Background: Proenkephalin A 119-159 (PENK) is freely filtered in the glomerulus with plasma levels correlating with glomerular filtration rate. Therefore, PENK has been proposed as an early indicator of acute kidney injury (AKI) although its performance is dependent on the clinical setting. This meta-analysis aimed to investigate the correlation between PENK levels and the development of AKI. Methods: We conducted a comprehensive search on the PubMed, Embase, Cochrane databases, the website ClinicalTrials.gov and Cnki.net until June 26, 2023. Summary receiver operating characteristic (SROC) curves were used to amalgamate the overall test performance. Diagnostic odds ratio (DOR) was employed to compare the diagnostic accuracy of PENK with other biomarkers. Quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. Results: We incorporated 11 observational studies with 3969 patients with an incidence of AKI of 23.4% (929 out of 3969 patients) with the best optimal cutoff value of PENK for early detection of AKI being 57.3 pmol/L. The overall sensitivity and specificity of PENK in identifying AKI were 0.69 (95% CI 0.62–0.75) and 0.76 (95% CI 0.68–0.82), respectively. The combined positive likelihood ratio (LR) stood at 2.83 (95% CI 2.06–3.88), and the negative LR was 0.41 (95% CI 0.33–0.52). The SROC curve showcased pooled diagnostic accuracy of 0.77 (95% CI 0.73–0.81). Interestingly, patients with a history of hypertension or heart failure demonstrated a lower specificity of PENK in correlating the development of AKI. Conclusion: Our results indicate that PENK possesses significant potential as a biomarker for the early detection of the development of AKI, using a cutoff point of 57.3 pmol/L for PENK.

For two-pattern at-speed scan testing, the excessive power supply noise at the launch cycle may cause the circuit under test to malfunction, leading to yield loss. This paper proposes a new weight assignment scheme for logic switching activity; it enhances the IR-drop assessment capability of the existing weighted switching activity (WSA) model. By including the power grid network structure information, the proposed weight assignment better reflects the regional IR-drop impact of each switching event. For ATPG, such comprehensive information is crucial in determining whether a switching event burdens the IR-drop effect. Simulation results show that, compared with previous weight assignment schemes, the estimated regional IR-drop profiles better correlate with those generated by commercial tools.

Metabolism dysregulation and protein energy wasting occur in patients with chronic kidney disease (CKD) and are associated with poor survival, especially in patients prior to starting dialysis. Accumulating evidence indicates that dietary supplementation with ketoanalogues (KAs, a mixture of branched-chain amino acids) exerts a variety of beneficial effects for patients with CKD. However, the role of KAs in diabetic kidney disease (DKD), one of the major causes of CKD, is still controversial. The aim of this study was to explore the impact of KA supplements on survival in patients with stage 5 DKD who have not yet started dialysis (DKD-5-ND). We analyzed a nationwide cohort retrieved from the National Health Insurance Research Database in Taiwan to study the long-term impact of KA supplements in patients with DKD-5-ND. We enrolled 15,782 incident pre-dialysis DKD patients between January 1, 2004 and December 31, 2007. Landmark analysis was used to eliminate immortal bias, and overlap weighting was used to balance differences between the KA users and nonusers in the beginning. The primary study endpoint was all-cause mortality, and the occurrence of permanent dialysis (presenting the end-stage renal disease, ESRD) and major adverse cardiovascular events (MACEs) was also evaluated. All patients were followed for five years or until death. The prevalence of KA usage in the DKD-5-ND patients was 6.3%. The 5-year all-cause mortality rate in the KA users was lower than that in the nonusers (34.7% vs 42.7%). After adjusting for known covariates, the KA users still had a lower risk of mortality (adjusted hazard ratio [aHR]: 0.73, 95% confidence interval [CI]: 0.66-0.82). In addition, the incidence of ESRD was also slightly lower among the KA users (90.9% for users vs 91.2% for nonusers, adjusted cause-specific hazard ratio [aCSHR]: 0.65, 95% CI: 0.61-0.69), and the occurrence of MACEs was lower (adjusted incidence rate ratios [aIRR]: 0.76, 95% CI: 0.67-0.86). Although the all-cause mortality was higher among patientsolder than 70 years (60.5% for KA users vs 46.5% for nonusers) the risk reduction seemed prominent among older patients (aHR: 0.65, 95% CI: 0.56-0.76 for patients aged ≥70 years; aHR: 0.82, 95% CI: 0.71-0.96 for patients aged < 70 years). The reduction in risks of mortality was consistent in subgroup analysis and sensitivity tests. The use of KA supplements seemed to be beneficial for patients with DKD-5-ND; further in-depth analysis of using KA for these patients is warranted.

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI.

Background: Urinary C–C motif chemokine ligand 14 (CCL14) has been described as an effective marker for delayed recovery of acute kidney injury (AKI), yet its efficacy has been found to vary between different trials. The goal of this research was to assess the predictive performance of urinary CCL14 as a marker for persistent AKI. 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 April 2023 for studies of adults (> 18 years) that reported the diagnostic performance of urinary CCL14. The sensitivity, specificity, number of events, true positive, and false positive results were extracted and evaluated. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. Results: We included six studies with 952 patients in this meta-analysis. The occurrence of persistent AKI among these patients was 39.6% (377/952). The pooled sensitivity and specificity results of urinary CCL14 in predicting persistent AKI were 0.81 (95% CI 0.72–0.87) and 0.71 (95% CI 0.53–0.84), respectively. The pooled positive likelihood ratio (LR) was 2.75 (95% CI 1.63–4.66), and the negative LR was 0.27 (95% CI 0.18–0.41). The HSROC with pooled diagnostic accuracy was 0.84. Conclusion: Our results suggest that urinary CCL14 can be used as an effective marker for predicting persistent AKI.

Background: Lysine demethylase 4C (KDM4C) is a nuclear protein that is essential for histone modification and acts as an important regulator of several transcription factors. Previous studies have shown that KDM4C may also play a role in mediating stress responses. The purpose of this study was to examine the roles of KDM4C in kidney development and acute kidney injury (AKI). Methods: The effect of KDM4C on kidney development was assessed by comparing the kidney phenotype between 96 zebrafish embryos treated with kdm4c-morpholino oligonucleotide and 96 untreated zebrafish embryos. We further examined whether KDM4C is essential for maintaining cell survival in AKI. Cultured human renal tubular cells were used for the in vitro study. Wild-type and Kdm4c knockout mice (C57BL/6NTac-Kdm4ctm1a(KOMP)Wtsi) were divided into a sham group and model group, and then subjected to ischemic reperfusion kidney injury (IRI-AKI). Blood samples and kidneys were collected at different time points (day 3, day 7, day 14, and day 28) and were processed for in vivo studies (n = 8 in each group). Results: Kdm4c knockdown significantly decreased zebrafish embryo survival and impaired kidney development. The in vitro study showed that KDM4C inhibition by JIB04 significantly increased cellular apoptosis under oxidative stress conditions. KDM4C knockdown cells had impaired autophagy function under stress conditions. The IRI-AKI mice study showed that KDM4C protein levels dynamically changed and were significantly correlated with HIF-1α levels in AKI. Kdm4c^−/− mice had significantly more severe renal impairment and increased kidney fibrosis than the wild-type mice. Cytokine array results also indicated that the kidneys of Kdm4c^−/− mice had increased inflammation in AKI compared with the wild-type mice. Further RNA sequence analysis revealed that KDM4C may regulate transcription factors related to mitochondrial dynamics and function. Conclusions: Our study suggests that KDM4C may play a critical role in regulating mitochondria, which is related to a protective effect on maintaining cell survival in AKI.