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Abstract Background The prognostic nutritional index (PNI), integrating nutrition and inflammation markers, has been increasingly recognized as a prognostic predictor in diverse patient cohorts. Recently, its effectiveness as a predictive marker for acute kidney injury (AKI) in various clinical settings has gained attention. This study aims to assess the predictive accuracy of the PNI for AKI in critically ill populations through systematic review and meta-analysis. Methods A systematic review was conducted using the databases MEDLINE, EMBASE, PubMed, and China National Knowledge Infrastructure up to August 2023. The included trials reported the PNI assessment in adult population with critical illness and its predictive capacity for AKI. Data on study characteristics, subgroup covariates, and diagnostic performance of PNI, including sensitivity, specificity, and event rates, were extracted. A diagnostic test accuracy meta-analysis was performed. Subgroup analyses and meta-regression were utilized to investigate the sources of heterogeneity. The GRADE framework evaluated the confidence in the meta-analysis’s evidence. Results The analysis encompassed 16 studies with 17 separate cohorts, totaling 21,239 patients. The pooled sensitivity and specificity of PNI for AKI prediction were 0.67 (95% CI 0.58–0.74) and 0.74 (95% CI 0.67–0.80), respectively. The pooled positive likelihood ratio was 2.49 (95% CI 1.99–3.11; low certainty), and the negative likelihood ratio was 0.46 (95% CI 0.37–0.56; low certainty). The pooled diagnostic odds ratio was 5.54 (95% CI 3.80–8.07), with an area under curve of summary receiver operating characteristics of 0.76. Subgroup analysis showed that PNI’s sensitivity was higher in medical populations than in surgical populations (0.72 vs. 0.55; p

Immunosenescence refers to the immune system changes observed in individuals over 50 years old, characterized by diminished immune response and chronic inflammation. Recent investigations have highlighted similar immune alterations in patients with reduced kidney function. The immune system and kidney function have been found to be closely interconnected. Studies have shown that as kidney function declines, both innate and adaptive immunity are affected. Chronic kidney disease (CKD) patients exhibit decreased levels of naive and regular T cells, as well as naive and memory B cells, while memory T cell counts increase. Furthermore, research suggests that CKD and end-stage kidney disease (ESKD) patients experience early thymic dysfunction and heightened homeostatic proliferation of naive T cells. In addition to reduced thymic T cell production, CKD patients display shorter telomeres in both CD4+ and CD8+ T cells.Declining kidney function induces uremic conditions, which alter the intestinal metabolic environment and promote pathogen overgrowth while reducing diversity. This dysbiosis-driven imbalance in the gut microbiota can result in elevated production of uremic toxins, which, in turn, enter the systemic circulation due to compromised gut barrier function under uremic conditions. The accumulation of gut-derived uremic toxins exacerbates local and systemic kidney inflammation. Immune-mediated kidney damage occurs due to the activation of immune cells in the intestine as a consequence of dysbiosis, leading to the production of cytokines and soluble urokinase-type plasminogen activator receptor (suPAR), thereby contributing to kidney inflammation.In this review, we delve into the fundamental mechanisms of immunosenescence in CKD, encompassing alterations in adaptive immunity, gut dysbiosis, and an overview of the clinical findings pertaining to immunosenescence.

Background: The effectiveness and side effects between different medical treatments in patients with primary hyperaldosteronism have not been systematically studied. Objective: To analyze the efficacy between different mineralocorticoid receptor antagonists (MRAs) and epithelial sodium channel (ENaC) inhibitors in a network meta-analysis (NMA) framework, while also evaluating adverse events. Design: Systematic review and NMA. Data sources and methods: The systematic review and NMA was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, MEDLINE, the Cochrane library, and Excerpta Medica database (EMBASE) were searched for randomized controlled trials (RCTs) involving adult patients with primary hyperaldosteronism until 23 June 2023. Studies that compared the efficacy and side effects of different medical treatments of primary hyperaldosteronism were included. The primary outcomes included the effect on blood pressure, serum potassium, and major adverse cardiovascular events. The secondary outcomes were adverse events related to MRAs (hyperkalemia and gynecomastia). Frequentist NMA and pairwise meta-analysis were conducted. Results: A total of 5 RCTs comprising 392 participants were included. Eplerenone, esaxerenone, and amiloride were compared to spironolactone and demonstrated comparable effect on the reduction of systolic blood pressure. In comparison to spironolactone, eplerenone exhibited a less pronounced effect on reducing diastolic blood pressure [−4.63 mmHg; 95% confidence interval (CI): −8.87 to −0.40 mmHg] and correcting serum potassium (−0.2 mg/dL; 95% CI: −0.37 to −0.03 mg/dL). Spironolactone presented a higher risk of gynecomastia compared with eplerenone (relative risk: 4.69; 95% CI: 3.58–6.14). Conclusion: The present NMA indicated that the blood pressure reduction and potassium-correcting effects of the three MRAs may demonstrate marginal differences, with confidence levels in the evidence being very low. Therefore, further research is needed to explore the efficacy of these MRAs, especially regarding their impact on mortality and cardiovascular outcomes. Trial registration: PROSPERO (CRD: 42023446811).

