Effect Of Chronic Kidney Disease Research Articles

Household Water Lead and Hematologic Toxic Effects in Chronic Kidney Disease.

The consequences of low levels of environmental lead exposure, as found commonly in US household water, have not been established. To examine whether commonly encountered levels of lead in household water are associated with hematologic toxicity among individuals with advanced kidney disease, a group known to have disproportionate susceptibility to environmental toxicants. Cross-sectional analysis of household water lead concentrations and hematologic outcomes was performed among patients beginning dialysis at a Fresenius Medical Care outpatient facility between January 1, 2017, and December 20, 2021. Data analysis was performed from April 1 to August 15, 2023. Concentrations of lead in household water were examined in categorical proportions of the Environmental Protection Agency's allowable threshold (15 μg/L) and continuously. Hematologic toxic effects were defined by monthly erythropoiesis-stimulating agent (ESA) dosing during the first 90 days of incident kidney failure care and examined as 3 primary outcomes: a proportion receiving maximum or higher dosing, continuously, and by a resistance index that normalized to body weight and hemoglobin concentrations. Secondarily, hemoglobin concentrations for patients with data prior to kidney failure onset were examined, overall and among those with concurrent iron deficiency, thought to increase gastrointestinal absorption of ingested lead. Among 6404 patients with incident kidney failure (male, 4182 [65%]; mean [SD] age, 57 [14] years) followed up for the first 90 days of dialysis therapy, 12% (n = 742) had measurable lead in household drinking water. A higher category of household lead contamination was associated with 15% (odds ratio [OR], 1.15 [95% CI, 1.04-1.27]) higher risk of maximum monthly ESA dosing, 4.5 (95% CI, 0.8-8.2) μg higher monthly ESA dose, and a 0.48% (95% CI, 0.002%-0.96%) higher monthly resistance index. Among patients with pre-kidney failure hemoglobin measures (n = 2648), a higher household lead categorization was associated with a 0.12 (95% CI, -0.23 to -0.002) g/dL lower hemoglobin concentration, particularly among those with concurrent iron deficiency (multiplicative interaction, P = .07), among whom hemoglobin concentrations were 0.25 (95% CI, -0.47 to -0.04) g/dL lower. The findings of this study suggest that levels of lead found commonly in US drinking water may be associated with lead poisoning among susceptible individuals.

#1755 Cardio-protective effect of soy proteins during long-term consumption of Cynomolgus Monkeys high-saline diet

