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Background: Sepsis-associated acute kidney injury (SA-AKI) is a prominent sepsis complication, often resulting in adverse clinical outcomes. Hyperbaric oxygen therapy (HBOT), known for its anti-inflammatory characteristics, antioxidant effects, and ability to deliver high oxygen tension to hypo-perfused tissues, offers potential benefits for SA-AKI. This study investigated whether HBOT improved renal injury in sepsis and elucidated its underlying mechanisms., Methods: A lipopolysaccharide (LPS)-induced endotoxemia model was established using 8-week-old C57BL/6 mice. Thirty minutes post-LPS administration, a group of mice underwent HBOT at a 2.5 atmospheric pressure absolute with 100% oxygen for 60 minutes. After 24 hours, all mice were euthanized for measurements., Results: Our results demonstrated that HBOT effectively mitigated renal tubular cell apoptosis. Additionally, HBOT significantly reduced phosphorylated p53 proteins and cytochrome C levels, suggesting that HBOT may attenuate renal apoptosis by impeding p53 activation and cytochrome C release. Notably, HBOT preserved manganese-dependent levels of superoxide dismutase, an antioxidant enzyme, compared to the LPS group. Furthermore, transforming growth factor beta (TGF-β)/Smad4 and alpha smooth muscle actin expressions were significantly reduced in the LPS + HBOT group., Conclusion: An early single session of HBOT exhibited renoprotective effects in LPS-induced endotoxemia mice models by suppressing p53 activation and cytochrome C levels to mitigate apoptosis. The observed TGF-β decrease, downstream Smad expression reduction, and antioxidant capacity preservation following HBOT may contribute to these effects.

Background: Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme activity deficiency. Although glycosphingolipid analogs have been identified in the plasma or urine of patients with FD, there is a limited understanding of altered metabolomics profiles beyond the globotriaosylceramide accumulation in FD., Methods: Metabolomics study was performed for monitoring of biomarker and altered metabolism related with disease progression in serum and urine from male α-galactosidase A knockout mice and age-matched wild-type mice at 20 and 40 weeks. Profiling analysis for metabolites, including organic acids, amino acids, fatty acids, kynurenine pathway metabolites, and nucleosides in the serum and urine was performed using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry combined with star symbol patterns and partial least squares discriminant analysis (PLS-DA)., Results: A total of 27 and 23 metabolites from the serum and urine of Fabry mice were distinguished from those of wild-type mice, respectively, based on p-value (<0.05) and variable importance in projection scores (>1.0) of PLS-DA. In the serum, metabolites of the glutathione, glutathione disulfide, citrulline, and kynurenine pathways that are related to oxidative stress, nitric oxide biosynthesis, and inflammation were increased, whereas those involved in pyruvate and tyrosine metabolism and the tricarboxylic acid cycle were altered in the 20- and 40-week-old urine of FD model mice., Conclusion: Altered metabolic signatures associated with disease progression by oxidative stress, inflammation, nitric oxide biosynthesis, and immune regulation in the early and late stages of FD.

Background: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multipotent protein that plays essential roles in cellular responses to oxidative stress., Methods: To examine the role of APE1/Ref-1 in ischemia-reperfusion (I/R) injuries and hydrogen peroxide (H2O2)-induced renal tubular apoptosis, we studied male C57BL6 mice and human proximal tubular epithelial (HK-2) cells treated with H2O2 at different concentrations. The colocalization of APE1/Ref-1 in the proximal tubule, distal tubule, thick ascending limb, and collecting duct was observed with confocal microscopy. The overexpression of APE1/Ref-1 with knockdown cell lines using an APE1/Ref-1-specific DNA or small interfering RNA (siRNA) was used for the apoptosis assay. The promotor activity of nuclear factor kappa B (NF-κB) was assessed and electrophoretic mobility shift assay was conducted., Results: APE1/Ref-1 was predominantly localized to the renal tubule nucleus. In renal I/R injuries, the levels of APE1/Ref-1 protein were increased compared with those in kidneys subjected to sham operations. The overexpression of APE1/Ref-1 in HK-2 cells enhanced the Bax/Bcl-2 ratio as a marker of apoptosis. Conversely, the suppression of APE1/Ref-1 expression by siRNA in 1-mM H2O2-treated HK-2 cells decreased the Bax/Bcl-2 ratio, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and NF-κB. In HK-2 cells, the promoter activity of NF-κB increased following H2O2 exposure, and this effect was further enhanced by APE1/Ref-1 transfection., Conclusion: The inhibition of APE1/Ref-1 with siRNA attenuated H2O2-induced apoptosis through the modulation of mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 and the nuclear activation of NF-κB and proapoptotic factors.

