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Background Continuous renal replacement therapy (CRRT) has become the standard modality of renal replacement therapy (RRT) in critically ill patients. However, consensus is lacking regarding the criteria for discontinuing CRRT. Here we validated the usefulness of the prediction model for successful discontinuation of CRRT in a multicenter retrospective cohort. Methods One temporal cohort and four external cohorts included 1,517 patients with acute kidney injury who underwent CRRT for >2 days from 2018 to 2020. The model was composed of four variables: urine output, blood urea nitrogen, serum potassium, and mean arterial pressure. Successful discontinuation of CRRT was defined as the absence of an RRT requirement for 7 days thereafter. Results The area under the receiver operating characteristic curve (AUROC) was 0.74 (95% confidence interval, 0.71–0.76). The probabilities of successful discontinuation were approximately 17%, 35%, and 70% in the low-score, intermediate-score, and high-score groups, respectively. The model performance was good in four cohorts (AUROC, 0.73–0.75) but poor in one cohort (AUROC, 0.56). In one cohort with poor performance, attending physicians primarily controlled CRRT prescription and discontinuation, while in the other four cohorts, nephrologists determined all important steps in CRRT operation, including screening for CRRT discontinuation. Conclusion The overall performance of our prediction model using four simple variables for successful discontinuation of CRRT was good, except for one cohort where nephrologists did not actively engage in CRRT operation. These results suggest the need for active engagement of nephrologists and protocolized management for CRRT discontinuation.

Background Whether advanced age is associated with poor outcomes of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is controversial. This study aimed to evaluate age effect and predictors for mortality in elderly AKI patients undergoing CRRT. Methods Data of 480 elderly AKI patients who underwent CRRT were retrospectively analyzed. Subjects were stratified into two groups according to age: younger-old (age, 65–74 years; n = 205) and older-old (age, ≥75 years; n = 275). Predictors for 28-day and 90-day mortality and age effects were analyzed using multivariable Cox regression analysis and propensity score matching. Results Urine output at the start of CRRT (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.99–1.00; p = 0.04), operation (aHR, 0.53; 95% CI, 0.30–0.93; p = 0.03), and use of an intra-aortic balloon pump (aHR, 3.60; 95% CI, 1.18–10.96; p = 0.02) were predictors for 28-day mortality. Ischemic heart disease (aHR, 1.74; 95% CI, 1.02–2.98; p = 0.04) and use of a ventilator (aHR, 0.56; 95% CI, 0.36–0.89; p = 0.01) were predictors for 90-day mortality. The older-old group did not exhibit a higher risk for 28-day or 90-day mortality than the younger-old group in multivariable or propensity score-matched models. Conclusion Advanced age was not a risk factor for mortality among elderly AKI patients undergoing CRRT, suggesting that advanced age should not be considered for therapeutic decisions in critically ill elderly patients with AKI requiring CRRT.

Background Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. Methods A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. Results Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. Conclusion Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

When sodium-glucose cotransporter-2 (SGLT2) inhibitors were first introduced a decade ago, no one expected them to have substantial effects beyond their known glucose-lowering effects, until the emergence of evidence of their robust renal and cardiovascular benefits showing that they could attenuate progression of kidney disease, irrespective of diabetes, as well as prevent the development of acute kidney injury. Still, the precise and elaborate mechanisms underlying the major organ protection of SGLT2 inhibitors remain unclear. SGLT2 inhibitors inhibit the reabsorption of sodium and glucose in the proximal tubule of the kidney and then recovers tubuloglomerular feedback, whereby SGLT2 inhibitors reduce glomerular hyperfiltration. This simple demonstration of their beneficial effects has perplexed experts in seeking more plausible and as yet undisclosed explanations for the whole effects of SGLT2 inhibitors, including metabolism reprogramming and the modulation of hypoxia, inflammation, and oxidative stress. Given that the renal benefits of SGLT2 inhibitors in patients with kidney disease but without diabetes were comparable to those seen in patients with diabetes, it may be reasonable to keep the emphasis on their hemodynamic actions. In this context, the aim of the present review is to provide a comprehensive overview of renal hemodynamics in individuals with diabetes who are treated with SGLT2 inhibitors, with a focus on natriuresis associated with the regulation of tubuloglomerular feedback and potential aquaresis. Throughout the discussion of alterations in renal sodium and water transports, particular attention will be given to the potential enhancement of adenosine and its receptors following SGLT2 inhibition.