Abstract Background and Aims High salt intake is accompanied by the development of cardiovascular disorders, not always associated with an increase in blood pressure (BP). Recently, it has been found that the introduction of soy protein into the diet can have some nephroprotective and cardioprotective effects in chronic kidney disease. Considering the cardioprotective effect of soy proteins in chronic kidney disease, the question arose about the possibility of using soy proteins to neutralize the damaging effect of a high-salt diet on the cardiovascular system. This work aims to study the effect of long-term use of a diet high in NaCl and soy protein on myocardial remodeling in monkeys. Method The study was performed on male Macaca fascicularis. The animals were divided into three groups (6 animals each), comparable in weight and age (6-8 years, body weight - 5.15-9.7 kg). The control group received a standard diet (2 g NaCl/kg feed). The second was a high salt diet (8 g NaCl/kg feed), and the third was a high salt diet and SUPRO760 soy protein (200 g/kg feed). Echocardiography (EchoCG), registration of BP and heart rate were performed at baseline, after 4 and 12 months. EchoCG was performed with a sector transducer with a frequency of 3–5 MHz on the Chison SonoTouch 60 ultrasound system (China). EchoCG was performed in B_mode (two-dimensional scanning), M_mode (one-dimensional scanning), as well as in pulse and tissue Doppler modes. Statistical analysis was performed using parametric statistics: mixed ANOVA in comparing data from 3 study groups (with post hoc analysis using Tukey criterion) and single factor variance analysis for related samples in studying the dynamics of one or another index in each group during the 12-month follow-up. Differences were considered significant at p < 0.05. Results In animals of all three groups for 12 months, blood pressure (BPsis-109±10.09, BPdias – 60 ± 7.42 mm Hg) and heart rate (77 ± 12.61 min-1) did not change significantly (p>0. 05). However, in macaques on a high-salt diet, deterioration in left ventricular (LV) systolic and diastolic function was noted by the end of the study. Macaques of this group had a decrease in the LV shortening fraction (27.9±2.69%) and an increase in the thickness of the posterior wall of the LV in systole (0.69±0.039 cm), LV mass (19.60±2.83 g), compared with animals additionally receiving soy proteins (34.9±6.57%; 0.57 0.0559 cm; 14.86±2.94 g, respectively; all p < 0.05). In addition, the monkeys receiving soy isolate did not differ from the control in these parameters. By the time the study was completed, the animals in this group had significantly increased the magnitude of systolic excursion of the mitral annulus plane, and signs of improvement in LV diastolic function appeared in the form of an increase in the maximum rate of excursion of the mitral valve fibrous annulus in early diastole, as well as a decrease in the E/e' ratio. The thickness of the interventricular septum also decreased (0.42±0.04 cm; in the high-salt group - 0.51±0.08 cm), which can be interpreted as a sign of positive myocardial remodeling. Conclusion Thus, high salt intake leads to adverse structural and functional disorders of the heart in cynomolgus monkeys, not associated with an increase in blood pressure. The inclusion of soy isolate in the diet reduces the negative effects of a high-salt diet on the cardiovascular system.

Navigating challenges: insights into chronic kidney disease care in South Auckland

The burden of chronic kidney disease is increasing throughout New Zealand, resulting in growing strain on patients, families and the healthcare system. The population of South Auckland is the most diverse in New Zealand and it is particularly vulnerable to the effects of chronic kidney disease due to its demography and its many communities that endure significant hardships. This article explores the prevailing challenges identified by renal physicians and nurse specialists over 35 years of caring for patients with chronic kidney disease in South Auckland.

Chronic Kidney Disease affects Thyroid Hormones

Kidney disease is one of the causes of death in many countries around the world. This study found that chronic kidney disease affects thyroid hormone formation, release, and storage. The results show a decrease in T3 and T4 thyroid hormones and an increase in TSH hormone in both sexes and people of different ages. The research aims to study the effect of chronic kidney disease on the thyroid gland’s activity and its deficiency’s effect on health ailments. Results showed a significant decrease in T3 concentration in patients at the probability level (p ≤ 0.05) (0.8±0.1) compared with the control group (1.0±0.1). Additionally, a significant decrease in T4 concentration at the probability level (p ≤ 0.05), (6.8±1.5) compared with the control group (8.7±0.9) and a significant increase in TSH concentration at the probability level (p ≤ 0.05), (4.8±0.6) compared with the control group (1.2±0.5). The CDK affects thyroid hormones; low T3 and T4 are the most common thyroid dysfunction. High TSH, enlarged thyroid gland, hypothyroidism, thyroid dysfunction. Keywords: CKD, Thyroid Hormones, Thyroid dysfunction.

Effect of chronic kidney disease induced calcification on peripheral vascular perfusion using near-infrared spectroscopic imaging.

Low-cost techniques that can detect the presence of vascular calcification (VC) in chronic kidney disease (CKD) patients could improve clinical outcomes. In this study, we established a near-infrared spectroscopy-based imaging technique to determine changes in peripheral hemodynamics due to CKD-induced VC. Mice were fed a high-adenine diet with either normal or high levels of phosphate to induce CKD with and without VC, respectively. The mice tail was imaged to evaluate hemodynamic changes in response to occlusion. The rate of change in oxyhemoglobin in response to occlusion showed a statistically significant difference in the presence of VC in the mice.

Development of 4-Pyridoxic Acid PBPK Model to Support Biomarker-Informed Evaluation of OAT1/3 Inhibition and Effect of Chronic Kidney Disease.

