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Abstract The bioinspired camera, comprising a single lens and a curved image sensor—a photodiode array on a curved surface—, was born of flexible electronics. Its economical build lends itself well to space-constrained machine vision applications. The curved sensor, much akin to the retina, helps image focusing, but the curvature also creates a problem of image distortion, which can undermine machine vision tasks such as object recognition. Here we report an anti-distortion single-lens camera, where 4096 silicon photodiodes arrayed on a curved surface in a nonuniform pattern assimilated to the distorting optics are the key to anti-distortion engineering. That is, the photo-pixel distribution pattern itself is warped in the same manner as images are warped, which correctively reverses distortion. Acquired images feature no appreciable distortion across a 120° horizontal view, as confirmed by their neural-network recognition accuracies. This distortion correction via photo-pixel array reconfiguration is a form of in-sensor computing.

Purpose This study aimed to establish baseline morphological and functional data for normal mouse kidneys via a clinical 33 MHz ultra-high-frequency (UHF) transducer, compare the data with the findings from fibrotic mice, and assess correlations between ultrasonography (US) parameters and fibrosis-related markers. Methods This retrospective study aggregated data from three separate experiments (obstructive nephropathy, diabetic nephropathy, and acute-to-chronic kidney injury models). Morphological parameters (kidney size, parenchymal thickness [PT]) and functional (shear-wave speed [SWS], stiffness, resistive index [RI], and microvascular imaging-derived vascular index [VI]) were assessed and compared between normal and fibrotic mouse kidneys. Semi-quantitative histopathologic scores were calculated and molecular markers (epithelial cadherin), Collagen 1A1 [Col1A1], transforming growth factor-β, and α-smooth muscle actin [α-SMA]) were evaluated using western blots. Correlations with US parameters were explored. Results Clinical UHF US successfully imaged the kidneys of the experimental mice. A three-layer configuration was prevalent in the normal mouse kidney parenchyma (34/35) but was blurred in most fibrotic mouse kidneys (33/40). US parameters, including size (11.14 vs. 10.70 mm), PT (2.07 vs. 1.24 mm), RI (0.64 vs. 0.77), VI (22.55% vs. 11.47%, only for non-obstructive kidneys), SWS (1.67 vs. 2.06 m/s), and stiffness (8.23 vs. 12.92 kPa), showed significant differences between normal and fibrotic kidneys (P

Abstract 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.

Abstract 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]

Abstract Despite numerous studies on the effect of each dialysis modality on mortality, the issue remains controversial. We investigated the hazard rate of mortality in patients with incident end-stage renal disease (ESRD) concerning initial dialysis modality (hemodialysis vs. peritoneal dialysis). Using a nationwide, multicenter, prospective cohort in South Korea, we studied 2207 patients, of which 1647 (74.6%) underwent hemodialysis. We employed the weighted Fine and Gray model over the follow-up period using inverse probability of treatment and censoring weighting. Landmark analysis was used for identifying the changing effect of dialysis modality on individuals who remained event-free at each landmark point. No significant difference in hazard rate was observed overall. However, the peritoneal dialysis group had a significantly higher hazard rate than the hemodialysis group among patients under 65 years after 4- and 5- year follow-up. A similar pattern was observed among those with diabetes mellitus. Landmark analysis also showed the higher hazard rate for peritoneal dialysis at 2 years for the education-others group and at 3 years for the married group. These findings may inform dialysis modality decisions, suggesting a preference for hemodialysis in young patients with diabetes, especially for follow-ups longer than 3 years.

Abstract 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.

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

Abstract Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N6-methyladenosine (m6A) RNA methylation is associated with organ fibrosis. We investigated m6A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-β-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m6A levels. In the UUO model, METTL3 expression and m6A levels were significantly increased. Transcriptomic and m6A profiling demonstrated that epithelial-to-mesenchymal transition- and inflammation-related pathways were significantly associated with RNA m6A methylation. Genetic and pharmacologic inhibition of METTL3 in HK-2 cells decreased TGF-β-induced fibrotic marker expression. STM2457-induced inhibition of METTL3 attenuated the degree of kidney fibrosis in vivo. Furthermore, METTL3 protein expression was significantly increased in the tissues of CKD patients with diabetic or IgA nephropathy. Therefore, targeting alterations in RNA methylation could be a potential therapeutic strategy for treating kidney fibrosis.