Abstract Fluid overload secondary to loss of functional nephron mass can elevate blood pressure, which is characteristic of hypertension shown in chronic kidney disease (CKD). Therefore, it is logical to use diuretics at appropriate dose to lower blood pressure in patients with CKD and hypertension. Despite the theoretical background on the use of diuretics in CKD, there have been no definitive data on the effectiveness or safety of diuretics as first-line therapy for the management of hypertension in patients with CKD. Results from some clinical trials have demonstrated that diuretics would not lower blood pressure. They could even worsen electrolyte imbalance and kidney function when they are administered in patients with CKD. Major clinical practice guidelines on management of blood pressure or CKD have stated that evidence for benefits of thiazide diuretics is not conclusive yet in patients with advanced CKD, although loop diuretics are often effective for volume control at lower glomerular filtration rate. Recently, evidence for diuretics as effective blood pressure lowering agents in patients with advanced CKD is increasing. Renoprotective effect of thiazide or loop diuretics might represent a consequence of their influence on blood pressure or their ability to potentiate the effect of renin-angiotensin system blockade by making intraglomerular pressure more renin-angiotensin system-dependent, although their direct benefit on renal function remains controversial. This review summarizes recent data on the possible role of diuretics in lowering blood pressure, slowing the progression of kidney disease, and reducing cardiovascular risk in CKD patients.

Background/Aims Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy. Methods Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later. Results We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08). Conclusions Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.

Background Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. Methods Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. Results Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. Conclusion These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.

Abstract Few studies have investigated the impact of a change in metabolic syndrome (MetS) components on clinical renal outcomes in the general population. Using nationally representative data from the Korean National Health Insurance System, 13,310,924 subjects who underwent two health examinations over 2 years and were free from end-stage renal disease (ESRD) from 2009 to 2012 were followed to the end of 2016. The subjects were divided into four groups according to the change in MetS components between the two visits over 2 years: no MetS (–/–), post-MetS (–/+), pre-MetS (+/–), and both MetS (+/+). After a median follow up of 5.11 years, 18,582 incident ESRD cases were identified. In the multivariate adjusted model, the hazard ratio (HR) and 95% confidence interval (CI) for the development of ESRD in the both-MetS (+/+) group compared with the no-MetS (–/–) group was 5.65 (95% CI, 5.42–5.89), which was independent of age, sex, and baseline estimated glomerular filtration rate. Additionally, the HR for the pre-MetS (+/–) group versus the no-MetS (–/–) group was 2.28 (2.15–2.42). In subgroup analysis according to renal function, the impact of a change in MetS on the incidence of ESRD was more pronounced in individuals with advanced renal dysfunction. Subjects with resolved MetS components had a decreased risk of ESRD, but not as low as those that never had MetS components. This provides evidence supporting the strategy of modulating MetS in the general population to prevent the development of ESRD.

Objective: Although short adult height has been associated with an increasing variety of diseases and all-cause death, no reliable data exist on the association between adult height and end-stage renal disease (ESRD) in diabetic patients. We investigated the relationship between short adult height, development of ESRD, and mortality in type 2 diabetes mellitus (DM). Methods: This nationwide population-based cohort study analyzed clinical data from a total of 2,621,907 subjects aged ≥30 years with type 2 DM between January 1, 2009 and December 31, 2012, using the National Health Insurance Database in Korea. Results: During a 6.9-year follow-up period, 220,457 subjects (8.4%) died, and 28,704 subjects (1.1%) started dialysis. Short adult height significant ly increased the incidence of ESRD and all-cause mortality in the overall cohort analysis. In multivariable Cox models, hazard ratios (HR) for the development of ESRD comparing the highest and lowest quartiles of adult height were 0.86 (95% CI 0.83–0.89). All-cause mortality also decreased with the highest height compared to patients with the lowest height, after fully adjusting for confounding variables (HR 0.79, 95% CI 0.78–0.81). Adult height had an inverse relationship to newly diagnosed ESRD (male: HR 0.86, 95% CI 0.83–0.90, female: HR 0.84, 95% CI 0.79–0.90) and all-cause mortality (male: HR 0.81, 95% CI 0.79–0.82, female: HR 0.80, 95% CI 0.78–0.82). Conclusions: Short adult height is strongly associated with the increased risk of ESRD development and all-cause mortality in type 2 DM.

Abstract Background Because weight control is a cornerstone of diabetes management, it is important to understand the relationship of weight change to risk of cardiovascular disease (CVD) among patients with type 2 diabetes mellitus (DM). We aimed to investigate whether changes in weight early after diagnosis influence the incidence of CVD and all-cause mortality in patients with type 2 DM. Methods Using nationally representative data from the Korean National Health Insurance System, 173,246 subjects with new-onset DM who underwent health examinations during 2007–2012 were included. Weight was measured at the time of diabetes diagnosis and 2 years later. Weight change over 2 years was divided into five categories of 5% weight change, from weight loss ≥ − 10% to weight gain ≥ 10%. Results There were 3113 deaths (1.8%), 2060 cases of stroke (1.2%), and 1767 myocardial infarctions (MIs) (1.0%) during a median follow-up of 5.5 years. Subjects with weight gain ≥ 10% had a significantly higher risk of stroke (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.23–1.84), compared with the group with stable weight. There was no significant association between weight change after diagnosis of DM and incident MI. All-cause mortality showed a U-shaped curve according to weight change. The group with weight loss ≥ − 10% had the highest HR for all-cause mortality (HR 1.86; 95% CI 1.61–2.14) and the HR for weight gain ≥ 10% was 1.61 (95% CI 1.37–1.89). Conclusions Weight changes of more than 10% after diabetes diagnosis were associated with higher mortality and over 10% weight gain was associated with increased risk of stroke.

