Comparison of the profiles of patients defined by age-adapted and fixed threshold CKD criteria: a nationwide, cross-sectional study.

Background: Kidney function declines naturally with advancing age. Therefore an age-adapted estimated glomerular filtration rate (eGFR) threshold has been proposed instead of the fixed threshold for CKD definition. This study aims to describe and compare the profile of CKD patients defined by these two criteria in a Chinese population. Method: We recruited adult participants with selected biochemical tests from the Chinese Physiological Constant and Health Condition survey conducted from 2007 to 2011, with the GFR estimated by the Chronic Kidney Disease Epidemiology Collaboration formula. The age-adapted threshold of eGFR is 75, 60 and 45 ml/min/1.73 m2 for the population <40 years of age, 40-64 years and >64 years, respectively. The fixed threshold is 60 ml/min/1.73 m2 for all ages. Results: Among the recruited 23 438 participants, 480 were diagnosed with CKD by fixed threshold criteria, while 391 were diagnosed with CKD by age-adapted criteria. Patients diagnosed by fixed threshold criteria were significantly older (66.4 versus 43.4 years; P < .001) and had a higher prevalence of all CVD risk factors compared with the non-CKD population. In contrast, age-adapted criteria defined a younger patient group and were not significantly associated with diabetes or obesity. When adjusted by age and gender, fixed threshold-defined CKD was not significantly associated with the number of coexisting CVD risk factors, while age-adapted-defined CKD was significantly associated. We also found that the CKD patients defined by age-adapted criteria matched well with the 2.5th percentile of eGFR in Chinese individuals. When compared with their age- and gender-matched controls, patients included by age-adapted criteria but excluded by fixed threshold criteria had a significantly higher prevalence of hypertension (23.2% versus 7.7%; P < .001) and hyperuricaemia (25.0% versus 5.5%; P < .001), while patients included only by the fixed threshold criteria were not significantly different in the prevalence of CVD risk factors and CKD-related disturbance except for hyperuricaemia (41.2% versus 14.0%; P < .001). Conclusion: An age-adapted criterion is more closely associated with CVD risk factors and CKD-related diseases compared with fixed threshold criteria.

Identification of biomarkers, immune infiltration landscape, and treatment targets of ischemia-reperfusion acute kidney injury at an early stage by bioinformatics methods.

BACKGROUND: Mechanisms underlying ischemia/reperfusion injury-acute kidney injury (IRI-AKI) are not fully elucidated. We conducted an integrative analysis of IRI-AKI by bioinformatics methods. METHODS: We screened gene expression profiles of the IRI-AKI at early phase from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene set enrichment analysis (GSEA). Immune cell infiltration analysis was performed to reveal the change of the microenvironment cell types. We constructed protein-protein interaction (PPI), and Cytoscape with plug-ins to find hub genes and modules. We performed robust rank aggregation (RRA) to combine DEGs and analyzed the target genes for miRNA/transcription factor (TF) and drug-gene interaction networks. RESULTS: A total of 239 and 384 DEGs were identified in GSE87024 and GSE34351 separately, with the 73 common DEGs. Enrichment analysis revealed that the significant pathways involve mitogen-activated protein kinase (MAPK) signaling, interleukin-17, and tumor necrosis factor (TNF) signaling pathway, etc. RRA analysis detected a total of 27 common DEGs. Immune cell infiltration analysis showed the plasma cells reduced and T cells increased in IRI-AKI. We identified JUN, ATF3, FOS, EGR1, HMOX1, DDIT3, JUNB, NFKBIZ, PPP1R15A, CXCL1, ATF4, and HSPA1B as hub genes. The target genes interacted with 23 miRNAs and 116 drugs or molecular compounds such as curcumin, staurosporine, and deferoxamine. CONCLUSION: Our study first focused on the early IRI-AKI adopting RRA analysis to combine DEGs in different datasets. We identified significant biomarkers and crucial pathways involved in IRI-AKI and first construct the immune landscape and detected the potential therapeutic targets of the IRI-AKI by drug-gene network.