Abstract Background Epidemiologic studies on the effects of long-term exposure to ozone (O3) have shown inconclusive results. It is unclear whether to O3 has an effect on chronic kidney disease (CKD). We investigated the effects of O3 on mortality and renal outcome in CKD. Methods We included 61,073 participants and applied Cox proportional hazards models to examine the effects of ozone on the risk of end-stage renal disease (ESRD) and mortality in a two-pollutants model adjusted for socioeconomic status. We calculated the concentration of ozone exposure one year before enrollment and used inverse distance weighting (IDW) for interpolation, where the exposure was evenly distributed. Results In the single pollutant model, O3 was significantly associated with an increased risk of ESRD and all-cause mortality. Based on the O3 concentration from IDW interpolation, this moving O3 average was significantly associated with an increased risk of ESRD and all-cause mortality. In a two-pollutants model, even after we adjusted for other measured pollutants, nitrogen dioxide did not attenuate the result for O3. The hazard ratio (HR) value for the district-level assessment is 1.025 with a 95% confidence interval (CI) of 1.014–1.035, while for the point-level assessment, the HR value is 1.04 with a 95% CI of 1.035–1.045. The impact of ozone on ESRD, hazard ratio (HR) values are, 1.049(95%CI: 1.044–1.054) at the district unit and 1.04 (95%CI: 1.031–1.05) at the individual address of the exposure assessment. The ozone hazard ratio for all-cause mortality was 1.012 (95% confidence interval: 1.008–1.017) for administrative districts and 1.04 (95% confidence interval: 1.031–1.05) for individual addresses. Conclusions This study suggests that long-term ambient O3 increases the risk of ESRD and mortality in CKD. The strategy to decrease O3 emissions will substantially benefit health and the environment.

Abstract 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.

Abstract Diabetic nephropathy (DN) is associated with kidney fibrosis. A previous study revealed that periostin (POSTN) contributes to kidney fibrosis. This study examined the role of POSTN in DN. The urinary concentrations of POSTN and TNC increased according to the severity of DN in human samples. Streptozotocin (STZ) was administered after unilateral nephrectomy (UNXSTZ) to induce DN in wild-type and Postn-null mice. Four experimental groups were generated: wild-typeham (WT Sham), wild-type UNXSTZ (WT STZ), Postn-null Sham (KO Sham), and Postn-null UNXSTZ (KO STZ). After 20 weeks, the KO STZ group had lower levels of urine albumin excretion, glomerular sclerosis, and interstitial fibrosis than those of the WT STZ group. Additionally, the KO STZ group had lower expression of fibrosis markers, including TNC. The KO STZ group showed better glucose regulation than the WT STZ model. Furthermore, the KO STZ group exhibited significantly preserved pancreatic islet integrity and insulin expression. HK-2 cells were used to observe the aggravation of fibrosis caused by POSTN under TGF-β conditions. We stimulated INS-1 cells with streptozotocin and evaluated the viability of these cells. The anti-POSTN antibody treatment of INS-1 cells with streptozotocin resulted in higher cell viability than that with treatment with streptozotocin alone. The absence of POSTN in DN contributes to renal fibrosis alleviation by improving pancreatic β-cell function. Additionally, there is an association between POSTN and TNC.

Abstract Decreased total CO2 (tCO2) is significantly associated with all-cause mortality in critically ill patients. Because of a lack of data to evaluate the impact of tCO2 in patients with COVID-19, we assessed the impact of tCO2 on all-cause mortality in this study. We retrospectively reviewed the data of hospitalized patients with COVID-19 in two Korean referral hospitals between February 2020 and September 2021. The primary outcome was in-hospital mortality. We assessed the impact of tCO2 as a continuous variable on mortality using the Cox-proportional hazard model. In addition, we evaluated the relative factors associated with tCO2 ≤ 22 mmol/L using logistic regression analysis. In 4,423 patients included, the mean tCO2 was 24.8 ± 3.0 mmol/L, and 17.9% of patients with tCO2 ≤ 22 mmol/L. An increase in mmol/L of tCO2 decreased the risk of all-cause mortality by 4.8% after adjustment for age, sex, comorbidities, and laboratory values. Based on 22 mmol/L of tCO2, the risk of mortality was 1.7 times higher than that in patients with lower tCO2. This result was maintained in the analysis using a cutoff value of tCO2 24 mmol/L. Higher white blood cell count; lower hemoglobin, serum calcium, and eGFR; and higher uric acid, and aspartate aminotransferase were significantly associated with a tCO2 value ≤ 22 mmol/L. Decreased tCO2 significantly increased the risk of all-cause mortality in patients with COVID-19. Monitoring of tCO2 could be a good indicator to predict prognosis and it needs to be appropriately managed in patients with specific conditions.

Thermomechanical processing (TMP) of ferritic–martensitic (FM) steels, such as HT9 (Fe–12Cr–1MoWV) steels, involves normalizing, quenching, and tempering to create a microstructure of fine ferritic/martensitic laths with carbide precipitates. HT9 steels are used in fast reactor core components due to their high-temperature strength and resistance to irradiation damage. However, traditional TMP methods for these steels often result in performance limitations under irradiation, including embrittlement at low temperatures (500 °C), and void swelling after high-dose irradiation (>200 dpa). This research aimed to enhance both fracture toughness and strength at high temperatures by creating a quenched and tempered martensitic structure with ultrafine laths and precipitates through rapid quenching and unconventional tempering. Mechanical testing revealed significant variations in strength and fracture toughness depending on the processing route, particularly the tempering conditions. Tailored TMP approaches, combining rapid quenching with limited tempering, elevated strength to levels comparable to nano-oxide strengthened ferritic alloys while preserving fracture toughness. For optimal properties in high-Cr steels for future reactor applications, this study recommends a modified tempering treatment, i.e., post-quench annealing at 500 °C or 600 °C for 1 h, possibly followed by a brief tempering at a slightly higher temperature.

