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Background Bone mineral density (BMD) predicts fracture risk in patients with chronic kidney disease (CKD) and in the general population. However, few studies have investigated risk factors for bone loss in patients with CKD. The aim of this study was to investigate whether renal function is associated with the rate of BMD decline. Methods A prospective cohort study included 1006 patients with CKD stages 2–4 between 2011 and 2016. BMD was measured using dual-energy X-ray absorptiometry at baseline and 4 years. The eGFR was measured 2–6 times during the 4-year follow-up. We analyzed the decline in bone mineral density according to CKD stage and further compared the rate of BMD decline according to eGFR trajectories at each stage. Results Advanced CKD stage was associated with a faster rate of decline in total hip BMD [stage 2 −0.23, stage 3A −0.39, stage 3B −0.80, stage 4 −1.23% change/year in men (P < .001); stage 2 −0.86, stage 3A −1.19, stage 3B −1.20, stage 4 −1.58% change/year in women (P  < .03)]. Two distinct eGFR trajectories (Class 1 stable group; Class 2 rapid decline group) were observed. The rapid decline group showed a trend toward an increased rate of decline in total hip BMD. Subgroup analysis according to eGFR trajectories revealed a significant difference in BMD decline rate between stable and rapid decline groups. Conclusions Advanced CKD stage and accelerated decline in renal function were associated with rapid BMD decline in non-dialysis patients with CKD. [ABSTRACT FROM AUTHOR]

Optimal strategy for volume control and the clinical implication of achieved volume control are unknown in patients with sepsis-associated acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). This randomized controlled trial aimed to compare the survival according to conventional or bioelectrical impedance analysis (BIA)-guided volume control strategy in patients with sepsis-associated AKI receiving CRRT. We also compared patient survival according to achieved volume accumulation rate ([cumulative fluid balance during 3 days × 100]/fluid overload measured by BIA at enrollment) as a post-hoc analysis. We randomly assigned patients to conventional volume control strategy (n = 39) or to BIA-guided volume control strategy (n = 34). There were no differences in 28-day mortality (HR, 1.19; 95% CI, 0.63–2.23) or 90-day mortality (HR, 0.99; 95% CI 0.57–1.75) between conventional and BIA-guided volume control group. In the secondary analysis, achieved volume accumulation rate was significantly associated with patient survival. Compared with the achieved volume accumulation rate of ≤ − 50%, the HRs (95% CIs) for the risk of 90-day mortality were 1.21 (0.29–5.01), 0.55 (0.12–2.48), and 7.18 (1.58–32.51) in that of − 50–0%, 1–50%, and > 50%, respectively. Hence, BIA-guided volume control in patients with sepsis-associated AKI receiving CRRT did not improve patient outcomes. In the secondary analysis, achieved volume accumulation rate was associated with patient survival. [ABSTRACT FROM AUTHOR]

Background: The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes. Methods: The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow‐up period. Results: Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person‐years of follow‐up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person‐years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause‐specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60–0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13–1.64) for BP above both targets, compared with BP controlled within 2012 target only. Conclusion: The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline. [ABSTRACT FROM AUTHOR]

Background: Elevated blood pressure and intrarenal renin-angiotensin system activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between blood pressure and intrarenal renin-angiotensin system activity on the risk of CKD progression is unknown. Methods: We analyzed 2076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic blood pressure (SBP). The urinary angiotensinogen-to-creatinine ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy. Results: During 10 550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and urinary angiotensinogen-to-creatinine ratio on the risk of the primary outcome (P value for interaction=0.019). In patients with urinary angiotensinogen-to-creatinine <3.65 μg/gCr, the hazard ratios (95% CIs) for SBP 120 to 129, 130 to 139, and ≥140 mmHg were 1.46 (1.07–1.99), 1.71 (1.25–2.35), and 2.40 (1.73–3.32), respectively, compared with SBP <120 mmHg. However, these associations were not observed in patients with urinary angiotensinogen-to-creatinine ≥3.65 μg/gCr. Conclusions: In this prospective CKD cohort, higher SBP was associated with CKD progression when urinary angiotensinogen levels were low, while this association was not seen when urinary angiotensinogen levels were high. This finding suggests that intrarenal renin-angiotensin system activity may modify the relationship between SBP and adverse kidney outcome. [ABSTRACT FROM AUTHOR]