Besides lowering glucose, empagliflozin, a selective sodium-glucose cotransporter-2 (SGLT2) inhibitor, have been known to provide cardiovascular and renal protection due to effects on diuresis and natriuresis. However, the natriuretic effect of SGLT2 inhibitors has been reported to be transient, and long-term data related to diuretic change are sparse. This study was performed to assess the renal effects of a 12-week treatment with empagliflozin (3 mg/kg) in diabetic OLETF rats by comparing it with other antihyperglycemic agents including lixisenatide (10 μg/kg), a glucagon-like peptide receptor-1 agonist, and voglibose (0.6 mg/kg), an α-glucosidase inhibitor. At 12 weeks of treatment, empagliflozin-treated diabetic rats produced still high urine volume and glycosuria, and showed significantly higher electrolyte-free water clearance than lixisenatide or voglibose-treated diabetic rats without significant change of serum sodium level and fractional excretion of sodium. In empagliflozin-treated rats, renal expression of Na+-Cl- cotransporter was unaltered, and expressions of Na+/H+ exchanger isoform 3, Na+-K+-2Cl- cotransporter, and epithelial Na+ channel were decreased compared with control diabetic rats. Empagliflozin increased an expression of aquaporin (AQP)7 but did not affect AQP3 and AQP1 protein expressions in diabetic kidneys. Despite the increased expression in vasopressin V2 receptor, protein and mRNA levels of AQP2 in empagliflozin-treated diabetic kidneys were significantly decreased compared to control diabetic kidneys. In addition, empagliflozin resulted in the increased phosphorylation of AQP2 at S261 through the increased cyclin-dependent kinases 1 and 5 and protein phosphatase 2B. These results suggest that empagliflozin may contribute in part to polyuria via its regulation of sodium channels and AQP2 in diabetic kidneys.

BackgroundThe aim of this study was to investigate the changes of body composition and muscle strength of North Korean refugees (NKRs) according to their duration of stay in South Korea.MethodsNKRs who volunteered and were living in South Korea, aged 20 to 75 years were recruited. Body compositions were analyzed by bioelectrical impedance analysis. Muscle strength was measured with the hand grip test. Demographic and migration information was obtained with a questionnaire.ResultsA total of 158 volunteers were recruited at a mean age of 48.3±11.4 years. The mean time from when they escaped from North Korea and arrived in South Korea was 5.8±4.3 years. Height, weight, and body surface area were significantly smaller in all NKRs compared to South Korean controls, except for women aged over 50 years. In females of younger ages (

[This corrects the article DOI: 10.1371/journal.pone.0181757.].

The aim of this study was to assess any potential additive effects of a treatment combining aliskiren with paricalcitol on reducing renal fibrosis. C57BL/6J mice were treated individually with aliskiren and/or paricalcitol until 7 days after initiation of unilateral ureteral obstruction (UUO).In obstructed kidneys of UUO mice, monotherapy with aliskiren or paricalcitol significantly attenuated interstitial fibrosis, collagen IV accumulation, and α-smooth muscle actin- and terminal deoxynucleotidyl transferase-mediated biotin nick end-labeling-positive cells. The combination treatment showed additive efficacy in inhibition of these parameters. Renal NADPH oxidase (Nox)1 and Nox2 were significantly decreased by aliskiren or paricalcitol alone or in combination, while renal Nox4 expression was significantly reduced by paricalcitol mono- or combination treatment. Increased levels of p-Erk and p-p38 MAPK, and NF-κB in UUO kidneys were also significantly reduced by either aliskiren or paricalcitol treatment alone or in combination. Aliskiren or paricalcitol monotherapy significantly reduced the expression of (pro)renin receptor in UUO kidneys. In addition, aliskiren tended to augment renin expression in UUO kidneys, but paricalcitol reduced its expression level. The combination treatment effectively blocked both (pro)renin receptor and renin expression induced by aliskiren, and resulted in a further reduction of the renal expression of angiotensin II AT1 receptor. Aliskiren failed to increase the expression of vitamin D receptor in UUO kidneys, but the combination treatment restored its expression level. Taken together, a treatment combining aliskiren with paricalcitol better inhibits UUO-induced renal injury. The mechanism of this synergy may involve more profound inhibition of the intrarenal renin-angiotensin system.