The relationship between molybdenum and kidney-related disease outcomes, including hyperuricemia, is not well investigated. This study aims to determine whether molybdenum and its antioxidative property are associated with systemic inflammation and kidney-related disease parameters including hyperuricemia. Urinary molybdenum's epidemiological relationship to hyperuricemia and kidney-disease related outcomes was evaluated in 15,370 adult participants in the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2016. Individuals' urinary molybdenum levels were corrected to their urinary creatinine concentrations. The association between urinary molybdenum-to-creatinine ratio and kidney-disease related outcomes were assessed by multivariable linear and logistic regression analyses, adjusting for covariates including age, sex, ethnicity, diabetes mellitus, hypertension, body mass index, and estimated glomerular filtration rate. Antimony and tungsten were used as control trace metals. Experimentally, HK-2 cell was used to assess molybdenum's antioxidative properties. HK-2 cells were challenged with H2O2-induced oxidative stress. Oxidative stress was measured using a fluorescent microplate assay for reactive oxygen species (ROS) and antioxidation levels were assessed by measuring the expression of manganese superoxide dismutase. In the adult NHANES population, urinary molybdenum-to-creatinine ratio was significantly associated with decreased serum uric acid (β, -0.119; 95% CI, -0.148 to -0.090) concentrations, and decreased prevalence of hyperuricemia (OR, 0.73; 95% CI, 0.64-0.83) and gout (OR, 0.71; 95% CI, 0.52-0.94). Higher urinary molybdenum levels were associated with lower levels of systemic oxidative stress (gamma-glutamyltransferase levels; β, -0.052; 95% CI, -0.067 to -0.037) and inflammation (C-reactive protein levels; β, -0.184; 95% CI, -0.220 to -0.148). In HK-2 cells under H2O2-induced oxidative stress, molybdenum upregulated manganese superoxide dismutase expression and decreased oxidative stress. Urinary molybdenum levels are associated with decreased prevalence of hyperuricemia and gout in adult population. Molybdenum's antioxidative properties might have acted as an important mechanism for the reduction of systemic inflammation, ROS, and uric acid levels.

Background: Recent studies have reported that air pollution is related to kidney diseases. However, the global evidence on the risk of death from acute kidney injury (AKI) owing to air pollution is limited. Therefore, we investigated the association between short-term exposure to air pollution—particulate matter ≤ 2.5 μm (PM2.5), ozone (O3), and nitrogen dioxide (NO2)—and AKI-related mortality using a multi-country dataset. Methods: This study included 41,379 AKI-related deaths in 136 locations in six countries during 1987–2018. A novel case time-series design was applied to each air pollutant during 0–28 lag days to estimate the association between air pollution and AKI-related deaths. Moreover, we calculated AKI deaths attributable to non-compliance with the World Health Organization (WHO) air quality guidelines. Results: The relative risks (95% confidence interval) of AKI-related deaths are 1.052 (1.003, 1.103), 1.022 (0.994, 1.050), and 1.022 (0.982, 1.063) for 5, 10, and 10 µg/m3 increase in lag 0–28 days of PM2.5, warm-season O3, and NO2, respectively. The lag-distributed association showed that the risk appeared immediately on the day of exposure to air pollution, gradually decreased, and then increased again reaching the peak approximately 20 days after exposure to PM2.5 and O3. We also found that 1.9%, 6.3%, and 5.2% of AKI deaths were attributed to PM2.5, warm-season O3, and NO2 concentrations above the WHO guidelines. Conclusions: This study provides evidence that public health policies to reduce air pollution may alleviate the burden of death from AKI and suggests the need to investigate the several pathways between air pollution and AKI death.

Abstract Anti-thymocyte globulin (ATG) is currently the most widely prescribed induction regimen for preventing acute rejection after solid organ transplantation. However, the optimal dose of ATG induction regimen in Asian kidney recipients is unclear. Using the Korean Organ Transplantation Registry, we performed a retrospective cohort study of 4579 adult patients who received renal transplantation in South Korea and divided them into three groups according to the induction regimen: basiliximab group (n = 3655), low-dose ATG group (≤ 4.5 mg/kg; n = 467), and high-dose ATG group (> 4.5 mg/kg; n = 457). We applied the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) package to generate high-quality propensity score weights for intergroup comparisons. During four-year follow-ups, the high-dose ATG group had the highest biopsy-proven acute rejection rate (basiliximab 20.8% vs. low-dose ATG 22.4% vs. high-dose ATG 25.6%; P 4.5 mg/kg) was superior to basiliximab and low-dose ATG induction in terms of graft and patient survival in Asian patients undergoing kidney transplant.