Thermal sensitivity of anthocyanin and low‐water solubility of rutin limit their stability in processed foods and biological activity, respectively. Therefore, we aimed to develop a value‐added food composite (VAFC) by mixing of anthocyanin‐enriched potato (P) and rutin‐enriched buckwheat (B) flour using soy lecithin (LCT) and vitamin E (Vita E) by hot‐melt extrusion (HME). The VAFC was formulated using P 50% + B 50% (F1), P 45%+B 45%+LCT 10% (F2), and P 45%+B 45%+LCT 8%+Vita E 2% (F3). Results revealed that the solubility of the VAFC was significantly increased in F3 formulation. Likewise, total phenolic content, including single phenolic acids, total flavonoid including rutin and quercetin, total anthocyanin including single anthocyanins, and antioxidant capacity of the VAFC were significantly increased in F3 formulation. This study successfully demonstrated the approach of developing biopolymer‐mediated functional VAFC from potato and buckwheat by HME. Practical applications: People are becoming more conscious about daily consumed foods and their nutritional facts. Human health requires a well‐balanced nutritional composition to keep well‐functioning of the body. In this study, an approach was taken to develop anthocyanins, and rutin‐enriched functional food by the mixes of potato and buckwheat by hot‐melt extrusion. Food biopolymers and plasticizer were added to the food formulation to enhance the activity of the extrudate composites' functional attributes. Our developed formulation successfully improved the food composite's functional quality, which required industrialization for bulk production. [ABSTRACT FROM AUTHOR]

Objective: The association between colchicine use and the primary prevention of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to explore the association between colchicine use and new development of ASCVD and ASCVD-related mortality in patients with incident gout., Methods: This nested case-control study utilized the nation-wide claims database of the Korean National Health Insurance System. Patients without a history of ASCVD who developed incident gout and were newly started on allopurinol as first-line therapy between 2011 and 2016 were initially screened. Individuals who experienced ASCVD event or ASCVD-related mortality during the follow-up period were matched with four controls for age, sex, income, residential area, co-morbidities, and medications. The main exposure was colchicine use, assessed by 1) the cumulative defined daily doses (cDDDs) and 2) the cumulative duration. For secondary analyses, the risk of ASCVD events and ASCVD-related mortality were examined, separately., Results: Overall, 9,346 patients with ASCVD event or ASCVD-related mortality were matched with 35 070 controls. The patient population was predominantly male. Compared with non-users, a curvilinear relationship between higher cDDDs of colchicine and the odds of ASCVD event was observed; the odds ratios (95% confidence interval) were were 1.09 (1.04-1.15) for <90 cDDDs, 1.20 (1.07-1.33) for 80-179 cDDDs, and 1.21 (1.09-1.35) for ≥180 cDDDs. This association was similarly observed for ASCVD events and ASCVD-related mortality, respectively., Conclusion: Colchicine use was associated with an increased risk of ASCVD in patients with newly diagnosed gout who did not have a prior history of ASCVD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction Non-alcoholic fatty liver disease (NAFLD) has emerged as a potential indicator for cardio-metabolic risk. However, clinical implications of NAFLD in patients with chronic kidney disease (CKD) are still elusive. We investigated to explore the association between NAFLD and adverse clinical outcomes among patients with CKD. Methods In this national population-based retrospective cohort study, we analyzed 816,857 individuals who underwent National Health Insurance Service health examinations and had an eGFR of 15-59 mL/min/1.73 m2. The main predictor was the fatty liver index (FLI), a surrogate marker for NAFLD. The primary outcome was a composite cardiovascular or kidney events, which were examined combined or separately. Results During a median follow-up of 7.7 (IQR, 6.4-9.6) years, the composite outcome events occurred in 74,266 (9.1%) individuals. Among these, there were 55,525 (6.8%) cardiovascular events and 22,961 (2.8%) kidney events, respectively. Compared to FLI of &lt;30, the HRs (95% CIs) for the composite outcome were 1.16 (1.14-1.18) and 1.30 (1.26-1.33) for the FLIs of 30-59 and ≥60, respectively. The corresponding HRs for cardiovascular events were 1.21 (95% CI, 1.18-1.23) and 1.36 (95% CI, 1.31-1.40), respectively. Furthermore, FLIs of 30-59 and ≥60 were associated with an 11% (HR, 1.11; 95% CI, 1.07-1.15) and 24% (HR, 1.24; 95% CI, 1.17-1.30) increased risk of kidney events, respectively. Conclusions NAFLD was associated with higher risk of adverse clinical outcomes in individuals with CKD. These findings suggest that NAFLD, as assessed by the FLI, can serve as a predictor of cardiovascular and kidney events in CKD population., (S. Karger AG, Basel.)