Background: Insulin resistance is prevalent in chronic kidney disease and may accelerate the progression of chronic kidney disease. This study aimed to investigate whether insulin resistance is associated with the development of incident chronic kidney disease in a population with normal renal function., Methods: A total of 3,331 participants from a community-based cohort with normal renal function were prospectively analyzed. We determined the relationship of insulin resistance indices with the incident chronic kidney disease using the Cox proportional hazard model and Kaplan-Meier survival analysis., Results: During a mean follow-up of 11.03 ± 4.22 years, incident chronic kidney disease occurred in 414 participants (12.4%). The high homeostasis model assessment-insulin resistance level group had an increased risk of incident chronic kidney disease (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.13-1.74; p = 0.002) compared to the normal group after adjustment for age, sex, history of hypertension, body mass index, total cholesterol, alcohol drinking status, smoking status, and baseline estimated glomerular filtration rate. The risk of incident chronic kidney disease also increased with the lower quantitative insulin sensitivity check index level (HR, 0.62; 95% CI, 0.41-0.92; p = 0.02) and higher leptin-adiponectin ratio level (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006)., Conclusion: Higher insulin resistance indices are associated with the incidence of chronic kidney disease. Our data suggest that increased insulin resistance may be involved in the development of incident chronic kidney disease in a population with normal renal function.

Background: The medium cutoff (MCO) dialyzer increases the removal of several middle molecules more effectively than high-flux hemodialysis (HD). However, comparative data addressing the efficacy and safety of MCO dialyzers vs. postdilution hemodiafiltration (HDF) in Korean patients are lacking., Methods: Nine patients with chronic HD were included in this pre-post study. Patients underwent HD with an MCO dialyzer for 4 weeks, followed by a 2-week washout period using a high-flux dialyzer to minimize carryover effects, and then turned over to postdilution HDF for 4 weeks. Reduction ratios and differences in the uremic toxins before and after dialysis were calculated from the MCO dialysis, postdilution HDF, and high-flux HD. In the in vitro study, EA.hy926 cells were incubated with dialyzed serum., Results: Compared to postdilution HDF, the MCO dialyzer achieved significantly higher reduction ratios for larger middle molecules (myoglobin, kappa free light chain [κFLC], and lambda FLC [λFLC]). Similarly, the differences in myoglobin, κFLC, and λFLC concentrations before and after the last dialysis session were significantly greater in MCO dialysis than in postdilution HDF. The expression of Bax and nuclear factor κB was decreased in the serum after dialysis with the MCO dialyzer than with HDF., Conclusion: Compared with high-volume postdilution HDF, MCO dialysis did not provide greater removal of molecules below 12,000 Da, whereas it was superior in the removal of larger uremic middle molecule toxins in patients with kidney failure. Moreover, these results may be expected to have an anti-apoptotic effect on the human endothelium.

Background: Although multiple factors influence the risk of major adverse cardiovascular events (MACE), the effects of socioeconomic status on MACE in the presence and absence of renal dysfunction (RD) have not been comprehensively explored in Korea., Methods: We examined the effects of socioeconomic status on MACE in individuals with and without RD. The data of 44,473 Koreans from 2008 to 2017 were obtained from the Health Care Big Data Platform of the Ministry of Health and Welfare in Korea. Their socioeconomic status was assessed using a socioeconomic score (SES) based on marital status, education, household income, and occupation. The incidence of myocardial infarction (MI), stroke, and death was compared according to SES level (0-4). Multiple linear regression analysis was used to evaluate the hazard ratios and 95% confidence intervals for outcomes based on participant SES., Results: MI risk was only affected by education level. The participants' income, education, and SES affected their stroke risk, whereas death was associated with all four socioeconomic factors. The incidence of stroke and death increased as SES worsened (from 0 to 4). SES was positively related to risk of stroke and death in participants without RD. SES did not affect MI, stroke, or death in participants with RD., Conclusion: A low socioeconomic status is associated with risk of stroke and death, especially in individuals without RD.

Background: Urine chloride has recently been suggested as a biomarker of renal tubule function in patients with nondialysis chronic kidney disease (CKD), as low urinary chloride concentration is associated with an increased risk of CKD progression. We investigate the association between urinary chloride excretion and the progression of coronary artery calcification (CAC)., Methods: A total of 1,065 patients with nondialysis CKD were divided into tertiles by spot urine chloride-to-creatinine ratios. The 1st, 2nd, and 3rd tertiles were defined as low, moderate, and high urinary chloride excretion, respectively. The study outcome was CAC progression, which was defined as an increase in coronary artery calcium score of more than 200 Agatston units during the 4-year follow-up period., Results: Compared to moderate urinary chloride excretion, high urinary chloride excretion was associated with decreased risk of CAC progression (adjusted odds ratio, 0.379; 95% confidence interval, 0.190-0.757), whereas low urinary chloride excretion was not associated with risk of CAC progression. Restricted cubic spine depicted an inverted J-shaped curve, with a significant reduction in the risk of CAC progression in subjects with high spot urine chloride-to-creatinine ratios., Conclusion: High urinary chloride excretion is associated with decreased risk of CAC progression in patients with nondialysis CKD.