Monitoring endogenous biomarkers is increasingly used to evaluate transporter-mediated drug-drug interactions (DDIs) in early drug development and may be applied to elucidate changes in transporter activity in disease. 4-pyridoxic acid (PDA) has been identified as the most sensitive plasma endogenous biomarker of renal organic anion transporters (OAT1/3). Increase in PDA baseline concentrations was observed after administration of probenecid, a strong clinical inhibitor of OAT1/3 and also in patients with chronic kidney disease (CKD). The aim of this study was to develop and verify a physiologically-based pharmacokinetic (PBPK) model of PDA, to predict the magnitude of probenecid DDI and predict the CKD-related changes in PDA baseline. The PBPK model for PDA was first developed in healthy population, building on from previous population pharmacokinetic modeling, and incorporating a mechanistic kidney model to consider OAT1/3-mediated renal secretion. Probenecid PBPK model was adapted from the Simcyp database and re-verified to capture its dose-dependent pharmacokinetics (n = 9 studies). The PBPK model successfully predicted the PDA plasma concentrations, area under the curve, and renal clearance in healthy subjects at baseline and after single/multiple probenecid doses. Prospective simulations in severe CKD predicted successfully the increase in PDA plasma concentration relative to healthy (within 2-fold of observed data) after accounting for 60% increase in fraction unbound in plasma and additional 50% decline in OAT1/3 activity beyond the decrease in glomerular filtration rate. The verified PDA PBPK model supports future robust evaluation of OAT1/3 DDI in drug development and increases our confidence in predicting exposure and renal secretion in patients with CKD.

Effects of Chronic Kidney Disease on Transcatheter Aortic Valve Replacement Outcomes in Low-Flow Low-Gradient Aortic Stenosis

Effects of Chronic Kidney Disease on Transcatheter Aortic Valve Replacement Outcomes in Low-Flow Low-Gradient Aortic Stenosis

Abstract P197: The Total And Direct Effects Of Cardiovascular Risk Factors On Target Organ Injury And The Indirect Effect Mediated Through Blood Pressure Severity: Modifying Effect Of Chronic Kidney Disease

Youth-onset chronic kidney disease (CKD) is associated with early development of increased cardiovascular (CV) disease risk. CV health factors (CVHF) such as obesity, dyslipidemia, and hyperglycemia contribute to CV risk, but their specific role in target organ injury (TOI) development in youth with CKD is not well understood. Our objective was to determine the modifying effect of CKD on the total and direct effects of CVHF on TOI and the indirect effect mediated through blood pressure (BP) severity in youth with HTN disorders, hypothesizing that CKD would increase the mediating role of BP. Interim cross-sectional analysis of baseline data from the SUPERHERO Registry, a multisite retrospective registry of EHR data from youth referred for HTN disorders. Diagnoses were defined by ICD-10 codes unless otherwise specified. Inclusion criteria were age <19 years and HTN disorder from 1/1/2015-12/31/2022 at initial subspecialty clinic visit. Exclusion criteria were dialysis, kidney transplantation, or pregnancy. Presence of 0-3 CVHF defined our exposure: any combination of obesity (by BMI %ile), dyslipidemia, or hyperglycemia. Outcome was TOI (kidney and/or heart). Mediator was BP by HTN severity (defined by U.S. pediatric guidelines). Total and direct effects of CVHF on TOI and indirect effect mediated via HTN were analyzed using generalized linear models and causal mediation analysis adjusted for unmet social needs and participant home region, stratified by CKD. Of 11580 participants, 488 (4%) had a CKD diagnosis. Presence of only 1 CVHF was associated with lower odds of TOI overall in youth without CKD (OR 0.69, 95% CL 0.59, 0.81) but higher odds in youth with CKD (OR 1.7, 95% CL 0.98, 2.8), interaction term p <0.05. Presence of 2 CVHF was associated with higher odds of overall TOI (OR 1.53; 95% CL 1.14, 2.04) and heart-/kidney-specific TOI (OR 1.45 to 1.92). We found low prevalence of 3 CVHF and heart-specific TOI. We found no evidence of BP mediation or interaction for overall or organ-specific TOI. Our findings may be due to differences in kidney TOI between youth with and without CKD, reliance on ICD-10 codes, or different practices for TOI surveillance in youth with CKD. Future ongoing steps include analyzing laboratory and echocardiogram results for precision.

