Bioimpedance-Guided Fluid Removal in Continuous Kidney Replacement Therapy: The VENUS Randomized Clinical Trial.

BACKGROUND: Ultrafiltration with continuous kidney replacement therapy (CKRT) can be used to manage fluid balance in critically ill patients with acute kidney injury (AKI). We aimed to assess whether bioimpedance analysis (BIA)-guided volume management was more efficacious than conventional management for achieving estimated euvolemia (e-euvolemia) in CKRT-treated patients. METHODS: In a multi-center randomized controlled trial from July 2017 to July 2020, the patients with AKI requiring CKRT were eligible if the weight at the start of CKRT had increased by ≥5% compared to the weight at the time of admission, or total body water (TBW)/ height (H)2 ≥13 L/m2. We randomly assigned 208 patients to the control (conventional fluid management; N=103) and intervention groups (BIA-guided fluid management; N=105). Primary outcome was the proportion of attaining e-euvolemia seven days post-randomization. E-euvolemia was defined as the difference between TBW/H2 D7 and D0 was <-2.1 L/m2, or when TBW/H2 measured on D7 was <13 L/m2. The 28-, 60-, and 90-day mortality rate were secondary outcomes. RESULTS: The primary outcome occurred in 34 patients in the intervention group and 27 in the control group (47% versus 41%; P=0.50). The mean value of TBW/H2 measured on D7 was the same at 13.9 L/m2 in both groups. The differences between TBW/H2 D7 and D0 were -1.13 L/m2 in the intervention group and -1.08 L/m2 in the control group (P=0.84). Patients in the intervention group had a significantly higher proportion of reaching e-euvolemia on D1 than those in the control group (13% versus 4%, P=0.02). Adverse events did not differ significantly between the groups. CONCLUSIONS: BIA-guided volume management did not affect the proportion of reaching the estimated euvolemia at seven days of the start of CKRT. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03330626 (Registered on 6 November 2017; Seven study participants were retrospectively registered; nonetheless, IRB approval of each institution was completed before study participant registration).

Association Between Secondhand Smoke Exposure and the Incidence of Stroke in never smoker According to Alcohol Intake: 19-year prospective cohort study in Korea.

OBJECTIVES: Our study aimed to investigate both the independent and combined effects of second-hand smoking (SHS) and alcohol intake on the occurrence of stroke. METHODS: Utilizing the Korean Genome Epidemiology Study (KoGES) prospective cohort data, our primary exposure variables were SHS exposure and alcohol intake. The occurrence of stroke served as the main outcome of interest. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression analysis. To assess the synergistic influence of SHS and alcohol intake on stroke incidence, a joint test was conducted. RESULTS: SHS exposure correlated with an HR of 1.53 (95% CI, 1.19-1.98) for stroke risk. The combined exposure to SHS and alcohol yielded an elevated stroke risk with an HR of 1.75 (95% CI, 1.20-2.55). CONCLUSIONS: Our research highlights the combined influence of SHS exposure and alcohol intake on stroke susceptibility.

Validation of neuron-specific enolase in cardiac arrest patients with limited withdrawal of life-sustaining therapy.

Aim: We validated the prognostic performance of neuron-specific enolase (NSE) according to the recommended values in cardiac arrest (CA) survivors. Methods: We analyzed the data of adult CA survivors who underwent targeted temperature management between January 2014 and December 2020. We measured the NSE level 48 h and 72 h after CA. We performed receiver operating characteristics (ROC) and used the reference value (17 µg/L) and the guidelines-suggested value (60 µg/L) as thresholds. The primary outcome was 6-month neurological outcomes with Cerebral Performance Category (CPC), dichotomized into good (CPC 1 or 2) or poor (CPC 3-5). Results: Of the 513 included patients, 346 (67.4 %) patients had poor neurological outcomes. The area under ROC (AUC) of NSE at 48 h was 0.887 (95 % confidence intervals [CIs], 0.851-0.909) with the Youden index of 35.6 µg/L. A false positive rate (FPR) of <2 % was observed (54.1 µg/L). The thresholds values (17, 60) had a sensitivity of 86.1% and 56.7 % and a specificity of 66.7%and 98.8 %, respectively. The AUC of NSE at 72 h was 0.892 (95 % CIs, 0.849-0.920) with the Youden index of 30.4 µg/L. The threshold values (17, 60) had a sensitivity of 86.0%and 59.4 % with a specificity of 72.2%and 98.3 %, respectively. An FPR of <2 % was observed (53.6 µg/L). Among the 156 patients and 113 patients with NSE at 48 h and at 72 h ≤ 17 µg/L, respectively, 109 and 83 patients had good neurological outcomes. Conclusions: The cut-off value of NSE (60 µg/L) was acceptable to predict poor neurological outcomes with an FPR <2 % in cardiac arrest survivors, irrespective of at 48 or 72 h. NSE (17 µg/L) can function as mitigating factor to deter early WLST.