Gamma-glutamyltransferase (GGT) is a biomarker of liver injury. GGT has also been reported to be a marker of oxidative stress and a predictor of mortality in the general population. Hemodialysis (HD) patients suffer from oxidative stress. The aim of our study was to investigate the relationship between serum GGT levels and clinical outcomes in HD patients.A total of 1,634 HD patients were enrolled from the Clinical Research Center registry for end-stage renal disease, a prospective cohort in Korea. Patients were categorized into three groups by tertiles of serum GGT levels. The primary outcome was all-cause, cardiovascular, or infection-related mortality and hospitalization.During the median follow-up period of 30 months, the highest tertile of serum GGT levels had a significantly higher risk for all-cause mortality (hazard ratio (HR) 2.39, 95% confidence interval (CI), 1.55-3.69, P

Acute kidney injury (AKI) is characterized by an abrupt decline of excretory kidney function. The incidence of AKI has increased in the past decades. Patients diagnosed with AKI often undergo diverse clinical trajectories, such as early or late recovery, relapses, and even a potential transition from AKI to chronic kidney disease (CKD). Although recent clinical studies have demonstrated a strong association between AKI and progression of CKD, our understanding of the complex relationship between AKI and CKD is still evolving. No cohort study has succeeded in painting a comprehensive picture of these multi-faceted pathways. To address this lack of understanding, the idea of acute kidney disease (AKD) has recently been proposed. This presents a new perspective to pinpoint a period of heightened vulnerability following AKI, during which a patient could witness a substantial decline in glomerular filtration rate, ultimately leading to CKD transition. Although AKI is included in a range of kidney conditions collectively known as AKD, spanning from mild and self-limiting to severe and persistent, AKD can also occur without a rapid onset usually seen in AKI, such as when kidney dysfunction slowly evolves. In the present review, we summarize the most recent findings about AKD, explore the current state of biomarker discovery related to AKD, discuss the latest insights into pathophysiological underpinnings of AKI to CKD transition, and reflect on therapeutic challenges and opportunities that lie ahead. [ABSTRACT FROM AUTHOR]

Objective: Obesity and type 2 diabetes are becoming increasingly prevalent worldwide and are both associated with the increased incidence of kidney and bladder cancers. However, previous reports have provided conflicting results. We investigated the impact of body mass index (BMI) and diabetes on the incidence of both cancers in the general population. Methods: Using nationally representative data from the Korean National Health Insurance System, 9,777,133 subjects without any malignancy who underwent health examinations in 2009 were followed to the end of 2017. Results: After a median follow-up period of 8.32 years, 12,544 incidents of kidney cancer and 15,137 incidents of bladder cancer were identified. The hazard ratio (HR) for kidney cancer was the lowest in people with a BMI <18.5 kg/m² (HR: 0.82, 95% confidence interval (CI): 0.72-0.94) and the highest in those with a BMI ≥30 kg/m² (HR: 1.71, 95% CI: 1.57-1.87) compared to a reference BMI group (18.5-23 kg/m²). In subjects with diabetes, obesity was associated with increased risk of kidney cancer, although the HRs were lower than observed in those without diabetes. Otherwise, there was a reduction in risk of bladder cancer with obesity in men and the HR for bladder cancer was not affected by BMI increase in women. There was a strongly positive association between diabetes and bladder cancer in the total study population. Conclusions: Obesity was a strong risk factors for kidney cancer, whereas the association between obesity and bladder cancer differed by gender. The subjects with diabetes had a higher risk for both cancers than those without diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study examined the association between baseline BMI, percentage weight change, and the risk of dementia in patients newly diagnosed with type 2 diabetes.Research Design and Methods: Using the South Korean National Health Insurance Service-National Health Screening Cohort database, we identified 167,876 subjects aged ≥40 years diagnosed with new-onset type 2 diabetes between 2007 and 2012. Their weight changes were monitored for ∼2 years after diagnosis, with follow-up assessments occurring for an average of 3.5 years. The hazard ratios (HRs) and Bonferroni-adjusted 95% CIs of all-cause dementia, Alzheimer disease (AD), and vascular dementia were estimated using multivariable Cox proportional hazards regression models.Results: We identified 2,563 incident dementia cases during follow-up. Baseline BMI among patients with new-onset type 2 diabetes was inversely associated with the risk of all-cause dementia and AD, independent of confounding variables (P for trend <0.001). The percentage weight change during the 2 years after a diagnosis of type 2 diabetes showed significant U-shaped associations with the risk of all-cause dementia development (P < 0.001); the HRs of the disease increased significantly when weight loss or gain was >10% (1.34 [95% CI 1.11-1.63] and 1.38 [1.08-1.76], respectively). Additionally, weight loss >10% was associated with an increased risk of AD (HR 1.26 [95% CI 1.01-1.59]).Conclusions: A lower baseline BMI was associated with increased risks of all-cause dementia and AD in patients with new-onset type 2 diabetes. Weight loss or weight gain after the diagnosis of diabetes was associated with an increased risk of all-cause dementia. Weight loss was associated with an increased risk of AD. [ABSTRACT FROM AUTHOR]