IntroductionHypertriglyceridemia is the most prevalent dyslipidemia in patients with chronic kidney disease (CKD). However, research about fibrate treatment in CKD patients is limited, and assessing its benefits becomes challenging due to the frequent concurrent use of statins. Thus, this study is aimed to investigate the role of fibrate in CKD stage 3 patients with hypertriglyceridemia who did not receive other lipid-lowering agents.MethodsThis study enrolled patients newly diagnosed CKD3 with LDL-C200mg/dL but not receiving fibrate treatment). The inverse probability of treatment weighting was performed to balance baseline characteristics.ResultsCompared with the non-fibrate group (n=2020), the fibrate group (n=705) exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (MACCEs) (10.4% vs. 12.8%, hazard ratios [HRs]: 0.69, 95% confidence interval [CI]: 0.50 to 0.95), AMI (2.3% vs. 3.9%, HR: 0.52, 95% CI: 0.37 to 0.73), and ischemic stroke (6.3% vs. 8.0%, HR: 0.67, 95% CI: 0.52 to 0.85). The risk of all-cause mortality (5.1% vs. 4.5%, HR: 1.09, 95% CI: 0.67 to 1.79) and death from CV (2.8% vs. 2.3%, HR: 1.07, 95% CI: 0.29 to 2.33) did not significantly differ between the 2 groups.ConclusionThis study suggests that, in moderate CKD patients with hypertriglyceridemia but LDL-C < 100mg/dL who did not take other lipid-lowering agents, fibrates may be beneficial in reducing cardiovascular events.

Abstract With ageing populations, new elderly end-stage kidney disease (ESKD) cases rise. Unlike younger patients, elderly ESKD patients are less likely to undergo kidney transplant, and therefore the decision of receiving peritoneal dialysis (PD) and hemodialysis (HD) is more crucial. A total of 36,852 patients, aged more than 65, who were newly diagnosed with ESKD and initiated renal replacement therapy between 2013 and 2019 were identified. These patients were categorized into two groups: the PD group and the HD group according to their long-term renal replacement treatment. After propensity score matching, the PD group (n = 1628) displayed a lower incidence of major adverse cardiac and cerebrovascular events (MACCE) (10.09% vs. 13.03%, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.66–0.83), malignancy (1.23% vs. 2.14%, HR: 0.55, 95% CI: 0.40–0.76), and MACCE-associated mortality (1.35% vs. 2.25%, HR: 0.62, 95% CI: 0.46–0.84) compared to the HD group (n = 6512). However, the PD group demonstrated a higher rate of infection (34.09% vs. 24.14%, HR: 1.28, 95% CI: 1.20–1.37). The risks of all-cause mortality and infection-associated mortality were not different. This study may provide valuable clinical information to assist elderly ESKD patients to choose HD or PD as their renal replacement therapy.

Infective endocarditis (IE) is a serious infection and causes significant morbidity and mortality. However, the benefit of surgery for endocarditis besides antibiotic treatment in dialysis patients remains controversial. We performed a systematic review of studies published between 1960 and February 2022. Meta-analysis was conducted with a random-effects model to explore the in-hospital, 30, 60, 90, 180-d, and 1-year mortality rates in adult dialysis patients with IE. Sensitivity analysis, subgroup analysis, and meta-regression were performed to explore potential sources of heterogeneity. Confidence of evidence was evaluated by the GRADE system. Thirteen studies were included. The pooled odds ratio of in-hospital mortality was 0.62 (95% confidence interval [CI]: 0.30–1.28, p = .17), with moderate heterogeneity (I2 = 62%, p

Introduction: Acute kidney disease (AKD) represents a continuum of kidney injury for 7 to 90 days after acute kidney injury (AKI). The incidence and prognosis of AKD after acute decompensated heart failure (ADHF) are currently unclear. The aims of this study were to explore the incidence of AKD and the transition from AKI to AKD, to identify risk factors for AKD and develop a prediction model for any-stage AKD, and to evaluate the prognosis of AKD. Methods: A total of 7519 patients admitted for ADHF between January 1, 2008, and December 31, 2018, from a multi-institutional database were identified. The composite outcomes after ADHF were stage 3 AKD and all-cause death. The prognosis impact of AKD, including major adverse kidney events (MAKEs), all-cause death, and heart failure hospitalization (HFH), during 5 years of follow-up was analyzed. Results: The overall incidence of AKI and AKD after ADHF was 9% and 21.2%, respectively; 39.4% of the patients diagnosed with having AKI during ADHF subsequently developed AKD whereas 19.4% of the patients without an identified AKI episode subsequently developed AKD. The predictive scoring models revealed C-statistics of 0.726 (95% CI: 0.712–0.740) for any-stage AKD and 0.807 (95% CI: 0.793–0.821) for the composite of stage 3 AKD and death. Finally, AKD was associated with higher risks of all-cause death, MAKE, and HFH during the 5 years of follow-up (P < 0.001). Conclusion: AKD after ADHF are associated with adverse outcomes. Our model could help in identification of patients at risk for AKD development, especially in those who did not have an index AKI episode.

Abstract The outcomes of patients with incident kidney failure who start hemodialysis are influenced by several factors. Whether hemodialysis facility characteristics are associated with patient outcomes is unclear. We included adults diagnosed as having kidney failure requiring hemodialysis during January 1, 2001 to December 31, 2013 from the Taiwan National Health Insurance Research Database to perform this retrospective cohort study. The exposures included different sizes and levels of hemodialysis facilities. The outcomes were all-cause mortality, cardiovascular death, infection-related death, hospitalization, and kidney transplantation. During 2001–2013, we identified 74,406 patients and divided them in to three groups according to the facilities where they receive hemodialysis: medical center (n = 8263), non-center hospital (n = 40,008), and clinic (n = 26,135). The multivariable Cox model demonstrated that a larger facility size was associated with a low mortality risk (hazard ratio [HR] 0.991, 95% confidence interval [95% CI] 0.984–0.998; every 20 beds per facility). Compared with medical centers, patients in non-center hospitals and clinics had higher mortality risks (HR 1.13, 95% CI 1.09–1.17 and HR 1.11, 95% CI 1.06–1.15, respectively). Patients in medical centers and non-center hospitals had higher risk of hospitalization (subdistribution HR [SHR] 1.11, 95% CI 1.10–1.12 and SHR 1.22, 95% CI 1.21–1.23, respectively). Patients in medical centers had the highest rate of kidney transplantation among the three groups. In patients with incident kidney failure, a larger hemodialysis facility size was associated with lower mortality. Overall, medical center patients had a lower mortality rate and higher transplantation rate, whereas clinic patients had a lower hospitalization risk.