Chronic Kidney Disease Has No Impact on Tear Film Substance P Concentration in Type 2 Diabetes.

The study aimed to ascertain the potential effects of chronic kidney disease (CKD) on substance P concentration in the tear film of people with type 2 diabetes. Participants were classified into two groups: type 2 diabetes with concurrent chronic kidney disease (T2DM-CKD (n = 25)) and type 2 diabetes without chronic kidney disease (T2DM-no CKD (n = 25)). Ocular surface discomfort assessment, flush tear collection, in-vivo corneal confocal microscopy, and peripheral neuropathy assessment were conducted. Enzyme-linked immunosorbent assays were utilized to ascertain the levels of tear film substance P in collected flush tears. Correlation analysis, hierarchical multiple linear regression analysis, and t-tests or Mann-Whitney U tests were used in the analysis of data for two-group comparisons. There was no substantial difference between the T2DM-CKD and T2DM-no CKD groups for tear film substance P concentration (4.4 (0.2-50.4) and 5.9 (0.2-47.2) ng/mL, respectively; p = 0.54). No difference was observed in tear film substance P concentration between the low-severity peripheral neuropathy and high-severity peripheral neuropathy groups (4.4 (0.2-50.4) and 3.3 (0.3-40.7) ng/mL, respectively; p = 0.80). Corneal nerve fiber length (9.8 ± 4.6 and 12.4 ± 3.8 mm/mm2, respectively; p = 0.04) and corneal nerve fiber density (14.7 ± 8.5 and 21.1 ± 7.0 no/mm2, respectively; p < 0.01) were reduced significantly in the T2DM-CKD group compared to the T2DM-no CKD group. There were significant differences in corneal nerve fiber density (21.0 ± 8.1 and 15.8 ± 7.7 no/mm2, respectively; p = 0.04) and corneal nerve fiber length (12.9 ± 4.2 and 9.7 ± 3.8 mm/mm2, respectively; p = 0.03) between the low- and high-severity peripheral neuropathy groups. In conclusion, no significant difference in tear film substance P concentration was observed between type 2 diabetes with and without CKD. Corneal nerve loss, however, was more significant in type 2 diabetes with chronic kidney disease compared to type 2 diabetes alone, indicating that corneal nerve morphological measures could serve greater utility as a tool to detect neuropathy and nephropathy-related corneal nerve changes.

The Effect of Hemodialysis on Spectral and Temporal Processing Abilities and Speech Perception in Noise among Individuals with Chronic Kidney Disease

Introduction: The effect of chronic kidney disease (CKD) on hearing is well documented in the literature. Several studies have investigated the effect of hemodialysis on the peripheral auditory system among individuals with CKD. However, studies investigating the effect of hemodialysis on speech perception and auditory processing abilities are limited. The present study investigated the effect of hemodialysis on few auditory processing abilities and speech perception in noise among adults with CKD. Methods: A total of 25 adults with CKD undergoing hemodialysis regularly participated in the study. Spectral ripple discrimination threshold (SRDT), gap detection threshold (GDT), amplitude-modulation detection threshold (AMDT), and speech recognition threshold in noise (SRTn) were measured before and after hemodialysis. Paired samples “t” test was carried out to investigate the effect of hemodialysis on thresholds. Results: Results showed a significant improvement for SRDT, GDT, AMDT, and SRTn after hemodialysis among individuals with CKD. Discussion: Hemodialysis showed a positive effect on speech perception in noise and auditory processing abilities among individuals with CKD.