Blood manganese (Mn) level has been reported to be higher in patients with anemia or iron deficiency. The purpose of this study was to analyze the relationship between blood Mn level and anemia in patients with chronic kidney disease (CKD). A total of 334 patients with CKD who were not treated with dialysis were included in this study. Blood Mn level and serum markers regarding anemia, renal function, and nutrition were measured and analyzed. Median blood Mn level was 8.30 (interquartile range(IQR): 5.27-11.63) μg/L. Univariate linear regression showed that blood Mn level was correlated with age (β = -0.049, p < 0.001), smoking (β = -1.588, p = 0.009), hypertension (β = -1.470, p = 0.006), serum total iron-binding capacity (TIBC) (β = 0.025, p < 0.001), serum transferrin (β = 0.029, p < 0.001), and estimated glomerular filtration rate (eGFR; β = 0.036, p < 0.001). Results of multiple linear regression analysis showed that beta coefficient of hemoglobin was 0.847 (p < 0.001) for blood Mn level in all participants after controlling for covariates, including gender, age, body mass index, smoking, diabetes, hypertension, and eGFR. Multivariate Poisson regression analysis with robust variance after adjusting for gender, age, smoking, hypertension, diabetes, eGFR, and nutritional markers showed that higher blood Mn level (per 1 μg/L increase) was associated with decreased prevalence of anemia (PR 0.974, 95% CI: 0.957 to 0.992, p = 0.005). Taken together, our results demonstrate that blood Mn level is positively associated with hemoglobin level in CKD patients. This might provide important information in the understanding of the pathogenesis of CKD-related anemia. [ABSTRACT FROM AUTHOR]

Background: Fabry disease is a rare X-linked lysosomal storage disorder caused by α-galactosidase A deficiency. With the advancement of molecular diagnostic tools, more disease-causing mutations in α-galactosidase A (GLA) have been identified in Fabry disease. We found a novel mutation in a Korean family with predominant renal manifestations of the disease. Case presentation: A 24-year-old man who wanted to donate a kidney to his 28-year-old brother with end-stage renal disease of unknown cause was evaluated. The 24-year-old man underwent percutaneous renal biopsy because of an accidentally found proteinuria. Electron microscopy of his renal biopsy showed numerous electron-dense multilamellar inclusions in the epithelial cytoplasm, typical for Fabry disease. Clinical and laboratory evaluation including the assessment of GLA enzyme activity and direct DNA sequencing in four members of the family were performed. Renal biopsy findings in the two affected male patients were described. Re-evaluation of a renal biopsy specimen of his 28-year-old brother obtained when he was diagnosed with renal failure revealed a very focal area of suspicious multilamellated structures in the Bowman’s space. DNA sequencing on the young man, his brother, and his mother revealed a novel GLA gene mutation, c.263A > G (p.Tyr88Cys). The three all showed decreased α-galactosidase A activity. Conclusion: A novel GLA mutation, c.263A > G (p.Tyr88Cys), was found in a Korean family with predominant renal manifestations of Fabry disease. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the changes of body composition and muscle strength of North Korean refugees (NKRs) according to their duration of stay in South Korea. Methods: NKRs who volunteered and were living in South Korea, aged 20 to 75 years were recruited. Body compositions were analyzed by bioelectrical impedance analysis. Muscle strength was measured with the hand grip test. Demographic and migration information was obtained with a questionnaire. Results: A total of 158 volunteers were recruited at a mean age of 48.3 ± 11.4 years. The mean time from when they escaped from North Korea and arrived in South Korea was 5.8±4.3 years. Height, weight, and body surface area were significantly smaller in all NKRs compared to South Korean controls, except for women aged over 50 years. In females of younger ages (<50 years), NKRs with more than a 4-year stay in South Korea had a higher weight and fat mass than that of those who had a shorter stay (less than 4 years) in South Korea. All NKRs had a weaker grip strength than that of the age-matched controls from South Korea. Conclusion: The NKRs showed relatively smaller physiques and weaker muscle strength than that of the South Korean controls. In younger female NKRs, shorter South Korean stay group showed small body weight and fat mass than that of longer South Korean stay group. Specific health support programs might be needed. [ABSTRACT FROM AUTHOR]

