative stress and chronic inflammation. However, therapies to slow or prevent CKD progression remain an unmet need. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that plays a key role in protection against oxidative stress and regulation of the inflammatory response. Consequently, the use of compounds targeting Nrf2 has generated growing interest for nephrologists. Pre-clinical and clinical studies have demonstrated that Nrf2-inducing strategies prevent CKD progression and protect from acute kidney injury (AKI). In this article, we review current knowledge on the protective mechanisms mediated by Nrf2 against kidney injury, novel therapeutic strategies to induce Nrf2 activation, and the status of ongoing clinical trials targeting Nrf2 in renal diseases.

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Progressive Reduction in Mitochondrial Mass Is Triggered by Alterations in Mitochondrial Biogenesis and Dynamics in Chronic Kidney Disease Induced by 5/6 Nephrectomy

Biology ◽

10.3390/biology10050349 ◽

2021 ◽

Vol 10 (5) ◽

pp. 349

Author(s):

Rodrigo Prieto-Carrasco ◽

Fernando E. García-Arroyo ◽

Omar Emiliano Aparicio-Trejo ◽

Pedro Rojas-Morales ◽

Juan Carlos León-Contreras ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Mitochondrial Biogenesis ◽

Renal Mass ◽

Renal Damage ◽

Peroxisome Proliferator ◽

Progressive Reduction ◽

Ckd Progression ◽

Peroxisome Proliferator Activated Receptor ◽

Mitochondrial Mass ◽

Mitochondrial Impairment

The five-sixth nephrectomy (5/6Nx) model is widely used to study the mechanisms involved in chronic kidney disease (CKD) progression. Mitochondrial impairment is a critical mechanism that favors CKD progression. However, until now, there are no temporal studies of the change in mitochondrial biogenesis and dynamics that allow determining the role of these processes in mitochondrial impairment and renal damage progression in the 5/6Nx model. In this work, we determined the changes in mitochondrial biogenesis and dynamics markers in remnant renal mass from days 2 to 28 after 5/6Nx. Our results show a progressive reduction in mitochondrial biogenesis triggered by reducing two principal regulators of mitochondrial protein expression, the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and the peroxisome proliferator-activated receptor alpha. Furthermore, the reduction in mitochondrial biogenesis proteins strongly correlates with the increase in renal damage markers. Additionally, we found a slow and gradual change in mitochondrial dynamics from fusion to fission, favoring mitochondrial fragmentation at later stages after 5/6Nx. Together, our results suggest that 5/6Nx induces the progressive reduction in mitochondrial mass over time via the decrease in mitochondrial biogenesis factors and a slow shift from mitochondrial fission to fusion; both mechanisms favor CKD progression in the remnant renal mass.

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Risk Factors for CKD Progression

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.07830520 ◽

2020 ◽

pp. CJN.07830520

Author(s):

Mary Hannan ◽

Sajid Ansari ◽

Natalie Meza ◽

Amanda H. Anderson ◽

Anand Srivastava ◽

...

Keyword(s):

Risk Factors ◽

Genome Wide Association Study ◽

Healthy Lifestyle ◽

Interdisciplinary Collaboration ◽

Fibroblast Growth Factor 23 ◽

Kidney Injury ◽

The United States ◽

Future Research ◽

Ckd Progression ◽

Factors Associated

The Chronic Renal Insufficiency Cohort (CRIC) Study is an ongoing, multicenter, longitudinal study of nearly 5500 adults with CKD in the United States. Over the past 10 years, the CRIC Study has made significant contributions to the understanding of factors associated with CKD progression. This review summarizes findings from longitudinal studies evaluating risk factors associated with CKD progression in the CRIC Study, grouped into the following six thematic categories: (1) sociodemographic and economic (sex, race/ethnicity, and nephrology care); (2) behavioral (healthy lifestyle, diet, and sleep); (3) genetic (apoL1, genome-wide association study, and renin-angiotensin-aldosterone system pathway genes); (4) cardiovascular (atrial fibrillation, hypertension, and vascular stiffness); (5) metabolic (fibroblast growth factor 23 and urinary oxalate); and (6) novel factors (AKI and biomarkers of kidney injury). Additionally, we highlight areas where future research is needed, and opportunities for interdisciplinary collaboration.

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