Effect of Chronic Kidney Disease on the Mortality Rate of Patient with Sepsis

&lt;div&gt;&lt;p class="AbstractNormal"&gt;&lt;strong&gt;Introduction&lt;/strong&gt;: Sepsis is a deathly disease caused by a dysregulation of the body's response to infection. The mortality rate of sepsis has been discovered to be almost equivalent to 20% of the global mortality rate. Comorbidity is one of the non-modifiable risk factors of sepsis. Chronic kidney disease is a comorbid risk factor for sepsis development. Decreasing GFR and albuminuria in chronic kidney disease is strongly associated with an increased mortality rate due to infection. Sepsis with chronic kidney disease shows a higher SOFA score than sepsis without chronic kidney disease. This study aims to determine the effect of chronic kidney disease on the mortality rate of patients with sepsis.&lt;/p&gt;&lt;p class="AbstractNormal"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This study is an observational analytic study with a cross-sectional approach. The data retrieval used purposive sampling, and the sample comprised 90 respondents. Data were taken from medical records of the patients with sepsis hospitalized in Dr Moewardi Hospital from January 2016 to May 2021. Data were analyzed using the Chi-Square test.&lt;/p&gt;&lt;p class="AbstractNormal"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Chronic kidney disease significantly affected the sepsis mortality rate with p-value = 0.033 (p &amp;lt; 0.05). The prevalence ratio was 2.531 (95%CI, 1.07 – 5.97).&lt;/p&gt;&lt;p class="AbstractNormal"&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Chronic kidney disease significantly affects the increasing mortality rate of sepsis patients.&lt;/p&gt;Keywords: Chronic kidney disease; Mortality; Sepsis,&lt;/div&gt;

Studi Literatur: Disfungsi Seksual pada Pasien dengan Penyakit Ginjal Kronik Yang Menjalani Hemodialysis

One of the effects of chronic kidney disease is a decrease in sexual function due to long hemodialysis, where patients who undergo hemodialysis for a long time will experience an inability to enjoy sexual activity so that it has an impact on fulfilling their needs. sexuality and change the patient's sexuality pattern. Sexual dysfunction in female hemodialysis patients causes increased pain in women (dyspareunia) and difficulty in vaginal mucus, whereas in men it includes disorders of sexual desire, erectile dysfunction and premature ejaculation. The aim of this study was to review the extent of sexual function in chronic kidney disease patients undergoing hemodialysis. This type of research uses a Literature Review (LR) with a population of 69 journals, with a sample of 2 national journals and 13 international journals according to the inclusion criteria of international or national journals related to sexual dysfunction in hemodialysis patients, journals published in a span of 10 years (2010 - 2020) ) and the journal must be in full text. Evaluation of the feasibility of the data using the Joanna Brigs Institute (JBI) by filling in the critical appraisal tool checklist sheet. The results showed sexual dysfunction that occurs in men is found; dissatisfaction, avoidance, loss of energy, premature ejaculation and erectile dysfunction, impotence, does not last long during sexual activity, lack of excitement, and the condition of sperm mixed with blood. Whereas in women it is found; dissatisfaction, orgasm, decreased desire, lubrication, pain during intercourse, reluctance to engage in sexual activity, decreased desire and libido. It is hoped that this research will serve as a theoretical basis in the nursing process both applied and theoretically.

Statins in Chronic Kidney Disease-Effects on Atherosclerosis and Cellular Senescence.

Chronic kidney disease (CKD) is a serious health problem that can affect various systems in the human body. Renal failure promotes mechanisms of premature cellular aging and also features of generalized inflammation in the body, which translates into a close relationship between kidney dysfunction and cardiovascular disease (CVD). As kidney function deteriorates, cardiovascular risk and mortality increase in this group of patients. Oxidative stress and inflammation are two closely related processes that initiate a vicious cycle by activating each other. Together with aging, they represent the key factors that cause and exacerbate CVD in CKD. Patients with CKD are particularly vulnerable to the accumulation of aging endothelial cells, vascular smooth muscle and macrophages, increasing the risk of atherosclerosis. Several mechanisms are known that can lead to the progression of the aforementioned problems, such as the accumulation of uremic toxins, persistent inflammation, impaired lipid and electrolyte metabolism, nitric oxide (NO) deficiency, the increased production of reactive oxygen species (ROS) and damage to deoxyribonucleic acid (DNA) and mitochondria. According to research, we can distinguish a group of drugs that effectively counteract the negative effects of CKD-statins. This is a group of drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase and affect a number of cellular processes and pathways, resulting in the overall slowing of atherosclerosis and cellular aging.