Background As a leading cause of chronic kidney disease, clinical demand for noninvasive biomarkers of diabetic kidney disease (DKD) beyond proteinuria is increasing. Metabolomics is a popular method to identify mechanisms and biomarkers. We investigated urinary targeted metabolomics in DKD patients. Methods We conducted a targeted metabolomics study of 26 urinary metabolites in consecutive patients with DKD stage 1 to 5 (n = 208) and healthy controls (n = 26). The relationships between estimated glomerular filtration rate (eGFR) or urine protein-creatinine ratio (UPCR) and metabolites were evaluated. Multivariate Cox analysis was used to estimate relationships between urinary metabolites and the target outcome, end-stage renal disease (ESRD). C statistics and time-dependent receiver operating characteristics (ROC) were used to assess diagnostic validity. Results During a median 4.5 years of follow-up, 103 patients (44.0%) progressed to ESRD and 65 (27.8%) died. The median fold changes of nine metabolites belonged to monosaccharide and tricarboxylic acid (TCA) cycle metabolites tended to increase with DKD stage. Myo-inositol, choline, and citrates were correlated with eGFR and choline, while mannose and myo-inositol were correlated with UPCR. Elevated urinary monosaccharide and TCA cycle metabolites showed associations with increased morality and ESRD progression. The predictive power of ESRD progression was high, in the order of choline, myo-inositol, and citrate. Although urinary metabolites alone were less predictive than serum creatinine or UPCR, myo-inositol had additive effect with serum creatinine and UPCR. In time-dependent ROC, myo-inositol was more predictive than UPCR of 1-year ESRD progression prediction. Conclusion Myo-inositol can be used as an additive biomarker of ESRD progression in DKD.

Abstract Interleukins (ILs), key cytokine family of inflammatory response, are closely associated with kidney function. However, the causal effect of various ILs on kidney function needs further investigation. Here we show two-sample summary-level Mendelian randomization (MR) analysis that examined the causality between serum IL levels and kidney function. Genetic variants with strong association with serum IL levels were obtained from a previous genome-wide association study meta-analysis. Summary-level data for estimated glomerular filtration rate (eGFR) were obtained from CKDGen database. As a main MR analysis, multiplicative random-effects inverse-variance weighted method was performed. Pleiotropy-robust MR analysis, including MR-Egger with bootstrapped error and weighted median methods, were also implemented. We tested the causal estimates from nine ILs on eGFR traits. Among the results, higher genetically predicted serum IL-1 receptor antagonist level was significantly associated with higher eGFR values in the meta-analysis of CKDGen and the UK Biobank data. In addition, the result was consistent towards eGFR decline phenotype of the outcome database. Otherwise, nonsignificant association was identified between other genetically predicted ILs and eGFR outcome. These findings support the clinical importance of IL-1 receptor antagonist-associated pathway in relation to kidney function in the general individuals, particularly highlighting the importance of IL-1 receptor antagonist.

Abstract To overcome the intrinsic inefficiency of the von Neumann architecture, neuromorphic devices that perform analog vector–matrix multiplication have been highlighted for achieving power‐ and time‐efficient data processing. In particular, artificial synapses, of which conductance should be programmed to represent the synaptic weights of the artificial neural network, have been intensively researched to realize neuromorphic devices. Here, inspired by excitatory and inhibitory synapses, we develop an artificial optoelectronic synapse that shows both potentiation and depression characteristics triggered only by optical inputs. The design of the artificial optoelectronic synapse, in which excitatory and inhibitory synaptic phototransistors are serially connected, enables these characteristics by spatiotemporally irradiating the phototransistor channels with optical pulses. Furthermore, a negative synaptic weight can be realized without the need for electronic components such as comparators. With such attributes, the artificial optoelectronic synapse is demonstrated to classify three digits with a high recognition rate (98.3%) and perform image preprocessing via analog vector–matrix multiplication.

Health risks due to climate change are emerging, particularly from high-temperature exposure. The perceived temperature is an equivalent temperature based on the complete heat budget model of the human body. Therefore, we aimed to analyze the effect of perceived temperature on overall mortality among patients with chronic kidney disease. In total, 32,870 patients with chronic kidney disease in Seoul participated in this retrospective study (2001–2018) at three medical centers. The perceived temperature during the summer season was calculated using meteorological factors, including the air temperature near the automated weather station, dew point temperature, wind velocity, and total cloud amount. We assessed the association between perceived temperature using Kriging spatial interpolation and mortality in patients with CKD in the time-varying Cox proportional hazards model that was adjusted for sex, age, body mass index, hypertension, diabetes mellitus, estimated glomerular filtration rate, smoking, alcohol consumption, and educational level. During the 6.14 ± 3.96 years of follow-up, 3863 deaths were recorded. In multivariable analysis, the average level of perceived temperature and maximum level of perceived temperature demonstrated an increased risk of overall mortality among patients with chronic kidney disease. The concordance index for mortality of perceived temperature was higher than temperature, discomfort index, and heat index. When stratified by age, diabetes mellitus, and estimated glomerular filtration rate, patients with chronic kidney disease with young age (age

Background The genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function. Methods Mendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-density lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an inverse variance weighted method and pleiotropy-robust methods were performed. Results Summary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL decrease) was significantly associated with a decrease in eGFR (–1.67%; 95% confidence interval [CI], –2.20% to –1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed separately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%–2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated. Conclusion Genetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medication on kidney function can vary.