Background: The target blood pressure (BP) value is unclear for diabetic kidney disease (DKD). Therefore, we aimed to evaluate the effect of strict BP control or 'on treatment' BP on clinical outcomes in patients with DKD., Methods: A post-hoc analysis of the prespecified secondary outcomes of the FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial, a randomized multicenter double-blind phase III trial. Eligible patients were aged ≥ 19 years with DKD. We assigned 341 participants with DKD to BP control strategy (standard-systolic BP [SBP] < 140 mmHg versus strict-SBP < 130 mmHg). The outcome was the occurrence of cardiovascular events and renal events. Separate analyses were performed to compared the risk of outcome according to achieved average BP levels., Results: A total of 341 participants were included in the analysis. Over a median follow-up of 2.8 years, cardiovascular/renal events were observed in 25 (7.3%) participants. Mean (SD) SBPs in the standard and strict BP control group were 140.2 (11.6) and 140.2 (11.9) mmHg, respectively. The strict BP control group did not show significantly reduced risk of cardiovascular/renal events (HR 1.32; 95% CI 0.60-2.92]). In the post-hoc analyses using achieved BP, achieved average SBP of 130-139 mmHg resulted in reduced risk of cardiovascular/renal events (HR 0.15; 95% CI 0.03-0.67) compared to achieved average SBP ≥ 140 mmHg, whereas further reduction in achieved average SBP < 130 mmHg did not impart additional benefits., Conclusion: In patients with DKD, targeting a SBP of less than 130 mmHg, as compared with less than 140 mmHg, did not reduce the rate of a composite of cardiovascular and renal events. Achieved SBP of 130-139 mmHg was associated with a decreased risk for the primary outcome in patients with DKD., Trial Registration: ClinicalTirals.gov Identifier: NCT02620306, registered December 3, 2015. ( https://clinicaltrials.gov/study/NCT02620306 )., (© 2024. The Author(s).)

Background: Fluid overload is an independent risk factor of mortality in patients with acute kidney injury (AKI) receiving continuous kidney replacement therapy (CKRT). However, the association between fluid status, as assessed by bioelectrical impedance analysis (BIA) or lung ultrasound, and survival in patients with AKI requiring CKRT has not been established., Methods: We analyzed 36 participants with sepsis-associated AKI who received CKRT at a tertiary hospital. The main exposures were volume surrogates: 1) overhydration normalized by extracellular water (OH/ECW, L/L) assessed by BIA, 2) the number of B-lines measured by lung ultrasound, and 3) weight change ([body weight at CKRT initiation - body weight at admission] × 100/body weight at admission). The primary outcome was the 28-day mortality., Results: Seventeen participants (47.2%) died within 28 days. There were no significant correlations between OH/ECW and weight change (R2 = 0.040, p = 0.24), number of B-lines and OH/ECW (R2 = 0.056, p = 0.16), or weight change and number of B-lines (R2 = 0.014, p = 0.49). Kaplan-Meier analyses revealed that patients in the highest tertile of OH/ECW showed a significantly lower cumulative 28-day survival probability than the others (the lowest + middle tertiles). The survival probability of participants in the highest tertile of the number of B-lines or weight change did not differ from that of their counterparts. In a multivariate Cox proportional hazard model, the hazard ratio for the highest tertile of OH/ECW was 3.83 (95% confidence interval, 1.04-14.03)., Conclusion: Volume overload assessed using BIA (OH/ECW) was associated with the 28-day survival rate in patients with sepsis-associated AKI who received CKRT.

Background Whether visit-to-visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear. Methods and Results We investigated the relationship between SDs of visit-to-visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit-to-visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient-years of follow-up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit-to-visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80-3.36) and 2.23 (95% CI, 1.12-4.44), respectively, in a multivariable cause-specific hazard model. In addition, the HR associated with each 5-mm Hg increase in visit-to-visit SBP variability (SD) was 1.21 (95% CI, 1.01-1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03-4.35) and 2.28 (95% CI, 1.12-4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87-3.57) and 2.04 (95% CI, 1.03-4.03), respectively, with the variation independent of the mean. Conclusions Higher visit-to-visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Peroxiredoxins (Prxs) are ubiquitously expressed peroxidases that reduce hydrogen peroxide or alkyl peroxide production in cells. Prxs are released from cells in response to various stress conditions, and they function as damage-associated molecular pattern molecules. However, the secretory mechanism of Prxs and their roles have not been elucidated. Thus, we aimed to determine whether inflammasome activation is a secretory mechanism of Prxs and subsequently identify the effect of the secreted Prxs on activation of the classical complement pathway. Using J774A.1, a murine macrophage cell line, we demonstrated that NLRP3 inflammasome activation induces Prx1, Prx2, Prx5, and Prx6 secretion in a caspase-1 dependent manner. Using HEK293T cells with a transfection system, we revealed that the release of Prx1 and Prx2 relies on gasdermin-D (GSDMD)-mediated secretion. Next, we confirmed the binding of both Prx1 and Prx2 to C1q; however, only Prx2 could induce the C1q-mediated classical complement pathway activation. Collectively, our results suggest that inflammasome activation is a secretory mechanism of Prxs and that GSDMD is a mediator of their secretion. Moreover, secreted Prx1 and Prx2 bind with C1q, but only Prx2 mediates the classical complement pathway activation., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2021. The Korean Association of Immunologists.)