Acute kidney injury as a prognostic predictor of in-hospital mortality and neurological outcomes in patients after extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly being applied to patients with refractory cardiac arrest, but the survival rate to hospital discharge is only approximately 29%. Because ECPR requires intensive resources, it is important to predict outcomes. We therefore investigated the prognostic association between acute kidney injury (AKI) and ECPR to confirm the performance of AKI as a prognostic predictor of in-hospital mortality and neurological outcomes in ECPR. METHODS: We conducted a retrospective observational study on patients undergoing ECPR for cardiac etiology at Chonnam National University Hospital from 2015 to 2021. The group diagnosed with AKI in any KDIGO category within the first 48 h after ECPR was compared to that without AKI, and the primary outcome of the study was in-hospital mortality. RESULTS: Of 138 enrolled patients, 83 were studied. Hospital mortality occurred in 49 patients (59%), and 55 (66.3%) showed poor neurological outcomes. The AKI group displayed significantly elevated in-hospital mortality (77.8% vs 24.1%) and poor neurological outcomes (81.5% vs 37.9%) compared to the non-AKI group (p < 0.001). Regression analysis showed that AKI was associated with significantly higher rates of both in-hospital mortality (odds ratio (OR) range 10.75-12.88) and neurologic outcomes (OR range 5.9-6.22). CONCLUSIONS: There was a significant association of AKI with both in-hospital mortality and poor neurologic outcome in patients after ECPR, and AKI can be used as an early prognostic predictor in these patients.

Urine complement proteins are associated with kidney disease progression of type 2 diabetes in Korean and American cohorts.

Background: Mechanisms of progression of diabetic kidney disease (DKD) are not completely understood. This study uses untargeted and targeted mass spectrometry-based proteomics in two independent cohorts on two continents to decipher the mechanisms of DKD in patients with type 2 diabetes. Methods: We conducted untargeted mass spectrometry on urine samples collected at the time of kidney biopsy from Korean patients with type 2 diabetes and biopsy-proven diabetic nephropathy at Seoul National University Hospital (SNUH-DN cohort; n = 64). These findings were validated using targeted mass spectrometry in urine samples from a Chronic Renal Insufficiency Cohort subgroup with type 2 diabetes and DKD (CRIC-T2D; n = 282). Urinary biomarkers/pathways associated with kidney disease progression (doubling of serum creatinine, ≥50% decrease in estimated glomerular filtration rates, or the development of end-stage kidney disease) were identified. Results: SNUH-DN patients had an estimated glomerular filtration rate (eGFR) of 55 mL/min/1.73 m 2 (interquartile range [IQR], 44-75) and random urine protein-to-creatinine ratio of 3.1 g/g (IQR, 1.7-7.0). Urine proteins clustered into two groups, with cluster 2 having a 4.6-fold greater hazard (95% confidence interval [CI], 1.9-11.5) of disease progression than cluster 1 in multivariable-adjusted, time-to-event analyses. Proteins in cluster 2 mapped to 10 pathways, four of the top five of which were complement or complement-related. A high complement score, constructed from urine complement protein abundance, was strongly correlated to 4 of 5 histopathologic DN features and was associated with a 2.4-fold greater hazard (95% CI, 1.0-5.4) of disease progression than a low complement score. Targeted mass spectrometry of the CRIC-T2D participants, who had an eGFR of 42 mL/min/1.73 m 2 (IQR, 37-49) and 24-hr urine protein of 0.48 g (IQR, 0.10-1.87), showed that the complement score similarly segregated them into rapid and slow DKD progression groups. In both cohorts, the complement score had a linear association with disease progression. Conclusions: Urinary proteomic profiling confirms the association between the complement pathway and rapid DKD progression in two independent cohorts. These results suggest a need to further investigate complement pathway inhibition as a novel treatment for DKD.

Impact of hyperuricemia on CKD risk beyond genetic predisposition in a population-based cohort study.