Background: Several studies have reported that depression is prevalent in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD)., Methods: From the Korean National Health Insurance Service database, we selected 67,866 patients with DKD and body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. Weight change over 2 years was categorized into five groups: ≥-10%, &lt;-10% to ≥-5%, &lt;-5% to &lt;5%, ≥5% to &lt;10%, and ≥10%. The occurrence of depression was monitored via the codes of International Statistical Classification of Diseases, 10th revision through the end of 2018., Results: During the 5.24-year follow-up, 17,023 patients with DKD developed depression. Weight change and the risk of depression had a U-shaped relationship: patients with ≥-10% weight change (hazard ratio [HR], 1.12) and those with ≥10% weight change (HR, 1.11) showed higher HRs for depression than those with &lt;-5% to &lt;5% weight change, even after adjusting for several confounding factors. In the subgroup analyses, the risk of depression tended to increase as weight gain or weight loss increased in all subgroups., Conclusion: Both weight loss and weight gain increased the risk of depression in patients with DKD.

Background: Osteoprotegerin is an important regulator of bone metabolism and vascular calcification. The association between serum osteoprotegerin level and chronic kidney disease (CKD) progression has not been elucidated. We investigated the prognostic value of serum osteoprotegerin levels in nondialysis CKD patients., Methods: We analyzed 2,082 patients enrolled in the Korean Cohort Study for Outcomes in Patients with CKD between 2011 and 2016. Patients were divided into quartiles by their serum osteoprotegerin levels. The primary outcome was the occurrence of ≥1 of the following: dialysis initiation, kidney transplantation, a two-fold increase in serum creatinine level from baseline, or a 50% decrease in the estimated glomerular filtration rate (eGFR). Cox proportional hazard regression models were used to investigate the prognostic value of the serum osteoprotegerin level to CKD progression., Results: The median follow-up period was 48.9 months, and 641 patients (30.8%) experienced the primary outcome. The hazard ratio of serum osteoprotegerin for renal progression in the full extended Cox proportional hazard model was 1.064 (95% confidence interval, 1.041-1.088). Subgroup analyses by age, presence of diabetes, and eGFR showed significant results consistent with the overall analysis results., Conclusion: Serum osteoprotegerin level is independently associated with renal prognosis and could have prognostic importance in CKD progression.

Background: Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD., Methods: A total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation., Results: A total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09-1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59-7.31; p < 0.001)., Conclusion: Our study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

Background: Hypertension is the most important modifiable risk factor for mortality and morbidity in chronic kidney disease and coronary artery syndrome. The effect of hypertension prior to percutaneous coronary intervention (PCI) on the development of end-stage renal disease (ESRD) is unknown., Methods: We used nationally representative data from the Korean National Health Insurance System-140,164 subjects were enrolled during 2010-2015; they were free of ESRD at enrolment, underwent PCI, and were followed up until 2017. Blood pressure (BP) was measured within at least 2 years prior to PCI. The primary outcome was the development of ESRD., Results: During a median follow-up of 5.4 years, 2,082 participants (1.5%) developed ESRD. The highest systolic BP group (>160 mmHg) showed a higher hazard ratio (3.69; 95% confidence interval, 2.61-5.23) than the reference group (110-119 mmHg). Similar results were observed in the highest diastolic BP group (>120 mmHg), which showed a higher hazard ratio than the reference group (70-79 mmHg). However, ESRD risk showed a J-shaped relationship with baseline systolic and diastolic BP at 113 and 74 mmHg in diabetes mellitus subgroup, respectively, after adjustment for potential confounders., Conclusion: Our study showed that a high systolic or diastolic BP prior to PCI was independently associated with an increased incidence of ESRD.

Background: Compared to the general population, patients with end-stage renal disease have more gastrointestinal symptoms and a higher prevalence of peptic ulcer. Risk factors for peptic ulcer disease in patients with end-stage renal disease, however, remain poorly defined. This study aims to better identify those risk factors., Methods: We analyzed 577 patients with end-stage renal disease from 2004 to 2016. We excluded patients with life-threatening conditions. All patients underwent upper endoscopy. We analyzed patient medical records, medication history, and endoscopic findings. Independent sample t test, chi-square test, Fisher's exact test, and multiple logistic regression analysis were used in statistical analyses., Results: Of the 577 patients with end-stage renal disease, 174 had peptic ulcer disease (gastric or duodenal ulcer). Patients on hemodialysis had a higher prevalence of peptic ulcer disease than those on peritoneal dialysis. Patients with peptic ulcer disease had lower serum albumin level and higher blood urea nitrogen level than those without peptic ulcer disease. Positive scores on two or more nutritional indices (albumin, serum cholesterol, uric acid, and creatinine levels) were associated with peptic ulcer disease in end-stage renal disease., Conclusion: Hemodialysis, hypoalbuminemia, and multiple malnutrition indices were associated with the prevalence of peptic ulcer disease in patients with end-stage renal disease receiving dialysis.