Abstract Background Ageing traits and frailty are important health issues in modern medicine. Evidence supporting the causal effects of tobacco smoking on various ageing traits is required. Methods This study performed Mendelian randomization (MR) analysis instrumenting 377 genetic variants associated with being an ever‐smoker at a genome‐wide significance level to test the causal estimates from tobacco smoking. The outcome data were obtained from 337 138 white British ancestry participants from the UK Biobank. Leucocyte telomere length, appendicular lean mass index, subjective walking pace, handgrip strength, and wristband accelerometry‐determined physical activity degree were collected as ageing‐related outcomes. Summary‐level MR analysis was performed using the inverse variance‐weighted method and pleiotropy‐robust MR methods, including weighted median and MR‐Egger. Observational association between the outcome traits and phenotypically being an ever‐smoker was also investigated. Results Summary‐level MR analysis indicated that a higher genetic predisposition for tobacco smoking was significantly associated with shorter leucocyte telomere length (twofold increase in prevalence of smoking towards standardized Z‐score, −0.041 [−0.054, −0.028]), lower appendicular lean mass index (−0.007 [−0.010, −0.005]), slower walking pace (ordinal category, −0.047 [−0.054, −0.033]) and lower time spent on moderate‐to‐vigorous physical activity (hours per week, −0.39 [−0.56, −0.23]). The causal estimates were non‐significant towards handgrip strength phenotype (kg, 0.074 [−0.055, 0.204]). Pleiotropy‐robust MR results generally supported the main causal estimates. The observational findings also showed significant association between being an ever‐smoker and the ageing traits. Conclusions Genetically predicted and observational tobacco smoking status are significantly associated with poor ageing phenotypes. Healthcare providers may continue to reduce tobacco use, which may be helpful in reducing the burden of ageing and frailty.

Abstract Fluid balance is a critical prognostic factor for patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). This study evaluated whether repeated fluid balance monitoring could improve prognosis in this clinical population. This was a multicenter retrospective study that included 784 patients (mean age, 67.8 years; males, 66.4%) with severe AKI requiring CRRT during 2017–2019 who were treated in eight tertiary hospitals in Korea. Sequential changes in total body water were compared between patients who died (event group) and those who survived (control group) using mixed-effects linear regression analyses. The performance of various machine learning methods, including recurrent neural networks, was compared to that of existing prognostic clinical scores. After adjusting for confounding factors, a marginal benefit of fluid balance was identified for the control group compared to that for the event group (p = 0.074). The deep-learning model using a recurrent neural network with an autoencoder and including fluid balance monitoring provided the best differentiation between the groups (area under the curve, 0.793) compared to 0.604 and 0.606 for SOFA and APACHE II scores, respectively. Our prognostic, deep-learning model underlines the importance of fluid balance monitoring for prognosis assessment among patients receiving CRRT.

AbstractBackground Acute kidney injury (AKI) in COVID-19 patients is associated with poor prognosis. Characterization of AKI by timing and trajectory and early prediction of AKI progression is required for better preventive management and the prediction of patient outcomes.Methods A total of 858 patients who were hospitalized due to coronavirus disease 2019 (COVID-19) were retrospectively enrolled from December 2020 to August 2021. The occurrence of AKI was evaluated throughout hospitalization. The hazard ratios (HRs) of mortality outcomes according to the trajectory of AKI were measured using Cox regression models after adjustment for multiple variables.Results Among 858 patients, 226 (26.3%) presented AKI at admission, and 44 (5.1%) developed AKI during hospitalization. Patients with AKI at admission or hospital-acquired AKI had a higher risk of mortality than those without AKI, with HRs of 9.87 (2.81–34.67) and 13.74 (3.57–52.84), respectively. Of 226 patients with AKI at admission, 104 (46.0%) recovered within 48 hr, 83 (36.7%) had AKI beyond 48 hr and recovered in 7 days, and 39 (17.3%) showed no recovery from AKI on Day 7. Delayed recovery and persistent AKI were significantly associated with an increased risk of mortality, with HRs of 4.39 (1.06–18.24) and 24.33 (7.10–83.36), respectively.Conclusions The onset and progression of AKI was significantly associated with in-hospital mortality in patients with COVID-19. A thorough observation of the recovery trajectory of early AKI after infection is necessary.

Abstract In patients with chronic kidney disease (CKD), coronavirus disease 2019 (COVID-19) has a higher mortality rate than the general population; therefore, prevention is vital. To prevent COVID-19 infection, it is important to study individuals’ risk aversion behavior. The objective of this study was to understand how the behavioral characteristics of physical distancing, hygiene practice, and exercise changed in patients with CKD during the COVID-19 pandemic and to identify the characteristics of patients who showed weakened or strengthened behavioral changes. We analyzed data from the Study on Kidney Disease and Environmental Chemicals (Clinical Trial No. NCT04679168), that examined a prospective cohort of patients with CKD. This cohort included patients with CKD who visited the participating hospitals for the first time between June and October 2020 and the second time between October 2020 and January 2021. Data on demographics, socio-economic details, and behavioral characteristics were collected through a questionnaire survey. Using a multivariable logistic regression model, we identified whether COVID-19 infection risk perception and previous strong behavioral changes affected behavioral changes during the first and second visits. A total of 277 patients (33.2% females) were included in the analysis. Nine out of 12 behaviors were reinforced at the first visit, and five out of nine reinforced behaviors were weakened at the second visit. A high-risk perception of COVID-19 infection was not associated with the tendency of overall behavioral reinforcement or maintaining behaviors in an enhanced state at the second visit. Strong behavioral changes at the patients’ first visit to the hospital were associated with a tendency to strengthen or maintain reinforced behaviors at the second visit (adjusted odds ratio 1.99, 95% confidence interval 1.19–3.34; P = 0.009). Even if the initial COVID-19 risk perception is high, behavioral changes worsen over time. Individuals who showed more active behavioral changes at the beginning of the COVID-19 pandemic tended to maintain reinforced behavior over time. Continuous education and monitoring are needed to maintain changed behaviors, especially in patients with a high initial COVID-19 risk perception.