#3406 CARDIOPROTECTIVE EFFECT OF SOY PROTEIN ON LONG-TERM HIGH-SALT DIET IN CYNOMOLGUS MONKEYS

Abstract Background and Aims A high salt content in the diet is one of the reasons for the increase in blood pressure (BP) and the development of cardiovascular disorders. However, high intake of sodium chloride does not always lead to an increase in blood pressure, but causes endothelial dysfunction and cardiac remodeling. It has been established that the introduction of soy products into the diet can have a nephro- and cardioprotective effect in chronic kidney disease. At the same time, it is not clear whether the damaging effect of a high-salt diet on the cardiovascular system can be offset by other dietary interventions, in particular, soy proteins. In this regard, the aim of the study was to study the effect of long-term use of diets with different content of sodium chloride and soy protein on myocardial remodeling in cynomolgus monkeys. Method A total of 18 cynomolgus male monkeys with age 6–8 years were studied. The animals were divided into three groups (six in each group). The first (control) group received the standard diet. The second group received the diet rich in common salt (8 g of NaCl/kg), and the third, the high salt diet in combination with soy protein SUPRO 760 (200 g/kg; Protеin Tеchnology Intеrnational, USA). Systolic (BP) and diastolic (BPd) blood pressure (BP) in monkeys was recorded by oscillometric method on a veterinary tonometer ML-410 VET (Microlux, Russia) under anesthesia. After registration of blood pressure, an echocardiographic study (EchoCG) was performed with a sector sensor with a frequency of 3-5 MHz on an ultrasound system Chison SonoTouch 60 (China). Echocardiography was performed in B-mode (two-dimensional scanning), M-mode (one-dimensional scanning), as well as in pulsed and tissue Doppler modes. Echocardiography and blood pressure measurements were performed at baseline, after 4 and 12 months of follow-up. Results BP values (group 1 - BPs: 109±10.09, BPd: 60±7.42; group 2 - BPs: 109±25.14, BPd: 57±11.86; group 3 - BPs: 101±8, 59, BPd: 57±6.92 mm Hg, all p&amp;gt;0.05) and heart rate (group 1 - 77±12.61, group 2 - 81±18.07, group 3-80±19.9 beats/min, all p&amp;gt;0.05) in macaques did not undergo significant changes over 12 months of the experiment in any of the groups. In group 1, there were also no significant changes in echocardiographic parameters. Group 2 monkeys showed no early changes in LV shortening fraction (FU) and ejection fraction (EF). However, after 12 months, FU decreased by an average of 26.6%, and EF by 12.8% compared with the indicator for a period of 4 months. In addition, the speed of the transmitral flow in early diastole (E) decreased by 19.1% compared with the baseline. Long-term intake of soy proteins prevented a decrease in LV FU in macaques on a high-salt diet. Its value was 25.1% greater than in group 2. In group 3 monkeys, after 12 months, the magnitude of systolic excursion of the mitral annulus plane and the maximum rate of excursion of the fibrous annulus of the mitral valve in early diastole (e') increased, the thickness of the interventricular septum in diastole decreased, and E/e' ratio. In group 3, the thickness of the posterior wall of the left ventricle decreased in systole (0.57±0.056 mm), the mass of the LV myocardium (14.9±2.94 g/m2), the average diameter of the base of the right ventricle (1.20±0.115 mm) compared with group 2 (0.69±0.040 mm, 19.6±2.83 g/m2, 1.40±0.111 mm, respectively; all p&amp;lt;0.01). Conclusion The obtained results can be considered as confirmation of the hypothesis that high consumption of sodium chloride leads to adverse structural and functional changes in the heart and blood vessels, not associated with an increase in blood pressure. The inclusion of isolated soy proteins in the diet is likely to reduce the effects of this negative impact. The specific mechanisms of this cardioprotective effect remain to be explored. Statistical analysis used One-way analysis of variance for unrelated samples when comparing the data of 3 studied groups and one-way analysis of variance for related samples when studying the dynamics of the indicator in each of the groups during 12 months of observation. Results are presented as mean ± standard deviation (M ± SD). Differences were considered significant at p&amp;lt;0.05.