Background The benefit of low‐density lipoprotein cholesterol (LDL‐C) levels in chronic kidney disease populations remains unclear. This study evaluated the cardiovascular and renal outcomes in patients with stage 3 chronic kidney disease with different LDL‐C levels during statin treatment. Methods and Results There were 8500 patients newly diagnosed as having stage 3 chronic kidney disease under statin treatment who were identified from the Chang Gung Research Database and divided into 3 groups according to their first LDL‐C level after the index date: 100 mg/dL. Inverse probability of treatment weighting was performed to balance baseline characteristics. Compared with the LDL‐C ≥100 mg/dL group, the 70≤LDL‐C100 mg/dL. Moreover, the 70≤LDL‐C

ObjectsCardiac surgery is associated with acute kidney injury (AKI). However, the effects of various pharmacological and non-pharmacological strategies for AKI prevention have not been thoroughly investigated, and their effectiveness in preventing AKI-related adverse outcomes has not been systematically evaluated.MethodsStudies from PubMed, Embase, and Medline and registered trials from published through December 2021 that evaluated strategies for preventing post–cardiac surgery AKI were identified. The effectiveness of these strategies was assessed through a network meta-analysis (NMA). The secondary outcomes were prevention of dialysis-requiring AKI, mortality, intensive care unit (ICU) length of stay (LOS), and hospital LOS. The interventions were ranked using the P-score method. Confidence in the results of the NMA was assessed using the Confidence in NMA (CINeMA) framework.ResultsA total of 161 trials (involving 46,619 participants) and 53 strategies were identified. Eight pharmacological strategies {natriuretic peptides [odds ratio (OR): 0.30, 95% confidence interval (CI): 0.19–0.47], nitroprusside [OR: 0.29, 95% CI: 0.12–0.68], fenoldopam [OR: 0.36, 95% CI: 0.17–0.76], tolvaptan [OR: 0.35, 95% CI: 0.14–0.90], N-acetyl cysteine with carvedilol [OR: 0.37, 95% CI: 0.16–0.85], dexmedetomidine [OR: 0.49, 95% CI: 0.32–0.76;], levosimendan [OR: 0.56, 95% CI: 0.37–0.84], and erythropoietin [OR: 0.62, 95% CI: 0.41–0.94]} and one non-pharmacological intervention (remote ischemic preconditioning, OR: 0.76, 95% CI: 0.63–0.92) were associated with a lower incidence of post–cardiac surgery AKI with moderate to low confidence. Among these nine strategies, five (fenoldopam, erythropoietin, natriuretic peptides, levosimendan, and remote ischemic preconditioning) were associated with a shorter ICU LOS, and two (natriuretic peptides [OR: 0.30, 95% CI: 0.15–0.60] and levosimendan [OR: 0.68, 95% CI: 0.49–0.95]) were associated with a lower incidence of dialysis-requiring AKI. Natriuretic peptides were also associated with a lower risk of mortality (OR: 0.50, 95% CI: 0.29–0.86). The results of a sensitivity analysis support the robustness and effectiveness of natriuretic peptides and dexmedetomidine.ConclusionNine potentially effective strategies were identified. Natriuretic peptide therapy was the most effective pharmacological strategy, and remote ischemic preconditioning was the only effective non-pharmacological strategy. Preventive strategies might also help prevent AKI-related adverse outcomes. Additional studies are required to explore the optimal dosages and protocols for potentially effective AKI prevention strategies.

Risk and prognostic factors for acute kidney injury (AKI) have been published in various studies across various populations. We aimed to explore recent advancements in and provide updated recommendations on AKI risk stratification and information about local AKI risk factors. The Taiwan Acute Kidney Injury Task Force reviewed relevant recently published literature and reached a consensus after group meetings. Systemic review and group discussion were performed. We conducted a meta-analysis according to the PRISMA statement for evaluating the diagnostic performance of the furosemide stress test. Several risk and susceptibility factors were identified through literature review. Contrast-associated AKI prediction models after coronary angiography were one of the most discussed prediction models we found. The basic approach and evaluation of patients with AKI was also discussed. Our meta-analysis found that the furosemide stress test can be used as a prognostic tool for AKI progression and to identify patients with AKI who are at low risk of renal replacement therapy. Factors associated with de novo chronic kidney injury or renal non-recovery after AKI were identified and summarized. Our review provided practical information about early identification of patients at high risk of AKI or disease progression for Taiwan local clinics.