Abstract Background During the coronavirus diseases 2019 (COVID-19) pandemic, population’s mortality has been affected not only by the risk of infection itself, but also through deferred care for other causes and changes in lifestyle. This study aims to investigate excess mortality by cause of death and socio-demographic context during the COVID-19 pandemic in South Korea. Methods Mortality data within the period 2015–2020 were obtained from Statistics Korea, and deaths from COVID-19 were excluded. We estimated 2020 daily excess deaths for all causes, the eight leading causes of death, and according to individual characteristics, using a two-stage interrupted time series design accounting for temporal trends and variations in other risk factors. Results During the pandemic period (February 18 to December 31, 2020), an estimated 663 (95% empirical confidence interval [eCI]: -2356–3584) excess deaths occurred in South Korea. Mortality related to respiratory diseases decreased by 4371 (3452–5480), whereas deaths due to metabolic diseases and ill-defined causes increased by 808 (456–1080) and 2756 (2021–3378), respectively. The increase in all-cause deaths was prominent in those aged 65–79 years (941, 88–1795), with an elementary school education or below (1757, 371–3030), or who were single (785, 384–1174), while a decrease in deaths was pronounced in those with a college-level or higher educational attainment (1471, 589–2328). Conclusion No evidence of a substantial increase in all-cause mortality was found during the 2020 pandemic period in South Korea, as a result of a large decrease in deaths related to respiratory diseases that offset increased mortality from metabolic disease and diseases of ill-defined cause. The COVID-19 pandemic has disproportionately affected those of lower socioeconomic status and has exacerbated inequalities in mortality.

COVID-19 is an unprecedented pandemic that has impacted the whole world. The pandemic made researchers and educators realize the critical need to prepare for future disasters. This study explored a context-specific case for elementary online learning where we investigated how elementary school teachers transitioned to emergency remote teaching (ERT) from face-to-face to online learning during the pandemic. A case study approach was used to explore South Korean elementary teachers' ERT approaches and experiences during COVID-19. Using the CIPP (Context, Input, Process, and Product) framework, we sought to understand how the transition occurred from the perspectives of the teachers. The analysis uncovered several themes that fall under each category of the framework. In terms of context, limited technological aptitude and lack of training in online instructional design as well as policy issues and socio-economic differences were identified as key factors in assessing the current state of the ERT. In terms of input, instructors' efforts as well as support from in and out of school were discussed. Student interaction and engagement were identified as key factors in understanding the process of ERT. Lastly, learning outcomes, instructional strategies, and systemic transformation emerged as products of ERT.

The present study analysed digital literacy issues encountered by elementary school teachers in remote classrooms due to COVID-19. The study sought to derive a plan for cultivating teachers' digital literacy to support students' distance education. To this end, focus group interviews were conducted with five elementary school teachers in charge of upper grades, the results were analysed, and strategies to improve teacher digital literacy were derived. Specifically, three main areas of teacher digital literacy were identified for improvement. The first was providing training to use digital devices and online platforms, develop online content, and strengthen copyright understanding. The second was providing professional development programs to train digital teaching methods or pedagogies by level and by subject characteristics. The third was activating online and offline platforms for information sharing among teachers and establish a digital teaching support system. This study will be of value to teachers and school administrations in preparing for distance education in the era of digital transformation because it presents measures to foster teachers' digital literacy required by future society.

Background Comorbid conditions impact the survival of patients with severe acute kidney injury (AKI) who require continuous renal replacement therapy (CRRT). The weights assigned to comorbidities in predicting survival vary based on type of index, disease, and advances in management of comorbidities. We developed a modified Charlson Comorbidity Index (CCI) for use in patients with AKI requiring CRRT (mCCI-CRRT) and improved the accuracy of risk stratification for mortality. Methods A total of 828 patients who received CRRT between 2008 and 2013, from three university hospital cohorts was included to develop the comorbidity score. The weights of the comorbidities were recalibrated using a Cox proportional hazards model adjusted for demographic and clinical information. The modified index was validated in a university hospital cohort (n = 919) using the data of patients treated from 2009 to 2015. Results Weights for dementia, peptic ulcer disease, any tumor, and metastatic solid tumor were used to recalibrate the mCCI-CRRT. Use of these calibrated weights achieved a 35.4% (95% confidence interval [CI], 22.1%–48.1%) higher performance than unadjusted CCI in reclassification based on continuous net reclassification improvement in logistic regression adjusted for age and sex. After additionally adjusting for hemoglobin and albumin, consistent results were found in risk reclassification, which improved by 35.9% (95% CI, 23.3%–48.5%). Conclusion The mCCI-CRRT stratifies risk of mortality in AKI patients who require CRRT more accurately than does the original CCI, suggesting that it could serve as a preferred index for use in clinical practice.