Background: Anthocyanins are major constituents of food colours and have been reported to possess anti-diabetic activities for potential medicinal use. The precise role of anthocyanins in diabetic nephropathy is poorly understood. We investigated whether anthocyanin-rich Seoritae extract (SE) can potentially prevent oxidative stress and lipotoxicity, which are the main causes of renal damage in diabetic nephropathy, via activation of AMP-activated protein kinase (AMPK) and the consequent effects on its target molecules. Methods: Four groups of male C57BLKS/J db/m and db/db mice were used. Diabetic and non-diabetic mice were orally administered 10 mg/kg body weight SE daily for 12 weeks, starting at 8 weeks of age. Results: db/db mice treated with anthocyanins showed decreased albuminuria. Anthocyanins ameliorated intrarenal lipid concentrations in db/db mice with improvement of glomerular matrix expansion and inflammation, which was related to increased phosphorylation of AMPK and activation of peroxisome proliferator-activated receptor (PPAR) α and PPARγ, and inhibited the activity of acetyl-CoA carboxylase and sterol regulatory element-binding protein 1. Anthocyanins reversed diabetes-induced increases in renal apoptosis and oxidative stress. In cultured human glomerular endothelial cells, anthocyanins prevented high glucose-induced oxidative stress and apoptosis through activation of AMPK in the same manner. Conclusions: The results revealed that anthocyanins ameliorated diabetic nephropathy in db/db mice via phosphorylation of AMPK, the major energy-sensing enzyme, and the consequent effects on its target molecules, which appeared to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney. [ABSTRACT FROM AUTHOR]

Purpose To investigate age and gender patterns in associations between lifestyle factors and physical performance in community-dwelling older Korean adults. Design and methods A cross-sectional study was conducted in a population-based sample of an urban area. Randomly sampled older Korean adults (n = 664; mean age, 74.6 years) participated. Data on current physical activity level and doing exercise, social participation and hobbies, smoking status, drinking status, sleep quality, and physical performance were obtained. Binary logistic regression analyses were used to identify the age and gender patterns in associations between various lifestyle factors and physical performance. Results In younger (age <85 years) men, significant predictors of poor physical performance by logistic regression analysis after adjusting for covariates were current physical activity time, doing exercise, and engagement in social activities. In younger women, current physical activity time and sleep quality were related to poor physical performance. In older (age ≥85 years) men, family gatherings were a significant factor. In older women, no lifestyle factor assessed showed a significant relationship with poor physical performance. Conclusion Interventions implemented to modify lifestyle factors need to focus on age and gender subgroups in the elderly population. Lifestyle modification should be emphasised as a targeted treatment program for Korean adults aged <85 years. [ABSTRACT FROM AUTHOR]

Background Although percutaneous renal biopsy remains an essential tool in the diagnosis and treatment of renal diseases, in recent times the traditional procedure of nephrologists have been performed by non-nephrologists rather than nephrologists at many institutions. The present study assessed the safety and adequacy of tissue yield during percutaneous renal biopsy according to practitioners and techniques based on ultrasound. Methods This study included 658 native renal biopsies performed from 2005 to 2010 at a single centre. The biopsies were performed by nephrologists or expert ultrasound radiologists using the ultrasound-marked blind or real-time ultrasound-guided techniques. Results A total of 271 ultrasound-marked blind biopsies were performed by nephrologists, 170 realtime ultrasound-guided biopsies were performed by nephrologists, and 217 real-time ultrasound-guided biopsies were performed by radiologists during the study period. No differences in post-biopsy complications such as haematoma, need for transfusion and intervention, gross haematuria, pain, or infection were observed among groups. Glomerular numbers of renal specimens from biopsies performed by nephrologists without reference to any technique were higher than those obtained from real-time ultrasound-guided biopsies performed by expert ultrasound radiologists. Conclusions Percutaneous renal biopsy performed by nephrologists was not inferior to that performed by expert ultrasound radiologists as related to specimen yield and post-biopsy complications. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate the association between blood manganese levels and the prevalence of chronic diseases in the Korean population. Methods This was a cross-sectional study based on the Korean National Health and Nutrition Examination Survey (KNAHNES). The study included 3996 participants 20 years of age or older whose blood manganese levels had been measured. The participants were also evaluated for the presence of five chronic diseases: diabetes, renal dysfunction, hypertension, ischemic heart disease, and stroke. Results Blood manganese levels were significantly lower in the diabetes group compared with the non-diabetes group (1.26 ± 0.02 vs. 1.35 ± 0.01 μg/dL; p = 0.001) and the renal dysfunction group compared with those with normal renal function (1.28 ± 0.03 vs. 1.35 ± 0.01 μg/dL; p = 0.04). There was no significant association between blood manganese levels and the presence of ischemic heart disease or stroke. A multivariate logistic regression analysis adjusted for age, sex, and body mass index was performed; the odds ratio was 0.652 (95% CI: 0.46-0.92) for diabetes and 0.589 (95% CI: 0.39-0.88) for renal dysfunction when comparing the higher quartiles (Q2-4) with the lowest quartile (Q1) of blood manganese level. The prevalence of diabetes was 7.6% in Q1 and 5.3% in Q2-4 (p = 0.02). Similarly, the prevalence of renal dysfunction was 6.8% in Q1, compared with 4.6% in Q2-4 (p = 0.02). Conclusion The prevalence of diabetes and renal dysfunction increased in participants with low blood manganese levels, suggesting that blood manganese may play a role in glucose homeostasis and renal function. [ABSTRACT FROM AUTHOR]