Abstract Acute kidney injury (AKI) is a common complication in acute heart failure (AHF) and is associated with prolonged hospitalization and increased mortality. The aim of this study was to externally validate existing prediction models of AKI in patients with AHF. Data for 10,364 patients hospitalized for acute heart failure between 2008 and 2018 were extracted from the Chang Gung Research Database and analysed. The primary outcome of interest was AKI, defined according to the KDIGO definition. The area under the receiver operating characteristic (AUC) curve was used to assess the discrimination performance of each prediction model. Five existing prediction models were externally validated, and the Forman risk score and the prediction model reported by Wang et al. showed the most favourable discrimination and calibration performance. The Forman risk score had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.696, 0.829, and 0.817, respectively. The Wang et al. model had AUCs for discriminating AKI, AKI stage 3, and dialysis within 7 days of 0.73, 0.858, and 0.845, respectively. The Forman risk score and the Wang et al. prediction model are simple and accurate tools for predicting AKI in patients with AHF.

A novel folded multi-pass cell consisting of three non-coaxial mirrors (spherical mirror or plane mirror) is proposed for laser spectroscopy. Three mirrors of the folded multi-pass cell can arrange in V-shape to form a stable non-coaxial multi-pass cell. Furthermore, in order to research the stability of the multi-pass cell under off-axis mirror’s astigmatism circumstance, an equivalent coaxial multi-pass cell and modified ABCD matrix model for the spot pattern of the folded multi-pass cell is proposed, by which a series of the detailed numerical calculations were implemented to analyze the optical path length of the multi-pass cell. Many spot patterns obtained with a high fill factor improve the utilization efficiency of the surface of the mirror and produce a longer total optical path length. The several typical types of folded multi-pass cells consisting of the different mirrors and base lengths were selected to demonstrate the cell’s self-consistent condition and power for a longer-optical path length. Three effective optical path lengths of 49.6, 97.6 and 173.6 m were obtained, respectively.

BackgroundAdvanced chronic kidney disease (CKD) patients are at higher risk of sepsis-related mortality following infection and bacteremia. Interestingly, the urate-lowering febuxostat and allopurinol, both xanthine oxidase inhibitors (XOis), have been suggested to influence the sepsis course in animal studies. In this study, we aim to investigate the relationship between XOis and infection/sepsis risk in pre-dialysis population.MethodsPre-dialysis stage 5 CKD patients with gout were identified through the National Health Insurance Research Database (NHIRD) in Taiwan from 2012 to 2016. Outcomes were also compared with national data.ResultsIn our nationwide, population-based cohort study, 12,786 eligible pre-dialysis stage 5 CKD patients were enrolled. Compared to non-users, febuxostat users and allopurinol users were associated with reduced sepsis/infection risk [hazard ratio (HR), 0.93; 95% confidence interval (CI), 0.87–0.99; P = 0.0324 vs. HR, 0.92; 95% CI, 0.86–0.99; P = 0.0163]. Significant sepsis/infection-related mortality risk reduction was associated with febuxostat use (HR, 0.68; 95% CI, 0.52–0.87). Subgroup analysis demonstrated preference of febuxostat over allopurinol in sepsis/infection-related mortality among patients younger than 65 years of age, stain users, non-steroidal anti-inflammatory drug non-users, and non-diabetics. There was no significant difference in major adverse cardiac and cerebrovascular event (MACCE) risk between users and non-users while reduced risk of all-cause mortality was observed for XOi users.ConclusionsUse of XOi in pre-dialysis stage 5 CKD patients may be associated with reduced risk of sepsis/infection and their related mortality without increased MACCE and overall mortality.

Much of the work in alpha NFT has focused on evaluating changes in alpha amplitude. However, the generation mechanism of training-induced alpha activity has not yet been clarified. The present study aimed to identify sources of training-induced alpha activity through four temporal/spectral analytic techniques, i.e., the max peak average (MPA), positive average (PA), negative average (NA) and event-related spectral perturbation average (ERSPA) methods. Thirty-five healthy participants were recruited into an alpha group receiving feedback of 8-12-Hz amplitudes, and twenty-eight healthy participants were recruited into a control group receiving feedback of random 4-Hz amplitudes from the range of 7 to 20 Hz. Twelve sessions were performed within 4 weeks (3 sessions per week). The control group had no change in the amplitude spectrum. In contrast, twenty-nine participants in the alpha group showed significant alpha amplitude increases exclusively and were identified as "responders". A whole-head EEG was recorded for the "responders" after NFT. The epochs of training-induced alpha activity from whole-head EEG were averaged by four different methods for equivalent current dipole source analysis. High agreement and Cohen's kappa coefficients on dipole source localization between each method were observed, showing that the dipole clusters of training-induced alpha activity were consistently located in the precuneus, posterior cingulate cortex (PCC) and middle temporal gyrus. The residual variance (goodness of fit) for dipole estimation of the MPA was significantly smaller than that of the others. Our findings indicate that the precuneus, PCC and middle temporal gyrus play important roles in enhancing training-induced alpha activity. The four averaging methods (especially the MPA method) were suitable for investigating sources of brainwaves. Additionally, three dipoles can be used for dipole source analysis of training-induced alpha activity in future research, especially the training sites are around the central regions.