Background Growing evidence suggests that environmental air pollution adversely affects kidney health. To date, the association between carbon monoxide (CO) and mortality in patients with end-stage renal disease (ESRD) has not been examined. Methods Among 134,478 dialysis patients in the Korean ESRD cohort between 2001 and 2014, 8,130 deceased hemodialysis patients were enrolled, and data were analyzed using bidirectional, unidirectional, and time-stratified case-crossover design. We examined the association between short-term CO concentration and mortality in patients with ESRD. We used a two-pollutant model, adjusted for temperature as a climate factor and for nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter less than 10 μm in diameter as air pollution variables other than CO. Results Characteristics of the study population included age (66.2 ± 12.1 years), sex (male, 59.1%; female, 40.9%), and comorbidities (diabetes, 55.6%; hypertension, 14.4%). Concentration of CO was significantly associated with all-cause mortality in the three case-crossover designs using the two-pollutant model adjusted for SO2. Patients with diabetes or age older than 75 years had a higher risk of mortality than patients without diabetes or those younger than 75 years. Conclusion Findings presented here suggest that higher CO concentration is correlated with increased all-cause mortality in hemodialysis patients, especially in older high-risk patients.

Background/Aims Renal recovery of a kidney donor after undergoing nephrectomy though challenging is essential. We aimed to examine the effect of estimated glomerular filtration rate (eGFR) percent change at 1-month post-donation on insufficient kidney function after kidney donation. Methods A total of 3,952 living kidney donors who underwent donor nephrectomy from 1982 to 2019 from eight different tertiary hospitals in Korea were initially screened. Percent changes in the eGFR from baseline to 1-month post-donation were calculated. The degree of percent changes was categorized by quartile, and the 1st quartile was regarded as the group with the lowest decreased eGFR at 1-month after donation. The remaining eGFR less than 60 mL/min/1.73 m2 was the end-point. The Cox proportional hazard model was used for evaluating the impact of initial eGFR and eGFR percent change at 1-month post-donation on the condition with remaining eGFR < 60 mL/min/1.73 m2. In the multivariate analysis, we used variables with a p < 0.1 in the univariate analysis. Results A total of 1,585 donors were included in the analysis. During 62.2 ± 49.3 months, 13.7% of donors showed renal insufficiency. The 4th (adjusted hazard ratio [aHR], 10.41; 95% confidence interval [CI], 5.15 to 21.04) and the 3rd (aHR, 4.29; 95% CI, 2.15 to 8.56) quartiles of percent change in eGFR and the pre-donation eGFR (aHR, 0.90; 95% CI, 0.88 to 0.92) were associated with the development of renal insufficiency. Conclusions The impact of worse initial renal recovery on renal insufficiency was pronounced in donors with lower pre-donation eGFRs. Additionally, worse initial renal recovery of remaining kidney affected the long-term development of renal insufficiency in kidney donors.

Mendelian randomization analyses of estimated glomerular filtration rate (eGFR) in the UK Biobank cohort provide insight into the causal effects of kidney function on 60 biochemical parameters.

Abstract Despite interest in the clinical implications of soluble transferrin receptor (sTfR), previous studies on the association of sTfR with mortality in the general population are lacking. Therefore, we analysed the association between sTfR and all-cause mortality in the general United States adult population. We conducted a prospective cohort study using National Health and Nutrition Examination Survey data from 2003 to 2010. A total of 5403 premenopausal nonpregnant females were analysed in this study. The mean age was 34.2 years (range 20.0–49.9 years). Participants were divided into log(sTfR) tertiles. The primary outcome was all-cause mortality. The secondary outcome was chronic kidney disease (CKD) development (composite of estimated glomerular filtration rate 0.57, hazard ratio [HR] 1.77 [95% CI 1.05–2.98]) in a multivariable hazards model including covariates such as haemoglobin and ferritin. Patients in the highest tertile of log(sTfR) also had an increased risk of CKD relative to those in the reference tertile. High sTfR was associated with all-cause mortality and CKD regardless of anaemia and iron storage status.

Background The recent novel coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented changes in behavior. We evaluated the current status of precautionary behavior and physical activity in chronic kidney disease (CKD) patients during the COVID-19 pandemic. Methods A population of CKD patients (n = 306) registered in the Study on Kidney Disease and Environmental Chemicals (SKETCH, Clinical Trial No. NCT04679168) cohort recruited from June 2020 to October 2020 was included in the study. We conducted a questionnaire survey related to risk perception of COVID-19, precautionary behavior, and physical activity. Results There were 187 patients (61.1%) with estimated glomerular filtration rate of