The bidirectional effect of hyperuricemia on chronic kidney disease (CKD) underscores the importance of hyperuricemia as a risk factor for CKD. We evaluated the effect of hyperuricemia on the presence and development of CKD after considering genetic background by calculating polygenic risk scores (PRSs). We employed genome-wide association study summary statistics-excluding the United Kingdom Biobank (UKB) datasets among published CKD Gen Consortium papers-to calculate the PRSs for CKD in white background subjects. To validate PRS performance, we divided the UKB into two datasets to validate and test the data. We used logistic regression analysis to evaluate the association between hyperuricemia and CKD, and performed Kaplan-Meier survival analysis exclusively for subjects with available follow-up data. In total, 438,253 clinical data and 4,307,940 single nucleotide polymorphisms from 459,155 samples were included. We observed a significant positive association between PRS and CKD and the presence and development of CKD. Hyperuricemia significantly increased CKD risk (adjusted odds ratio 1.55, 95% confidence interval 1.48-1.61). The impact of hyperuricemia on CKD was maintained irrespective of PRS range. In addition, negative interaction between hyperuricemia and PRS for CKD was found. Survival analysis indicates that the presence of hyperuricemia significantly increased the risk of CKD development. The PRS for CKD thoroughly reflects the risk of CKD development. Hyperuricemia is a significant indicator of CKD risk, even after incorporating the genetic risk score for CKD. Irrespective of genetic risk, patients with a prospective risk of developing CKD require uric acid monitoring and management.

Protective effect of Cyclo(His-Pro) on peritoneal fibrosis through regulation of HDAC3 expression.

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.

Surviving the cold: Assessing long-term outcomes among Korean CKD patients exposed to low perceived temperature during winter.

Perceived temperature (PT), which encompasses meteorological factors such as wind speed, cloud cover, and humidity, reflects the actual effect of temperature on the human body. However, limited data exist on the health implications of prolonged exposure to low temperatures during winter in individuals with chronic kidney disease (CKD). We investigated the association between winter PT and long-term outcomes among CKD patients. A total of 32,870 CKD patients from three tertiary hospitals in Seoul were enrolled in this retrospective study (2001-2018). PT was calculated using Staiger's equation, integrating temperature data from 29 automated weather stations across Seoul, along with dew point temperature, wind velocity, and cloud cover data. Kriging interpolation was utilized to estimate PT values at the patients' locations. Overall mortality and major adverse cardiovascular events (MACEs) were assessed using a time-varying Cox proportional hazards model. Additionally, the Cox regression model evaluated PT corresponding to temperature thresholds for cold surge watches or warnings. Over a median follow-up of 6.14 ± 3.96 years, 6147 deaths (18.7%) were recorded. We found that as the average or minimum PT and Ta decreased by 1 °C, the risk of overall mortality significantly increased. In multivariable analyses, the hazard ratio (HR) for the average PT was 1.049 (95% confidence interval [CI] 1.028-1.071), and that for the minimum PT was 1.038 (CI 1.027-1.052). Furthermore, a cold surge warning at a PT of -25.63 °C indicated an HR of 1.837 (CI 1.764-1.914) and a C-index of 0.792. The increased risk of mortality was more pronounced in patients with low or middle socioeconomic statuses. For MACEs, lower average and minimum PT and Ta were associated with an increased risk, following a similar trend to overall mortality, although not all results reached statistical significance. These findings emphasize the importance of targeted public health policies to mitigate risks among vulnerable CKD patients.

Blood pressure control in diabetic kidney disease: a post-hoc analysis of the FANTASTIC trial.

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 ).

Oral phosphate binders and incident osteoporotic fracture in patients on dialysis.

BACKGROUND AND HYPOTHESIS: End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients. METHODS: We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both calcium and non-calcium-based binders (Mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality. RESULTS: Out of 69 368 incident dialysis patients, 22 326, 5020, 2853, and 39 169 were included in the CBPB, NCBPB, mixed, and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared to non-users. Specifically, only the CBPB group showed a reduced risk of vertebral (adjusted hazard ratio (aHR) 0.83 [0.76-0.92]), hip (aHR 0.81 [0.74-0.89]), and distal radius (aHR 0.88 [0.78-0.99]) fractures compared to non-users. This relationship was represented by a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months (aHR 0.9 [0.83-0.99]) and ≥ 6 months (aHR 0.83 [0.78-0.89]), compared to those using CBPB for less than 3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest, and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared to non-users. CONCLUSIONS: Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared to non-users.