Background. Various forms of theta-burst stimulation (TBS) such as intermittent TBS (iTBS) and continuous TBS (cTBS) have been introduced as novel facilitation/suppression schemes during repetitive transcranial magnetic stimulation (rTMS), demonstrating a better efficacy than conventional paradigms. Herein, we extended the rTMS-TBS schemes to electrical stimulation of high-definition montage (HD-TBS) and investigated its neural effects on the human brain. Methods. In a within-subject design, fifteen right-handed healthy adults randomly participated in 10 min and 2 mA HD-TBS sessions: unilateral (Uni)-iTBS, bilateral (Bi)-cTBS/iTBS, and sham stimulation over primary motor cortex regions. A 20-channel near-infrared spectroscopy (NIRS) system was covered on the bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal lobe (PL) for observing cerebral hemodynamic responses in the resting-state and during fast finger-tapping tasks at pre-, during, and poststimulation. Interhemispheric correlation coefficient (IHCC) and wavelet phase coherence (WPCO) from resting-state NIRS and concentration of oxyhemoglobin during fast finger-tapping tasks were explored to reflect the symmetry between the two hemispheres and cortical activity, respectively. Results. The IHCC and WPCO of NIRS data in the SMC region under Bi-cTBS/iTBS showed relatively small values at low-frequency bands III (0.06–0.15 Hz) and IV (0.02–0.06), indicating a significant desynchronization in both time and frequency domains. In addition, the SMC activation induced by fast finger-tapping exercise was significantly greater during Uni-iTBS as well as during and post Bi-cTBS/iTBS sessions. Conclusions. It appears that a 10 min and 2 mA Bi-cTBS/iTBS applied over two hemispheres within the primary motor cortex region could effectively modulate the interhemispheric synchronization and cortical activation in the SMC of healthy subjects. Our study demonstrated that bilateral HD-TBS approaches is an effective noninvasive brain stimulation scheme which could be a novel therapeutic for inducing effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.

Abstract Background The use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated. Results We identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74–0.87) and 0.88 (95% CI 0.82–0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96–7.50), the pooled negative LR was 0.26 (95% CI 0.19–0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00–51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72–0.91) and 0.77 (95% CI 0.64–0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06–4.86) and 0.25 (95% CI 0.14–0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74–32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1–2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51–13.33). Conclusion The FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.

Abstract Background The optimal timing of renal replacement therapy (RRT) initiation is debatable. Many articles in this field enrolled trials not based on acute kidney injury. The safety of the watchful waiting strategy has not been fully discussed, and late RRT initiation criteria vary across studies. The effect of early RRT initiation in the AKI population with high plasma neutrophil gelatinase-associated lipocalin (NGAL) has not been examined yet. Methods In accordance with PRISMA guidelines, the PubMed, Embase, and Cochrane databases were systemically searched for randomized controlled trials (RCTs). Trials not conducted in the AKI population were excluded. Data of study characteristics, primary outcome (all-cause mortality), and related secondary outcomes [mechanical ventilation (MV) days, length of hospital stay, RRT days, and length of ICU stay] were extracted. The outcomes were compared between early and late RRT groups by estimating the pooled odds ratio (OR) for binary outcomes and the weighted mean difference for continuous outcomes. Prospective trials were also examined and analyzed using the same method. Results Nine RCTs with 1938 patients were included. Early RRT did not provide a survival benefit (pooled OR, 0.88; 95% confidence interval [CI] 0.62–1.27). However, the early RRT group had significantly fewer MV days (pooled mean difference, − 3.98 days; 95% CI − 7.81 to − 0.15 days). Subgroup analysis showed that RCTs enrolling the surgical population (P = .001) and the AKI population with high plasma NGAL (P = .031) had favorable outcomes regarding RRT days in the early initiation group. Moreover, 6 of 9 RCTs were selected for examining the safety of the watchful waiting strategy, and no significant differences were found in primary and secondary outcomes between the early and late RRT groups. Conclusions Overall, early RRT initiation did not provide a survival benefit, but a possible benefit of fewer MV days was detected. Early RRT might also provide the benefit of shorter MV or RRT support in the surgical population and in AKI patients with high plasma NGAL. Depending on the conventional indication for RRT initiation, the watchful waiting strategy is safe on the basis of all primary and secondary outcomes.

Various infarct sizes induced by middle cerebral artery occlusion (MCAO) generate inconsistent outcomes for stroke preclinical study. Monitoring cerebral hemodynamics may help to verify the outcome of MCAO. The aim of this study was to investigate the changes in brain tissue optical properties by frequency-domain near-infrared spectroscopy (FD-NIRS), and establish the relationship between cerebral hemodynamics and infarct variation in MCAO model. The rats were undergone transient MCAO using intraluminal filament. The optical properties and hemodynamics were measured by placing the FD-NIRS probes on the scalp of the head before, during, and at various time-courses after MCAO. Bimodal infarction severities were observed after the same 90-min MCAO condition. Significant decreases in concentrations of oxygenated hemoglobin ([HbO]) and total hemoglobin ([HbT]), tissue oxygenation saturation (StO2), absorption coefficient (μa) at 830 nm, and reduced scattering coefficient (μs’) at both 690 and 830 nm were detected during the occlusion in the severe infarction but not the mild one. Of note, the significant increases in [HbO], [HbT], StO2, and μa at both 690 and 830 nm were found on day 3; and increases in μs’ at both 690 and 830 nm were found on day 2 and day 3 after MCAO, respectively. The interhemispheric correlation coefficient (IHCC) was computed from low-frequency hemodynamic oscillation of both hemispheres. Lower IHCCs standing for interhemispheric desynchronizations were found in both mild and severe infarction during occlusion, and only in severe infarction after reperfusion. Our finding supports that sequential FD-NIRS parameters may associated with the severity of the infarction in MCAO model, and the consequent pathologies such as vascular dysfunction and brain edema. Further study is required to validate the potential use of FD-NIRS as a monitor for MCAO verification.

