Genetic variants of interferon lambda-related genes and chronic kidney disease susceptibility in the Korean population

Background Chronic kidney disease (CKD) is a common condition leading to renal dysfunction and is closely related to increased cardiovascular and mortality risk. CKD is an important public health issue, and recent genetic studies have verified common CKD susceptibility variants. This research examines the interrelationship between candidate genes polymorphisms of interferon lambda (IFNL) induction, its signaling pathway, and CKD. Methods Seventy-five patients with advanced CKD and 312 healthy subjects (as controls) participated in this research. A replication set composed of 172 patients with advanced CKD and 365 controls was used for additional analysis. The genotype of single nucleotide polymorphisms (SNPs) was determined by the Axiom Genome-Wide Human Assay and SNaPshot assay. Results The SNP of IFNL3 was significantly associated with CKD in the codominant (p = 0.02) and dominant models (p = 0.02). In addition, the SNPs of IFNL2 were significantly associated with CKD in the dominant model (p = 0.03), and the SNP of interferon alpha receptor 2 (IFNAR2) was significantly associated with CKD in the log-additive model (p = 0.03). Concerning rs148543092, in the IFNL3 gene, a significant association was observed after pooling the original and replication sets. Conclusion These results indicate that SNPs in the IFNL induction and signal pathway may be associated with CKD risk in the Korean population. Finally, our results also show that the IFNL3 gene variant may be associated with CKD risk

Late Simultaneous Presentation of Left Ventricular Pseudoaneurysm and Tricuspid Regurgitation after Blunt Chest Trauma

A 32-yr-old man developed progressive exertional dyspnea 4 yr after blunt chest trauma due to an automobile accident. Two-dimensional echocardiography and computed-tomographic coronary angiography demonstrated a large pseudoaneurysm of the left ventricle and severe tricuspid regurgitation. The patient underwent successful surgical exclusion of the pseudoaneurysm by endoaneurysmal patch closure and repair of the tricuspid valve regurgitation. To the best of our knowledge, this is the first case of these 2 different pathologies presenting late simultaneously after blunt chest trauma and successful surgical repairs in the published literature

First snapshot on behavioral characteristics and related factors of patients with chronic kidney disease in South Korea during the COVID-19 pandemic (June to October 2020)

Background The recent novel coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented changes in behavior. We evaluated the current status of precautionary behavior and physical activity in chronic kidney disease (CKD) patients during the COVID-19 pandemic. Methods A population of CKD patients (n = 306) registered in the Study on Kidney Disease and Environmental Chemicals (SKETCH, Clinical Trial No. NCT04679168) cohort recruited from June 2020 to October 2020 was included in the study. We conducted a questionnaire survey related to risk perception of COVID-19, precautionary behavior, and physical activity. Results There were 187 patients (61.1%) with estimated glomerular filtration rate of <45 mL/min/1.73 m2. This population showed a higher degree of risk perception for COVID-19 than the general population. Age was the most significant determinant of risk perception among CKD patients. During the pandemic, social distancing and hygiene-related behavior were significantly increased (p < 0.001). The frequency of exercise was decreased only in those who took regular exercise, without diabetes, or with a lower Charlson comorbidity index (CCI) (p < 0.001), with no change among the other groups. Socioeconomic status and comorbidities significantly affected behavioral characteristics regardless of the category. Education and income were significantly associated with precautionary behaviors such as staying at home and hand sanitizer use. Patients with higher CCI status significantly increased frequency of exercise (adjusted odds ratio, 2.10; 95% confidence interval, 1.01–4.38). Conclusion CKD patients showed higher risk perception with active precautionary behavioral changes than the general population. Healthcare providers should be aware of the characteristics to comprise precautionary behavior without reducing physical activity

Salt-sensitive hypertension in mitochondrial superoxide dismutase deficiency is associated with intra-renal oxidative stress and inflammation.

BackgroundRenal interstitial inflammation and oxidative stress are invariably present and play a key role in the pathogenesis of hypertension in experimental animals. Mitochondria are the major source of reactive oxygen species (ROS). ROS generated in the mitochondria are normally contained by the mitochondrial antioxidant system including manganese superoxide dismutase (MnSOD). We have previously shown that a high salt diet causes hypertension in MnSOD-deficient (MnSOD(+/-)) mice but not in wild-type mice. The present study was undertaken to determine the effect of a high salt diet on oxidative and inflammatory pathways in the kidneys of MnSOD(+/-) mice compared to the wild-type mice.MethodsWild-type (MnSOD(+/+)) and MnSOD(+/-) mice were randomized to receive a regular or a high salt diet for 4 months. Tail arterial pressure was measured and timed urine collection was obtained. The animals were then euthanized and the kidneys were harvested and processed for histological examination and Western blot analyses.ResultsIn confirmation of our earlier study, a high salt diet resulted in a significant rise in arterial pressure and urinary albumin excretion in MnSOD(+/-) mice. This was accompanied by upregulation of NAD(P)H oxidase subunits, activation of nuclear factor kappa B, and elevation of PAI-1, iNOS, oxidized LDL receptor, and CD36 in the kidneys of the MnSOD(+/-) mice fed the high salt diet. In contrast, consumption of a high salt diet did not significantly alter blood pressure, urine protein excretion, or the measured oxidative and inflammatory mediators in the wild-type mice.ConclusionSalt-induced hypertension in MnSOD(+/-) mice is associated with activation of intra-renal inflammatory and ROS generating pathways

Salt-sensitive hypertension in mitochondrial superoxide dismutase deficiency is associated with intra-renal oxidative stress and inflammation.