Background Nuclear factor erythroid-2-related factor-2 (Nrf2) is known to protect against tissue injury by orchestrating antioxidant and detoxification responses to oxidative stress. This study investigated whether upregulation of Nrf2-dependent signaling by oleanolic acid (OA), which is known to activate Nrf2, could attenuate renal inflammation and fibrosis in cyclosporine (CsA)-induced kidney injury. Methods Male ICR mice were divided into four treatment groups: Vehicle (VH, n = 6), VH + OA (n = 6), CsA (n = 8), and CsA + OA (n = 8). For the OA-treated groups, OA (25 mg/kg/day) was administered by intraperitoneal injection for the final week of the 4-week experimental period. Renal function, morphologies and signaling were evaluated at the end of the study. Results Treatment with CsA resulted in decreased kidney function and urine osmolality and increased urine volume and urinary albumin levels. The CsA-induced changes were improved by OA treatment. Specifically, administration of OA decreased tubulointerstitial fibrosis and inflammation scores that were increased in CsA-treated mice. Furthermore, OA treatment decreased urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epiprostaglandin F2α (8- iso-PGF2α) levels. The beneficial effects of OA were attributed to an increased ratio of nuclear/total Nrf2 and subsequently enhanced expression of heme oxygenase (HO)-1, as well as a stable level of Kelch-like ECH-associated protein 1 (Keap1) expression, indicating that OA enhanced nuclear translocation of Nrf2. Increased apoptotic cell death and a high ratio of B cell leukaemia/lymphoma 2 (Bcl-2)-associated X protein (Bax) to Bcl-2 in CsA-treated mice were also significantly ameliorated by OA treatment. Conclusion Our results suggest that OA activates Nrf2/HO-1 signaling in chronic CsA nephropathy, which may have beneficial effects on inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Background Renal interstitial fibrosis is a common final pathological process in the progression of kidney disease. This is primarily due to oxidative stress, which contributes to renal inflammation and fibrosis. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is known to coordinate induction of genes that encode antioxidant enzymes. We investigated the effects of oleanolic acid, a known Nrf2 activator, on oxidative stress-induced renal inflammation and fibrosis. Methods One day before unilateral ureteral obstruction (UUO) performed in C57BL/6 mice, oleanolic acid treatment was initiated and was continued until 3 and 7 days after UUO. Renal inflammation and fibrosis, markers of oxidative stress, and changes in Nrf2 expression were subsequently evaluated. Results In the obstructed kidneys of UUO mice, oleanolic acid significantly attenuated UUO-induced collagen deposition and fibrosis on day 7. Additionally, significantly less inflammatory cell infiltration, a lower ratio of Bax to Bcl-2 expression, and fewer apoptotic cells on TUNEL staining were observed in the obstructed kidneys of oleanolic acid-treated mice. Oleanolic acid increased the expression of nuclear Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and heat shock protein 70, and decreased lipid peroxidation in the obstructed kidney of UUO mice. There were no changes in the expression of total Nrf2 and Kelch-like ECH-associated protein 1, indicating that oleanolic acid enhanced nuclear translocation of Nrf2. Conclusions These results suggest that oleanolic acid may exert beneficial effects on renal fibrosis by increasing nuclear translocation of Nrf2 and subsequently reducing renal oxidative stress. [ABSTRACT FROM AUTHOR]

Renal artery pseudoaneurysm (RAP) is an uncommon but potentially life-threatening condition that is often difficult to diagnose. Rarely, it can occur as a complication associated with a percutaneous renal biopsy procedure. The clinical manifestations vary from asymptomatic lesions found incidentally on imaging studies to a mass causing high blood pressure, pain, haematuria and rupture. Although the risk of rupture is considered low, RAP is associated with a high death rate if ruptured. Currently, with the aid of high-quality interventional radiology, this challenging pathology can be effectively treated. In this report, we describe a case of RAP that was incidentally discovered 4 years after percutaneous renal biopsy which was successfully treated with selective angiographic embolisation. [ABSTRACT FROM AUTHOR]

The differential diagnosis of hypercalcaemia in patients with end-stage renal disease undergoing dialysis should be considered for causes related or unrelated to renal failure itself or therapies for renal failure. In particular, peritoneal dialysis may hinder awareness of a clinical problem due to its own peculiarities and effects on homeostasis of the body, thus creating misconceptions in interpreting laboratory data and diagnosing a disease. We describe here a case of systemic sarcoidosis which was delayed due to failure to recognise underestimated hypercalcaemia in a patient undergoing peritoneal dialysis. Clinicians need to remain aware of the change of minerals that may arise from peritoneal dialysis and should perform an extensive investigation for the cause of hypercalcaemia. [ABSTRACT FROM AUTHOR]