Background: Rigid dietary controls and pill burden make a very-low protein (0.3–0.4 g/kg body weight per day), vegetarian diet supplemented with ketoanalogues of amino acids (sVLPD) hard to follow in the long-term. This study aimed to evaluate whether a ketoanalogue supplemental low-protein diet (sLPD) (0.6 g/kg body weight per day) could also reduce the risks of dialysis among CKD stage 4 patients. Methods: Patients aged >20 years with a diagnosis of stage 4 CKD who subsequently received ketosteril treatment, which is the most commonly used ketoanalogue of essential amino acids, between 2003 and 2018 were identified from the Chang Gung Research Database (CGRD). Then, these individuals were divided into two groups according to the continuation of ketosteril for more than three months or not. The primary outcome was ESKD requiring maintenance dialysis. Results: With one-year follow-up, the continuation group (n = 303) exhibited a significantly lower incidence of new-onset end-stage kidney disease (ESKD) requiring maintenance dialysis (6.8% vs. 10.4%, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41–0.94) in comparison to the discontinuation group (n = 238). Conclusions: This study demonstrated that initiating sLPDs since CKD stage 4 may additionally reduce the short-term risks of commencing dialysis without increasing CV events, infections, or mortality.

Background Dialysis‐requiring acute kidney injury (D‐AKI) is a major complication of cardiovascular surgery that results in worse prognosis. However, the incidence and impacts of D‐AKI in different types of cardiac surgeries have not been fully investigated. Methods and Results Patients admitted for cardiovascular surgery between July 1, 2004, and December 31, 2013, were identified from the National Health Insurance Research Database of Taiwan. The patients were grouped into D‐AKI (n=3089) and non–D‐AKI (n=42 151) groups. The outcome was all‐cause mortality and major adverse kidney event. The long‐term outcomes were worse in the D‐AKI group than the non–D‐AKI group (hazard ratio [HR], 3.89; 95% CI, 3.79–3.99 for major adverse kidney event; HR, 2.89; 95% CI, 2.81–2.98 for all‐cause mortality). Patients who underwent aortic surgery had higher risk for D‐AKI than other types of surgeries, but they were also more likely to recover. The long‐term dialysis rate for the patients who recovered from D‐AKI was also lowest in those who underwent aortic surgery. Among all types of cardiac surgeries with D‐AKI, patients who had heart valve surgery exhibited the greatest risks of all‐cause mortality (HR, 6.04; 95% CI, 5.78–6.32). Conclusions Compared with other heart surgeries, aortic surgery resulted in a higher incidence of D‐AKI but better renal recovery, better short‐term outcome, and lower incidences of long‐term dialysis.

BackgroundIt has been a matter of much debate whether the co-administration of furosemide and albumin can achieve better diuresis and natriuresis than furosemide treatment alone. There is inconsistency in published trials regarding the effect of this combination therapy. We, therefore, conducted this meta-analysis to explore the efficacy of furosemide and albumin co-administration and the factors potentially influencing the diuretic effect of such co-administration.MethodsIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, Medline, and Cochrane databases. Prospective studies with adult populations which comparing the effect of furosemide and albumin co-administration with furosemide alone were included. The outcomes including diuretic effect and natriuresis effect measured by hourly urine output and hourly urine sodium excretion from both groups were extracted. Random effect model was applied for conducting meta-analysis. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity of treatment effects.ResultsBy including 13 studies with 422 participants, the meta-analysis revealed that furosemide with albumin co-administration increased urine output by 31.45 ml/hour and increased urine excretion by 1.76 mEq/hour in comparison to furosemide treatment alone. The diuretic effect of albumin and furosemide co-administration was better in participants with low baseline serum albumin levels (< 2.5 g/dL) and high prescribed albumin infusion doses (> 30 g), and the effect was more significant within 12 hours after administration. Diuretic effect of co-administration was better in those with baseline Cr > 1.2 mg/dL and natriuresis effect of co-administration was better in those with baseline eGFR < 60 ml/min/1.73m2.ConclusionCo-administration of furosemide with albumin might enhance diuresis and natriuresis effects than furosemide treatment alone but with high heterogeneity in treatment response. According to the present meta-analysis, combination therapy might provide advantages compared to the furosemide therapy alone in patients with baseline albumin levels lower than 2.5 g/dL or in patients receiving higher albumin infusion doses or in patients with impaired renal function. Owing to high heterogeneity and limited enrolled participants, further parallel randomized controlled trials are warranted to examine our outcome.RegistrationPROSEPRO ID: CRD42020211002; https://clinicaltrials.gov/.

The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19−23%), an intensive care unit admission rate of 26% (95% CI: 22–31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62–81%), an acute kidney injury rate of 44% (95% CI: 39–49%), a kidney replacement therapy rate of 12% (95% CI: 9–15%), and a graft loss rate of 8% (95% CI: 5–15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.

Acute kidney injury (AKI) is a common complication of hospitalization that greatly and negatively affects the short-term and long-term outcomes of patients. Current guidelines use serum creatinine level and urine output rate for defining AKI and as the staging criteria of AKI. However, because they are not sensitive or specific markers of AKI, clinicians find it difficult to predict the occurrence of AKI and prescribe timely treatment. Advances in computing technology have led to the recent use of machine learning and artificial intelligence in AKI prediction, recent research reported that by using electronic health records (EHR) the AKI prediction via machine-learning models can reach AUROC over 0.80, in some studies even reach 0.93. Our review begins with the background and history of the definition of AKI, and the evolution of AKI risk factors and prediction models is also appraised. Then, we summarize the current evidence regarding the application of e-alert systems and machine-learning models in AKI prediction.