Sex disparity in stroke risk among patients with insomnia: a 19-year prospective cohort study.

STUDY OBJECTIVES: Considering the increased prevalence and more severe manifestations of insomnia among females along with established sex differences in ischemic stroke (IS) occurrence, this research aimed to examine the potential effects of the interaction between insomnia and sex on the incidence and outcome of IS. METHODS: We used data from the Korean Genome and Epidemiology Study (KoGES). The main exposure variables were insomnia history and sex. The main outcome was the occurrence of IS observed in biennial follow-up surveys. Cox proportional regression analysis was performed to estimate the effects of insomnia and sex on IS incidence. We also conducted interaction analysis to investigate the interaction effects between insomnia and sex on IS incidence. RESULTS: During 19 years of follow-up involving 8,933 individuals, we documented 370 cases of new-onset stroke (2.88 cases per 1,000 person-years). Cox proportional regression analysis showed that insomnia and female sex did not increase the risk of IS (HR: 1.13 [95% CI: 0.86-1.51] and HR: 0.86 [95% CI: 0.63-1.17], respectively). Interaction analysis demonstrated that stroke risk was increased only among females with insomnia (HR: 1.34 [95%: 1.05-1.80]) compared with those without insomnia. CONCLUSIONS: Our study highlights the significance of considering sex-specific factors when evaluating the relationship between insomnia and IS risk, particularly emphasizing the unique role of insomnia in IS risk among females.

Glomerular crescents are associated with the risk of type 2 diabetic kidney disease progression: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. METHODS: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. RESULTS: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. CONCLUSION: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.

Risk of mortality and cause of death according to kidney function parameters: a nationwide observational study in Korea.

BACKGROUND: Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. METHODS: We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. RESULTS: The hazard ratio of death was significantly high in both the eGFR <60 mL/min/1.73 m2 and in the eGFR ≥120 mL/ min/1.73 m2 groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90-120 mL/min/1.73 m2). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. CONCLUSION: We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.

Associations of MRI-derived kidney volume, kidney function, body composition and physical performance in ≈38 000 UK Biobank participants: a population-based observational study.

Background: Kidney volume is used as a predictive and therapeutic marker for several clinical conditions. However, there is a lack of large-scale studies examining the relationship between kidney volume and various clinicodemographic factors, including kidney function, body composition and physical performance. Methods: In this observational study, MRI-derived kidney volume measurements from 38 526 UK Biobank participants were analysed. Major kidney volume-related measures included body surface area (BSA)-adjusted total kidney volume (TKV) and the difference in bilateral kidneys. Multivariable-adjusted linear regression and cubic spline analyses were used to explore the association between kidney volume-related measures and clinicodemographic factors. Cox or logistic regression was used to identify the risks of death, non-kidney cancer, myocardial infarction, ischaemic stroke and chronic kidney disease (CKD). Results: The median of BSA-adjusted TKV and the difference in kidney volume were 141.9 ml/m2 [interquartile range (IQR) 128.1-156.9] and 1.08-fold (IQR 1.04-1.15), respectively. Higher BSA-adjusted TKV was significantly associated with higher estimated glomerular filtration rate {eGFR; ß = 0.43 [95% confidence interval (CI) 0.42-0.44]; P < .001}, greater muscle volume [ß = 0.50 (95% CI 0.48-0.51); P < .001] and greater mean handgrip strength [ß = 0.15 (95% CI 0.13-0.16); P < .001] but lower visceral adipose tissue volume [VAT; ß = -0.09 (95% CI -0.11 to -0.07); P < .001] in adjusted models. A greater difference in bilateral kidney volumes was associated with lower eGFR, muscle volume and physical performance but with higher proteinuria and VAT. Higher BSA-adjusted TKV was significantly associated with a reduced risk of CKD [odds ratio (OR) 0.7 (95% CI 0.63-0.77); P < .001], while a greater difference in kidney volume was significantly associated with an increased risk of CKD [OR 1.13 (95% CI 1.07-1.20); P < .001]. Conclusion: Higher BSA-adjusted TKV and lower differences in bilateral kidney volumes are associated with higher kidney function, muscle volume and physical performance and a reduced risk of CKD.

Inhibition of sodium-glucose cotransporter-2 and liver-related complications in individuals with diabetes: a Mendelian randomization and population-based cohort study.