Autophagy is a cellular process that degrades damaged cytoplasmic components and regulates cell death. The homeostasis of endothelial cells (ECs) is crucial for the preservation of glomerular structure and function in aging. Here, we investigated the precise mechanisms of endothelial autophagy in renal aging. The genetic deletion of Atg7 in the ECs of Atg7flox/flox;Tie2-Cre mice accelerated aging-related glomerulopathy and tubulointerstitial fibrosis. The EC-specific Atg7 deletion in aging mice induced the detachment of EC with the disruption of glomerular basement membrane (GBM) assembly and increased podocyte loss resulting in microalbuminuria. A Transwell co-culture system of ECs and kidney organoids showed that the iron and oxidative stress induce the disruption of the endothelial barrier and increase vascular permeability, which was accelerated by the inhibition of autophagy. This resulted in the leakage of iron through the endothelial barrier into kidney organoids and increased oxidative stress, which led to ferroptotic cell death. The ferritin accumulation was increased in the kidneys of the EC-specific Atg7-deficient aging mice and upregulated the NLRP3 inflammasome signaling pathway. The pharmacologic inhibition of ferroptosis with liproxstatin-1 recovered the disrupted endothelial barrier and reversed the decreased expression of GPX4, as well as NLRP3 and IL-1β, in endothelial autophagy-deficient aged mice, which attenuated aging-related renal injury including the apoptosis of renal cells, abnormal structures of GBM, and tubulointerstitial fibrosis. Our data showed that endothelial autophagy is essential for the maintenance of the endothelial barrier during renal aging and the impairment of endothelial autophagy accelerates renal senescence by ferroptosis and NLRP3 inflammasome signaling pathways. These processes may be attractive therapeutic targets to reduce cellular injury from renal aging.

Abstract Objectives To explore the possibility of kidney organoids generated using patient derived human induced pluripotent stem cells (hiPSC) for modeling of Fabry disease nephropathy (FDN). Methods First, we generated hiPSC line using peripheral blood mononuclear cells (PBMCs) from two male FD-patients with different types of GLA mutation: a classic type mutation (CMC-Fb-001) and a non-classic type (CMC-Fb-003) mutation. Second, we generated kidney organoids using wild-type (WT) hiPSC (WTC-11) and mutant hiPSCs (CMC-Fb-001 and CMC-Fb-003). We then compared alpha-galactosidase A (α-GalA) activity, deposition of globotriaosylceremide (Gb-3), and zebra body formation under electromicroscopy (EM). Results Both FD patients derived hiPSCs had the same mutations as those detected in PBMCs of patients, showing typical pluripotency markers, normal karyotyping, and successful tri-lineage differentiation. Kidney organoids generated using WT-hiPSC and both FD patients derived hiPSCs expressed typical nephron markers without structural deformity. Activity of α-GalA was decreased and deposition of Gb-3 was increased in FD patients derived hiPSCs and kidney organoids in comparison with WT, with such changes being far more significant in CMC-Fb-001 than in CMC-Fb-003. In EM finding, multi-lammelated inclusion body was detected in both CMC-Fb-001 and CMC-Fb-003 kidney organoids, but not in WT. Conclusions Kidney organoids generated using hiPSCs from male FD patients might recapitulate the disease phenotype and represent the severity of FD according to the GLA mutation type.

Background: Anemia and iron deficiency are universal problems in patients with chronic kidney disease (CKD). However, decisive indicator to guide the further gastrointestinal (GI) workup has not been determined.Methods: We included 104 anemic patients with nondialysis-dependent CKD stages 3-5 (38 patients at stage 3, 26 patients at stage 4, and 40 patients at stage 5). Hemoglobin, serum ferritin, transferrin saturation (TSAT), mean corpuscular volume (MCV), and corrected reticulocyte count data were assessed to evaluate diagnostic utility for bleeding-related GI lesions, which were identified by esophagogastroduodenoscopy and colonoscopy.Results: Bleeding-related GI lesions were found in 55 (52.9%) patients, and patients with stage 5 CKD had a higher prevalence of gastric lesions than patients with CKD stage 3 or 4 (all p < 0.05). The areas under the receiver operating characteristic curves used to predict bleeding-related lesions were 0.69 for TSAT (p = 0.002) and 0.61 for serum ferritin (p = 0.085). The sensitivity and specificity of a cutoff value for TSAT < 20% were 0.59 and 0.74, respectively. Hemoglobin, MCV, and corrected reticulocyte levels had no significant diagnostic utility. On multivariable logistic regression, the chance of GI lesions increased by 6% for each 1% reduction in TSAT and increased 4.1-fold for patients with CKD stage 5 (all p < 0.05).Conclusions: TSAT is a useful indicator for determining the GI workup in anemic patients with nondialysis-dependent CKD stages 3-5. Stage 5 CKD is independently associated with bleeding-related lesions and TSAT should be used cautiously in these patients.