BackgroundThis study analyzed the survival and protective predictors of in-hospital cardiopulmonary cerebral resuscitation (CPCR) to potentially help physicians create effective treatment plans for End-stage kidney disease (ESKD) patients.MethodsWe extracted the data of 7,116 ESKD patients who received their first in-hospital CPCR after initial dialysis between 2004 and 2012 from the National Health Insurance Research Database. The primary outcome was the survival rate during the first in-hospital CPCR. The secondary outcome was the median post-discharge survival.ResultsFrom 2004 through 2012, the incidence of in-hospital CPCR decreases from 3.97 to 3.67 events per 1,000 admission days (P for linear trend ConclusionThe incidence of in-hospital CPCR and the duration post-discharge among ESKD patients improved despite there being no significant difference in the survival rate of ESKD patients after CPCP. Either ICD or CRT-D implantation may be advisable for ESKD patients with a high risk of sudden cardiac death.

Background: Among critical patients, few studies have evaluated the discrimination of current illness scoring systems in predicting outcomes after continuous renal replacement therapy (CRRT) initiation. Methods: Patients receiving CRRT in the ICU between 2005 and 2018 from the Chang Gung Research Database were extracted. All the components of the Acute Physiology Assessment and Chronic Health Evaluation (APACHE) III, Sequential Organ Failure Assessment (SOFA), qSOFA, and MOSAIC scoring systems on days 1, 3, and 7 of CRRT were recorded. Patients older than 80 years were identified and analyzed separately. Results: We identified 3370 adult patients for analysis. The discrimination ability of the scoring systems was acceptable at day 7 after CRRT initiation, including SOFA (area under the receiver operating characteristic curve, 74.1% (95% confidence interval, 71.7–76.5%)), APACHEIII (74.7% (72.3–77.1%)), and MOSAIC (71.3% (68.8%–73.9%)). These systems were not ideal on days 1 and 3, and that of qSOFA was poor at any time point. The discrimination performance was slightly better among patients ≥80 years. Conclusions: APACHE III, MOSAIC, and SOFA can be intensivists and families’ reference to make their decision of withdrawing or withholding CRRT after a short period of treatment, especially in adults ≥80 years old.

Acute kidney disease (AKD) is the persistence of renal injury between days 8 and 90 after an initial acute kidney injury (AKI). In this study, we aimed to explore the incidence of AKD, the association between AKD, and patient outcomes after acute type A aortic dissection (type A AAD) surgery. We identified 696 participants who underwent type A AAD surgery. Patients were categorized into stages 1 to 3 or 0 (non-AKD) AKD groups. Outcomes included major adverse kidney events (MAKEs), respiratory failure, all-cause readmission, and ischemic stroke from day 91 after operation. A total of 376 (54%) participants developed AKI, and 135/376 (35.9%) developed AKD. Moreover, 34/320 (10.6%) patients without AKI still developed AKD. Overall, 169/696 (24.3%) participants developed AKD. Patients with stages 2 and 3 AKD are associated with persisted declined renal function within 1 year. AKD was associated with a higher risk of MAKEs (hazard ratio (HR): 2.52, 95% confidence interval (CI) 1.90–3.33) and all-cause readmission (HR: 2.86, 95% CI: 2.10–3.89). Development of AKD with or without AKI is associated with a higher risk of MAKEs and hospitalization after acute aortic dissection surgery. Higher-stage AKD is associated with a trend of persistent decline in kidney function.

The relationship between hyperuricemia, gout, and renal disease has been investigated for several years. From the beginning, kidney disease has been considered a complication of gout; however, the viewpoints changed, claiming that hypertension and elevated uric acid (UA) levels are caused by decreased urate excretion in patients with renal impairment. To date, several examples of evidence support the role of hyperuricemia in cardiovascular or renal diseases. Several mechanisms have been identified that explain the relationship between hyperuricemia and chronic kidney disease, including the crystal effect, renin–angiotensin–aldosterone system activation, nitric oxide synthesis inhibition, and intracellular oxidative stress stimulation, and urate-lowering therapy (ULT) has been proven to reduce renal disease progression in the past few years. In this comprehensive review, the source and physiology of UA are introduced, and the mechanisms that explain the reciprocal relationship between hyperuricemia and kidney disease are reviewed. Lastly, current evidence supporting the use of ULT to postpone renal disease progression in patients with hyperuricemia and gout are summarized.

Urinary liver-type fatty acid binding protein (L-FABP) is a novel biomarker with promising performance in detecting kidney injury. Previous studies reported that L-FABP showed moderate discrimination in patients that underwent cardiac surgery, and other studies revealed that longer duration of cardiopulmonary bypass (CPB) was associated with a higher risk of postoperative acute kidney injury (AKI). This study aims to examine assessing CPB duration first, then examining L-FABP can improve the discriminatory ability of L-FABP in postoperative AKI. A total of 144 patients who received cardiovascular surgery were enrolled. Urinary L-FABP levels were examined at 4 to 6 and 16 to 18 h postoperatively. In the whole study population, the AUROC of urinary L-FABP in predicting postoperative AKI within 7 days was 0.720 at 16 to 18 h postoperatively. By assessing patients according to CPB duration, the urinary L-FABP at 16 to 18 h showed more favorable discriminating ability with AUROC of 0.742. Urinary L-FABP exhibited good performance in discriminating the onset of AKI within 7 days after cardiovascular surgery. Assessing postoperative risk of AKI through CPB duration first and then using urinary L-FABP examination can provide more accurate and satisfactory performance in predicting postoperative AKI.