Cardiovascular Protection of Aspirin in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis.

This is to evaluate aspirin's cardiovascular (CV) protective effect in chronic kidney disease (CKD) patients. We searched PubMed, Embase, Cochrane Library, and Web of Science (up to December 2022) for randomized controlled trials (RCTs) and observational studies comparing aspirin with placebo in CKD patients for the prevention of CV disease (CVD). Efficacy outcomes included CVD, heart failure, myocardial infarction, stroke, CV and all-cause mortality; safety outcomes included major bleeding, minor bleeding, and renal events. Six RCTs and 6 observational studies, including 35,640 participants, met the inclusion criteria and reported relevant CV outcomes, with a mean follow-up of 46.83 months. The pooled data showed aspirin had no significant preventive effect on CVD events (RR=1.03; 95% CI, 0.84-1.27). However, CV mortality was significantly reduced in the aspirin group (RR=0.74; 95% CI, 0.58-0.95). Furthermore, aspirin use did not increase the risk of major bleeding and renal events but significantly increased minor bleeding events (RR=2.11; 95% CI, 1.30-3.44). Renal events were significantly increased after sensitivity analysis (RR=1.10; 95% CI, 1.04-1.16). Aspirin did not prevent CV events, with a significantly increased risk of minor bleeding and renal events. Besides, aspirin use had no statistically significant reduction in the risk of all-cause mortality but had a statistically significant reduction in the risk of CV mortality.

The effect of chronic kidney disease on tissue formation of in situ tissue-engineered vascular grafts.

Vascular in situ tissue engineering encompasses a single-step approach with a wide adaptive potential and true off-the-shelf availability for vascular grafts. However, a synchronized balance between breakdown of the scaffold material and neo-tissue formation is essential. Chronic kidney disease (CKD) may influence this balance, lowering the usability of these grafts for vascular access in end-stage CKD patients on dialysis. We aimed to investigate the effects of CKD on in vivo scaffold breakdown and tissue formation in grafts made of electrospun, modular, supramolecular polycarbonate with ureido-pyrimidinone moieties (PC-UPy). We implanted PC-UPy aortic interposition grafts (n = 40) in a rat 5/6th nephrectomy model that mimics systemic conditions in human CKD patients. We studied patency, mechanical stability, extracellular matrix (ECM) components, total cellularity, vascular tissue formation, and vascular calcification in CKD and healthy rats at 2, 4, 8, and 12 weeks post-implantation. Our study shows successful in vivo application of a slow-degrading small-diameter vascular graft that supports adequate in situ vascular tissue formation. Despite systemic inflammation associated with CKD, no influence of CKD on patency (Sham: 95% vs CKD: 100%), mechanical stability, ECM formation (Sirius red+, Sham 16.5% vs CKD 25.0%-p:0.83), tissue composition, and immune cell infiltration was found. We did find a limited increase in vascular calcification at 12 weeks (Sham 0.08% vs CKD 0.80%-p:0.02) in grafts implanted in CKD animals. However, this was not associated with increased stiffness in the explants. Our findings suggest that disease-specific graft design may not be necessary for use in CKD patients on dialysis.