BACKGROUND AND AIMS: No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes. APPROACH AND RESULTS: Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score-matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70-0.98, p =0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60-0.90, p =0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79-0.97, p =0.01), and this difference remained significant (adjusted hazard ratio=0.72-0.89, all p <0.05) across various sensitivity analyses. CONCLUSIONS: Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.

The estimated mediating roles of anemia-related variables in the association between kidney function and mortality: a National Health and Nutrition Examination Survey (NHANES) study.

Anemia is a common complication of chronic kidney disease (CKD), impacting long-term outcomes such as mortality and morbidity. Analyzing NHANES data from 1999 through 2016 for adults aged ≥ 20 years, we assessed the mediating effects of anemia biomarkers (hemoglobin, hematocrit, red cell distribution width [RDW], and mean corpuscular hemoglobin concentration [MCHC]) on CKD-related outcomes by using hazard ratios from a biomarker-adjusted model. Of 44,099 participants, 7463 experienced all-cause death. Cox proportional hazard models revealed a higher all-cause mortality risk in the > 45 years and CKD groups than in the early CKD group. Hemoglobin, hematocrit and MCHC were inversely related to all-cause mortality; RDW was related to mortality. Single mediation analysis showed greater mediating effects of anemia indicators on CKD and mortality in the elderly (> 65 years) population than those in the general population. In the multimediation analysis, the combined mediating effect of anemia was higher in the CKD population than in the general population. This study showed a proportional increase in the mediating effect of anemia with CKD stage, suggesting potential therapeutic avenues. However, further exploration of other mediating factors on kidney outcomes is necessary.

Role of the National Early Warning score and Modified Early Warning score for predicting mortality in geriatric patients with non-traumatic coma.

Geriatric patients arriving in a non-traumatic coma (NTC) at the emergency department (ED) present substantial risks and necessitate prompt and appropriate care. The National Early Warning Score (NEWS) is a promising tool that can efficiently evaluate this vulnerable population. Current study was designed to assess the effectiveness of the NEWS for predicting the severity of illness in geriatric patients with NTC and identifying those at highest risk. Current study was performed involving geriatric patients (aged ≥65 years) with NTC who visited Chonnam National University Hospital between January and December 2022. NEWS and Modified Early Warning Scores (MEWS) were calculated at ED visits. The association of NEWS and MEWS for in-hospital death was evaluated by multivariable analysis. Out of 683 patients, 202 were non-survivors (29.6%). The NEWS and MEWS values of non-survivors were higher than those of survivors (NEWS, 7 [5-10] vs. 10 [8-12]; MEWS, 5 [4-6] vs. 7 [5-8]). The NEWS (adjusted odds ratio [aOR]; 1.253, 95% confidence interval [CI]: 1.181-1.329) and MEWS (aOR; 1.323, 95% CI: 1.206-1.451) were also significantly associated with in-hospital death. The area under the curve for the NEWS and MEWS was 0.721 (95% CI: 0.685-0.754) and 0.695 (95% CI: 0.659-0.730), respectively. The NEWS can be an effective tool for predicting severity of illness via in-hospital death in geriatric patients with NTC.

Mortality associated with the neutrophil-lymphocyte ratio in septic acute kidney injury requiring continuous renal replacement therapy.

BACKGROUND: Sepsis is an important cause of acute kidney injury in intensive care unit patients, accounting for 15% to 20% of renal replacement therapy prescriptions. The neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammation and immune response, was previously associated with the mortality rate in multiple conditions. Herein, we aimed to examine how the NLR relates to the mortality rate in septic acute kidney injury patients requiring continuous renal replacement therapy (CRRT). METHODS: The NLRs of 6 and 18 were used for dividing NLRs into three groups and, thus, were set higher than those in previous studies accounting for steroid use in sepsis. Cox proportional hazard models were used to calculate hazard ratios of mortality outcomes before and after matching their propensity scores. RESULTS: A total of 798 septic acute kidney injury patients requiring CRRT were classified into three NLR groups (low, <6 [n = 277]; medium, ≥6 and <18 [n = 115], and high, ≥18 [n = 406], respectively). The in-hospital mortality rates per group were 83.4%, 74.8%, and 70.4%, respectively (p < 0.001). Per the univariable Cox survival analysis after propensity score matching, a high NLR was related to approximately 24% reduced mortality. The survival benefit of the high NLR group compared with the other two groups remained consistent across all subgroups, showing any p for interactions of >0.05. CONCLUSION: A high NLR is associated with better clinical outcomes, such as low mortality, in septic acute kidney injury patients undergoing CRRT.