We investigated the muscle alterations related to spasticity in stroke quantitatively using a portable manual spasticity evaluator.Methods: Quantitative neuro-mechanical evaluations under controlled passive elbow stretches in stroke survivors and healthy controls were performed in a research laboratory of a rehabilitation hospital. Twelve stroke survivors and nine healthy controls participated in the study. Spasticity and catch angle were evaluated at 90°/s and 270°/s with the velocities controlled through real-time audiovisual feedback. The elbow range of motion (ROM), stiffness, and energy loss were determined at a slow velocity of 30°/s. Four-dimensional measures including joint position, torque, velocity and torque change rate were analyzed jointly to determine the catch angle.Results: The catch angle was dependent on the stretch velocity and occurred significantly later with increasing velocity (p < 0.001), indicating position dependence of spasticity. The higher resistance felt by the examiner at the higher velocity was also due to more extreme joint position (joint angle) since the spastic joint was moved significantly further to a stiffer elbow position with the higher velocity. Stroke survivors showed smaller ROM (p < 0.001), higher stiffness (p < 0.001), and larger energy loss (p = 0.005). Compared to the controls, stroke survivors showed increased reflex excitability with higher reflex-mediated torque (p < 0.001) and at higher velocities (p = 0.02).Conclusion: Velocity dependence of spasticity is partially due to joint angle position dependence with the joint moved further (to a stiffer position where higher resistance was felt) at a higher velocity. The “4-dimensional characterization” including the joint angle, velocity, torque, and torque change rate provides a systematic tool to characterize catch angle and spasticity quantitatively.

For a long time, cisplatin-based chemotherapy had been viewed as first-line chemotherapy for advanced and metastatic urothelial carcinoma (UC). However, many patients with UC had been classified as cisplatin-ineligible who can only receive alternative chemotherapy with poor treatment response, and the vast majority of the cisplatin-eligible patients eventually progressed, even those with objective response with cisplatin-based chemotherapy initially. By understanding tumor immunology in UC, immune checkpoint inhibitors, targeting on programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) pathways, had been proven as first-line treatment for cisplatin-ineligible metastatic UC and as second-line treatment for patients with platinum-refractory metastatic UC by the U.S Food and Drug Administration (FDA). In 2020, JAVEIN bladder 100 further reported that PD-L1 inhibitors showed benefits on prolonged survival and progression-free survival as maintenance therapy. Besides targeting on immune checkpoint, manipulation of the tumor microenvironment by metabolic pathways intervention, including inhibition on tumor glycolysis, lactate accumulation and exogenous glutamine uptake, had been investigated in the past few years. In this comprehensive review, we start by introducing traditional chemotherapy of UC, and then we summarize current evidences supporting the use of immune checkpoint inhibitors and highlight ongoing clinical trials. Lastly, we reviewed the tumor metabolic characteristic and the anti-tumor treatments targeting on metabolic pathways.

Background: Previous studies have demonstrated that dietary therapy can delay the initiation of dialysis, but little research has investigated whether patients with very poor renal function would benefit from a dietary therapy. Methods: This study was performed by using the Chang Gung Research Database (CGRD), which is based on the largest medical system in Taiwan. Patients with estimated glomerular filtration rates (eGFR) < 15 mL/min/1.73 m2 between 2001 and 2015 with more than 3 months of low-protein diet supplemented with ketoanalogues (sLPD) were extracted (Ketosteril group). We then assigned five patients without any sLPD to match one patient of the Ketosteril group (comparison group). Both groups were followed up for 1 year for the initiation of dialysis and rates of major adverse cardiac and cerebrovascular events (MACCEs). Results: The Ketosteril group (n = 547), compared with the comparison group (n = 2735), exhibited a lower incidence of new-onset dialysis (40.2% vs. 44.4%, subdistribution hazard ratio (SHR): 0.80, 95% confidence interval (CI): 0.70–0.91) and MACCEs (3.7% vs. 5.9%, HR: 0.61, 95% CI: 0.38–0.97). The beneficial effect of an sLPD did not differ in patients with a baseline eGFR < 5 mL/min/1.73 m2. Conclusion: Even among patients with extremely low eGFR, sLPD treatment can safely delay the need for dialysis.

Background: Urinary calprotectin is a novel biomarker that distinguishes between intrinsic or prerenal acute kidney injury (AKI) in different studies. However, these studies were based on different populations and different AKI criteria. We evaluated the diagnostic accuracy of urinary calprotectin and compared its diagnostic performance in different AKI criteria and study populations. Method: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed, Embase, and the Cochrane database up to September 2018. The diagnostic performance of urinary calprotectin (sensitivity, specificity, predictive ratio, and cutoff point) was extracted and evaluated. Result: This study included six studies with a total of 502 patients. The pooled sensitivity and specificity were 0.90 and 0.93, respectively. The pooled positive likelihood ratio (LR) was 15.15, and the negative LR was 0.11. The symmetric summary receiver operating characteristic (symmetric SROC) with pooled diagnostic accuracy was 0.9667. The relative diagnostic odds ratio (RDOC) of the adult to pediatric population and RDOCs of different acute kidney injury criteria showed no significant difference in their diagnostic accuracy. Conclusion: Urinary calprotectin is a good diagnostic tool for the discrimination of intrinsic and prerenal AKI under careful inspection after exclusion of urinary tract infection and urogenital malignancies. Its performance is not affected by different AKI criteria and adult or pediatric populations.

OBJECTIVES: This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis. DATA SOURCES: We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions. STUDY SELECTION: Only randomized controlled trials (RCTs) were selected. DATA EXTRACTION: The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement. DATA SYNTHESIS: We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57–0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42–0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy. CONCLUSIONS: Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification. [ABSTRACT FROM AUTHOR]