The effect of chronic kidney disease on cardiovascular outcomes in patients with DM 2

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Managing Metabolic Acidosis in Chronic Renal Diseases

One of the most common side effects of chronic kidney disease is metabolic acidosis (CKD). It is associated with the development of CKD and various other functional disorders. Metabolic acidosis can be a common complication associated with progressive loss of kidney function. The form can be a metabolic acidosis with a non-anion gap or metabolic acidosis with a high or mixed anion gap. Reduced kidney ability to maintain acid-base homeostasis results in acid accumulation, causing various complications such as decreased nutritional status such as wasting muscle-hypoalbuminemia, inflammation, uremic bone disease and its association with increased mortality. In addition to the side effects associated with acid retention, metabolic acidosis can also cause kidney damage, possibly through stimulation of adaptive mechanisms aimed at maintaining acid-base homeostasis in the event of decreased renal function. chronic kidney disease (CKD), and therefore offers an effective, safe and affordable reno-protective strategy. This paper will discuss the physiology and pathophysiology of acid-base homeostasis in CKD, namely the mechanism of metabolic acidosis capable of impairing kidney function, and its relation to the benefits of alkaline therapy. based on clinical trials

Managing Metabolic Acidosis in Chronic Renal Diseases

One of the most common side effects of chronic kidney disease is metabolic acidosis (CKD). It is associated with the development of CKD and various other functional disorders. Metabolic acidosis can be a common complication associated with progressive loss of kidney function. The form can be a metabolic acidosis with a non-anion gap or metabolic acidosis with a high or mixed anion gap. Reduced kidney ability to maintain acid-base homeostasis results in acid accumulation, causing various complications such as decreased nutritional status such as wasting muscle-hypoalbuminemia, inflammation, uremic bone disease and its association with increased mortality. In addition to the side effects associated with acid retention, metabolic acidosis can also cause kidney damage, possibly through stimulation of adaptive mechanisms aimed at maintaining acid-base homeostasis in the event of decreased renal function. chronic kidney disease (CKD), and therefore offers an effective, safe and affordable reno-protective strategy. This paper will discuss the physiology and pathophysiology of acid-base homeostasis in CKD, namely the mechanism of metabolic acidosis capable of impairing kidney function, and its relation to the benefits of alkaline therapy. based on clinical trials

Population pharmacokinetic modelling to characterize the effect of chronic kidney disease on tenofovir exposure after tenofovir alafenamide administration.

Tenofovir alafenamide is gradually replacing tenofovir disoproxil fumarate, both prodrugs of tenofovir, in HIV prevention and treatment. There is thus an interest in describing tenofovir pharmacokinetics (PK) and its variability in people living with HIV (PLWH) under tenofovir alafenamide in a real-life setting. To characterize the usual range of tenofovir exposure in PLWH receiving tenofovir alafenamide, while assessing the impact of chronic kidney disease (CKD). We conducted a population PK analysis (NONMEM®) on 877 tenofovir and 100 tenofovir alafenamide concentrations measured in 569 PLWH. Model-based simulations allowed prediction of tenofovir trough concentrations (Cmin) in patients having various levels of renal function. Tenofovir PK was best described using a one-compartment model with linear absorption and elimination. Creatinine clearance (CLCR, estimated according to Cockcroft and Gault), age, ethnicity and potent P-glycoprotein inhibitors were statistically significantly associated with tenofovir clearance. However, only CLCR appeared clinically relevant. Model-based simulations revealed 294% and 515% increases of median tenofovir Cmin in patients with CLCR of 15-29 mL/min (CKD stage 3), and less than 15 mL/min (stage 4), respectively, compared with normal renal function (CLCR = 90-149 mL/min). Conversely, patients with augmented renal function (CLCR > 149 mL/min) had a 36% decrease of median tenofovir Cmin. Kidney function markedly affects circulating tenofovir exposure after tenofovir alafenamide administration in PLWH. However, considering its rapid uptake into target cells, we suggest only a cautious increase of tenofovir alafenamide dosage intervals to 2 or 3 days only in case of moderate or severe CKD, respectively.