BackgroundRenal interstitial inflammation and oxidative stress are invariably present and play a key role in the pathogenesis of hypertension in experimental animals. Mitochondria are the major source of reactive oxygen species (ROS). ROS generated in the mitochondria are normally contained by the mitochondrial antioxidant system including manganese superoxide dismutase (MnSOD). We have previously shown that a high salt diet causes hypertension in MnSOD-deficient (MnSOD(+/-)) mice but not in wild-type mice. The present study was undertaken to determine the effect of a high salt diet on oxidative and inflammatory pathways in the kidneys of MnSOD(+/-) mice compared to the wild-type mice.MethodsWild-type (MnSOD(+/+)) and MnSOD(+/-) mice were randomized to receive a regular or a high salt diet for 4 months. Tail arterial pressure was measured and timed urine collection was obtained. The animals were then euthanized and the kidneys were harvested and processed for histological examination and Western blot analyses.ResultsIn confirmation of our earlier study, a high salt diet resulted in a significant rise in arterial pressure and urinary albumin excretion in MnSOD(+/-) mice. This was accompanied by upregulation of NAD(P)H oxidase subunits, activation of nuclear factor kappa B, and elevation of PAI-1, iNOS, oxidized LDL receptor, and CD36 in the kidneys of the MnSOD(+/-) mice fed the high salt diet. In contrast, consumption of a high salt diet did not significantly alter blood pressure, urine protein excretion, or the measured oxidative and inflammatory mediators in the wild-type mice.ConclusionSalt-induced hypertension in MnSOD(+/-) mice is associated with activation of intra-renal inflammatory and ROS generating pathways

Elevated Plasma Cyclophillin A in Hemodialysis and Peritoneal Dialysis Patients: a Novel Link to Systemic Inflammation.

IntroductionCyclophillin A has emerged as a novel mediator of oxidative stress and inflammation and a major player in cardiovascular disease, diabetes mellitus, viral infections, and neurodegenerative and thrombotic disorders. Cyclophillin A is released by certain cell types spontaneously or in response to inflammatory mediators, hypoxia, oxidative stress, and hyperglycemia. Many of these conditions are either present or frequently occur in patients with end-stage renal disease and can stimulate release of cyclophillin A, thereby amplifying systemic inflammation. To our knowledge, the effect of end-stage renal disease and dialysis modalities on circulating cyclophillin A has not been previously investigated. This study tested the hypothesis that extracellular cyclophillin A is elevated in patients maintained on hemodialysis and peritoneal dialysis.Materials and methodsCyclophillin A, high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and lipid levels were measured in the fasting plasma samples from 20 hemodialysis and 20 peritoneal dialysis patients, and 20 age- and sex-matched controls.ResultsPlasma cyclophillin A concentration in the patients on hemodialysis (105.3 ± 6.2 ng/mL) and peritoneal dialysis (106.8 ± 9.0 ng/mL) were significantly higher than that in the control group (29.7 ± 4.1 ng/mL). This was associated with significant elevation of high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α. Plasma cyclophillin A concentration showed direct correlations with high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α, and an inverse correlation with high-density lipoprotein cholesterol concentration.ConclusionsPlasma cyclophillin A concentration is markedly elevated and positively correlates with the markers of systemic inflammation in hemodialysis and peritoneal dialysis patients

Dysregulation of hepatic fatty acid metabolism in chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) results in hypertriglyceridemia which is largely due to impaired clearance of triglyceride-rich lipoproteins occasioned by downregulation of lipoprotein lipase and very low-density lipoprotein (LDL) receptor in the skeletal muscle and adipose tissue and of hepatic lipase and LDL receptor-related protein in the liver. However, data on the effect of CKD on fatty acid metabolism in the liver is limited and was investigated here. METHODS: Male Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy (CRF) or sham operation (control) and observed for 12 weeks. The animals were then euthanized and their liver tissue tested for nuclear translocation (activation) of carbohydrate-responsive element binding protein (ChREBP) and sterol-responsive element binding protein-1 (SREBP-1) which independently regulate the expression of key enzyme in fatty acid synthesis, i.e. fatty acid synthase (FAS) and acyl-CoA carboxylase (ACC) as well as nuclear Peroxisome proliferator-activated receptor alpha (PPARα) which regulates the expression of enzymes involved in fatty acid oxidation and transport, i.e. L-FABP and CPT1A. In addition, the expression of ATP synthase α, ATP synthase β, glycogen synthase and diglyceride acyltransferase 1 (DGAT1) and DGAT2 were determined. RESULTS: Compared with controls, the CKD rats exhibited hypertriglyceridemia, elevated plasma and liver tissue free fatty acids, increased nuclear ChREBP and reduced nuclear SREBP-1 and PPARα, upregulation of ACC and FAS and downregulation of L-FABP, CPT1A, ATP synthase α, glycogen synthase and DGAT in the liver tissue. CONCLUSION: Liver in animals with advanced CKD exhibits ChREBP-mediated upregulation of enzymes involved in fatty acid synthesis, downregulation of PPARα-regulated fatty acid oxidation system and reduction of DGAT resulting in reduced fatty acid incorporation in triglyceride