Evaluation of risk stratification for acute kidney injury: a comparative analysis of EKFC, 2009 and 2021 CKD-EPI glomerular filtration estimating equations.

BACKGROUND: The adoption of the 2021 CKD-EPIcr equation for glomerular filtration rate (GFR) estimation provided a race-free eGFR calculation. However, the discriminative performance for AKI risk has been rarely validated. We aimed to evaluate the differences in acute kidney injury (AKI) prediction or reclassification power according to the three eGFR equations. METHODS: We performed a retrospective observational study within a tertiary hospital from 2011 to 2021. Acute kidney injury was defined according to KDIGO serum creatinine criteria. Glomerular filtration rate estimates were calculated by three GFR estimating equations: 2009 and 2021 CKD-EPIcr, and EKFC. In three equations, AKI prediction performance was evaluated with area under receiver operator curves (AUROC) and reclassification power was evaluated with net reclassification improvement analysis. RESULTS: A total of 187,139 individuals, including 27,447 (14.7%) AKI and 159,692 (85.3%) controls, were enrolled. In the multivariable regression prediction model, the 2009 CKD-EPIcr model (continuous eGFR model 2, 0.7583 [0.755-0.7617]) showed superior performance in AKI prediction to the 2021 CKD-EPIcr (0.7564 [0.7531-0.7597], < 0.001) or EKFC model in AUROC (0.7577 [0.7543-0.761], < 0.001). Moreover, in reclassification of AKI, the 2021 CKD-EPIcr and EKFC models showed a worse classification performance than the 2009 CKD-EPIcr model. (- 7.24 [- 8.21-- 6.21], - 2.38 [- 2.72-- 1.97]). CONCLUSION: Regarding AKI risk stratification, the 2009 CKD-EPIcr equation showed better discriminative performance compared to the 2021 CKD-EPIcr equation in the study population.

Performance evaluation of Chronic Kidney Disease Epidemiology Collaboration equations for estimated glomerular filtration rate compared to inulin clearance in Koreans.

Background: A race-free glomerular filtration rate (GFR) estimation equation has recently been developed. However, the performance of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations needs to be evaluated in Asian populations. Methods: We performed a cross-sectional study at a single center in South Korea. The measured GFR (mGFR) was determined based on systemic inulin clearance. The GFR was estimated using the five CKD-EPI equations: 2009 CKD-EPIcr, 2012 CKD-EPIcr-cys, 2012 CKD-EPIcys, 2021 CKD-EPIcr, and 2021 CKD-EPIcr-cys. The performances of five estimated GFR (eGFR) equations were assessed by bias, precision, and accuracy (percentage of estimates within 30% of mGFR). Results: The median mGFR and interquartile range (IQR) was 53.5 (32.4-80.0) mL/min/1.73 m2. The mGFR better correlated with 2009 CKD-EPIcr (ρ = 0.628) and 2021 CKD-EPIcr-cys (ρ = 0.806) than with 2021 CKD-EPIcr (ρ = 0.623) and 2012 CKD-EPIcr-cys (ρ = 0.801). The median bias of 2009 CKD-EPIcr and 2012 CKD-EPIcr-cys were lower than those of 2021 CKD-EPI equations (2009 CKD-EPIcr, 2.24 [IQR, -8.83 to 17.39] vs. 2021 CKD-EPIcr, 5.40 [IQR, -6.04 to 20.40]; 2012 CKD-EPIcr-cys, 6.74 [IQR, -2.81 to 20.80] vs. 2021 CKD-EPIcr-cys, 10.54 [IQR, 0.30-24.37]; all in mL/min/1.73 m2). The percentage of eGFR values within 30% of mGFR was higher in 2009 CKD-EPIcr and 2012 CKD-EPIcr-cys equations than 2021 CKD-EPI equations. The CKD prevalence in 2009 CKD-EPIcr, 2021 CKD-EPIcr, 2012 CKD-EPIcr-cys, and 2021 CKD-EPIcr-cys was 54.8%, 51.0%, 47.7%, and 44.8%, respectively. Conclusion: Our study demonstrated better performance of the original CKD-EPIcr and CKD-EPIcr-cys equations than the 2021 new CKD-EPI equations. We do not recommend the adoption of the new CKD-EPI equations in Korea.