Background Shared decision-making is a two-way symmetrical communication process in which clinicians and patients work together to achieve the best outcome. This study aimed to develop self-assessment items as a decision aid for choosing a dialysis modality in patients with chronic kidney disease (CKD) and to assess the construct validity of the newly developed items. Methods Five focus group interviews were performed to extract specific self-assessment items regarding patient values in choosing a dialysis modality. After survey items were refined, a survey of 330 patients, consisting of 152 hemodialysis (HD) and 178 peritoneal dialysis (PD) patients, was performed to validate the self-assessment items. Results The self-assessment for the decision aid was refined to 35 items. The structure of the final items appeared to have three dimensions of factors; health, lifestyle, and dialysis environment. The health factor consisted of 12 subscales (α = 0.724), the lifestyle factor contained 11 subscales (α = 0.624), and the dialysis environment factor was represented by 12 subscales (α = 0.694). A structural equation model analysis showed that the relationship between the decision aid factors (health, lifestyle, and dialysis environment), patients’ CKD perception, and cognition of shared decision-making differed between HD patients and PD patients. Conclusion We developed and validated self-assessment items as part of a decision aid to help patients with CKD. This attempt may assist CKD patients in making informed and shared decisions closely aligned with their values when considering dialysis modality.

Background: Recent studies have identified the association of environmental stressors with reduced kidney function and the development of kidney disease. While residential greenness has been linked to many health benefits, the association between residential greenness and the development of kidney disease is not clear. We aimed to investigate the association between residential greenness and the development of kidney disease. Methods: We performed a longitudinal population-based cohort study including all fee-for-service Medicare Part A beneficiaries (aged 65 years or older) in Massachusetts (2000–2016). We assessed greenness with the annual average Enhanced Vegetation Index (EVI) based on residential ZIP codes of beneficiaries. We applied Cox-equivalent Poisson models to estimate the association between EVI and first hospital admission for total kidney disease, chronic kidney disease (CKD), and acute kidney injury (AKI), separately. Results: Data for 1,462,949 beneficiaries who resided in a total of 644 ZIP codes were analyzed. The total person-years of follow-up for total kidney disease, CKD, and AKI were 9.8, 10.9, and 10.8 million person-years, respectively. For a 0.1 increase in annual EVI, the hazard ratios (HRs) were 0.95 (95% CI: 0.93 to 0.97) for the first hospital admission for total kidney disease, and the association was more prominent for AKI (HR: 0.94 with 95% CI: 0.92 to 0.97) than CKD (HR: 0.98 with 95% CI: 0.95–1.01]). The estimated effects of EVI on kidney disease were generally more evident in White beneficiaries and those residing in metropolitan areas compared to the overall population. Conclusions: This study found that higher levels of annual residential greenness were associated with a lower risk of the first hospital admission for kidney diseases. Results are consistent with the hypothesis that higher residential greenness benefits kidney patients.

Background Hepatocyte growth factor (HGF)/cMet pathway is necessary for repair and regeneration following acute kidney injury (AKI). We evaluated the clinical potential of plasma HGF and soluble cMet as prognostic biomarkers for severe AKI requiring continuous renal replacement therapy (CRRT). Methods One hundred thirty-six patients with severe AKI who participated in the VENUS (volume management under body composition monitoring in critically ill patients on CRRT) trial between 2017 and 2019 were enrolled in this study. We investigated associations between plasma HGF and cMet concentrations and all-cause mortality. Results Plasma HGF and soluble cMet levels were positively correlated. Patients were divided into three groups based on their HGF and soluble cMet concentrations. The day D 0, D2, and D7 highest concentration HGF groups had significantly higher in-hospital mortality after adjusting for sex, body mass index, Acute Physiology and Chronic Health Evaluation II, and age-adjusted Charlson comorbidity index score, especially on D7 (hazard ratio, 4.26; 95% confidence interval, 1.71–10.62; p = 0.002). D7 soluble cMet level was also associated with mortality. Receiver operating characteristic curve analysis indicated that D7 HGF and soluble cMet levels were best at predicting mortality. Addition of plasma HGF and soluble cMet to conventional prognostic indices significantly improved the predictive value for mortality on D7. However, plasma HGF and soluble cMet were not associated with fluid status. Conclusion Plasma HGF and soluble cMet levels were significant predictors of the outcomes of severe AKI patients undergoing CRRT. There was no correlation between plasma HGF and soluble cMet levels and fluid balance.

Abstract The association between increased red blood cell distribution width (RDW) and mortality among patients treated on an outpatient basis in the nephrology outpatient clinic is unclear. Therefore, our study aimed to investigate the association between baseline and time-averaged RDW and mortality risk in patients treated in our nephrology outpatient clinic. Our multi-center retrospective analysis was based on data of 16,417 outpatient nephrology patients with available baseline renal function and RWD values. The median baseline RDW was 13.0% (range, 10.0–32.1%). The high-RDW group was defined as the top quartile (≥ 13.8%, n = 4302). The crude mortality rate was 15.0% (n = 1806) at a median follow-up of 127.5 months. From the results of the multivariate Cox proportional hazards regression model adjusted for covariates, including eGFR, hemoglobin, and factors of anemia treatment, patients with a high time-averaged RDW had increased mortality risk (adjusted hazard ratio, 1.505; 95% confidence interval, 1.326–1.708; P 45 years treated on an outpatient basis in the nephrology clinic.