Background: It is thought that hyperuricemia might lower the risk of mortality among hemodialysis patients, unlike in the general population, but the evidence is controversial. The aim of the current study was to evaluate the impact of serum uric acid level on the long-term clinical outcomes of hemodialysis patients in Korea., Methods: Retrospective analysis was performed on data from the End-Stage Renal Disease Registry of the Korean Society of Nephrology. This included data for 7,333 patients (mean age, 61 ± 14 years; 61% male) who received hemodialysis from January 2001 through April 2015. Initial laboratory data were used in the analysis., Results: The mean serum uric acid level in this study was 7.1 ± 1.7 mg/dL. Body mass index, normalized protein catabolic rate, albumin, and cholesterol were positively correlated with serum uric acid level after controlling for age and sex. After controlling for demographic data, comorbidities, and residual renal function, a higher uric acid level was independently associated with a significantly lower all-cause mortality (hazard ratio [HR], 0.90 per 1 mg/dL increase in uric acid level; 95% confidence interval [CI], 0.83-0.97; P = 0.008), but not cardiovascular mortality (HR, 0.90; 95% CI, 0.80-1.01; P = 0.078). Comparing uric acid levels in the highest and lowest quintiles, the HR for all-cause mortality was 0.65 (95% CI, 0.42-0.99; P = 0.046)., Conclusion: Hyperuricemia was strongly associated with a lower risk of all-cause mortality, but there seems to be no significant association between serum uric acid level and cardiovascular mortality among Korean hemodialysis patients with end-stage renal disease., Competing Interests: Conflicts of interest All authors have no conflicts of interest to declare.

Background: Incident hemodialysis patients have the highest mortality in the first several months after starting dialysis. This study evaluated the in-hospital mortality rate after hemodialysis initiation, as well as related risk factors., Methods: We examined in-hospital mortality and related factors in 2,692 patients starting incident hemodialysis. The study population included patients with acute kidney injury, acute exacerbation of chronic kidney disease, and chronic kidney disease. To determine the parameters associated with in-hospital mortality, patients who died in hospital (nonsurvivors) were compared with those who survived (survivors). Risk factors for in-hospital mortality were determined using logistic regression analysis., Results: Among all patients, 451 (16.8%) died during hospitalization. The highest risk factor for in-hospital mortality was cardiopulmonary resuscitation, followed by pneumonia, arrhythmia, hematologic malignancy, and acute kidney injury after bleeding. Albumin was not a risk factor for in-hospital mortality, whereas C-reactive protein was a risk factor. The use of vancomycin, inotropes, and a ventilator was associated with mortality, whereas elective hemodialysis with chronic kidney disease and statin use were associated with survival. The use of continuous renal replacement therapy was not associated with in-hospital mortality., Conclusion: Incident hemodialysis patients had high in-hospital mortality. Cardiopulmonary resuscitation, infections such as pneumonia, and the use of inotropes and a ventilator was strong risk factors for in-hospital mortality. However, elective hemodialysis for chronic kidney disease was associated with survival.

A 52-year-old man undergoing continuous ambulatory peritoneal dialysis presented with two consecutive episodes of peritonitis caused by unusual organisms, namely, Brevibacterium and Pantoea agglomerans. The patient was successfully treated with a 2-week course of cefazolin and ceftazidime for the Brevibacterium-associated peritonitis, and a 3-week course of gentamicin for the P. agglomerans-associated peritonitis. Although these environmental organisms are rarely responsible for human infection, the number of reported cases of human infection by these unusual organisms has increased. This report emphasizes the potential for infection by environmental organisms in patients undergoing peritoneal dialysis.

We report an unusual case of probable Creutzfeldt-Jakob disease (CJD) in hemodialysis patient. A woman 59 years of age with a past history of hypertension and end-stage renal disease presented with a stuporous state preceded by rapidly progressive cognitive dysfunction, myoclonus, and akinetic mutism. At first, the cause of the altered mental status was assumed to be uremic or hypertensive encephalopathy combined with fever. Proper managements, however, did not improve the neurologic symptoms. Diffusion-weighted magnetic resonance imaging revealed bilaterally asymmetric high signal intensity in both basal ganglia and cerebral cortices. Electroencephalography showed diffuse generalized theta-to-delta range slow wave and intermittent medium-to-high voltage complexes with a characteristic triphasic pattern on both hemispheres. Cerebrospinal fluid assay for the 14-3-3 protein was positive and diagnostic of CJD.