Decreased urinary uromodulin is potentially associated with acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Urinary uromodulin (uUMOD) is one of the novel biomarkers for predicting AKI. However, currently available publications showed inconsistent results. We designed this meta-analysis to evaluate the potential association between uUMOD and AKI. METHODS: We searched research articles with no language restriction in Medline, Web of Science, Cochrane Library, Embase, and 3 Chinese datasets from inception to February 2021. We used random-effects models to estimate the standardized mean difference (SMD) between patients with AKI or not, while the leave-one-out method and random-effects meta-regression to evaluate the sensitivity and the impact of potential confounders such as age and surgery. RESULTS: The meta-analysis comprising 3148 subjects from 11 studies showed that the uUMOD of the AKI group is significantly lower than the non-AKI group (SMD: - 0.71; 95% confidence interval (CI), - 1.00, - 0.42, P < 0. 001, I2 = 78.8%). Subgroup analysis revealed the difference is also significant in a different age, surgery condition, and assay time but not acute rejection (AR) group, especially in children (SMD: - 1.21, 95% CI: - 1.80, - 0.61; P < 0.001) and patients undergoing surgery (SMD: - 1.03, 95% CI: - 1.75, - 0.30; P < 0.001). Lower uromodulin is associated with higher odds for AKI incidence (odds ratio = 2.47, 95% CI: 1.12, 5.47; P < 0.001, I2 = 89%). Meta-reggression found that age was associated with the SMD of uUMOD. The study outcome was reliably confirmed by the sensitivity analysis. CONCLUSION: The present study suggested a negative association between uUMOD and AKI especially in children and surgical patients.

Identification of the candidate lncRNA biomarkers for acute kidney injury: a systematic review and meta-analysis.

Background: This meta-analysis aims to summarize the studies of lncRNAs dysregulation in individual acute kidney injury (AKI) and identify the potential lncRNA biomarkers of AKI.Research design and methods: We systematically searched four databases to identify the lncRNA expression studies of AKI in animal models and patients. The lncRNAs expression data were extracted from 38 included studies, and lncRNA vote-counting strategy was applied to identify significant lncRNA biomarkers. The predicted targets of lncRNA biomarkers were obtained by searching Co-LncRNA, RBPmap, and LncBase v.2. Further, GO enrichment analysis and KEGG pathway analysis were performed.Results: We recognized a significant lncRNA signature of 21 up-regulated and 11 down-regulated lncRNAs, among which TapSAKI, XIST, MALAT1, CASC2, and HOXA-AS2 were dysregulated both in AKI rodent models and patients. About 28.0% of these lncRNAs mainly exist in the nucleus, which was also the most enriched GO cellular components term. The most relevant GO terms in biological process and molecular function associated with these lncRNAs were splicing, processing, and binding of mRNA.Conclusions: The present meta-analysis identified 31 significant dysregulated lncRNAs from 38 studies. TapSAKI, XIST, MALAT1, CASC2, and HOXA-AS2 were considered as the potential predictive biomarkers and therapeutic targets of AKI.

Bridging "Office-Based Care" With the "Virtual Practice Care Model": Evolving Care for Chronic Kidney Disease Patients in the COVID-19 Pandemic-And Beyond.

Since the outbreak of the coronavirus epidemic, the "virtual" telemedicine has become a critical substitute for patient-provider interactions. However, virtual encounters often face challenges in the care of patients in high-risk categories such as chronic kidney disease (CKD) patients. In this study, we explore the patient's satisfaction and the practical effects of a newly established telemedicine program on CKD patients' care during the COVID-19 pandemic. Based on a prior version of an online patient care platform established in 2017, we developed a customized and improved online telemedicine program designed to specifically address the challenges emerging from the pandemic. This included an online, smart phone-based strategy for triage and medical care delivery and psychological support. We invited a total of 278 CKD patients to join the new platform during the pandemic. The subjects in group A were patients utilizing our old online CKD system and were historical users registered at least 3 months before the pandemic. A pilot survey interrogating medical and psychological conditions was conducted. Feedback on the program as well as a psychological assessment were collected after 1 month. In total, 181 patients showed active responses to the program, with 289 person-time medical consultations occurring during the study. The virtual care program provided a rapid triage for 17% (30 out of 181) patients, with timely referral to in-patient medical encounters for their worsening medical conditions or severe psychological problems. Nearly all patients (97.4%) believed the program was helpful. The number of symptoms (OR 1.309, 95%CI 1.113-1.541; P = 0.001) and being enrolled during the pandemic (OR 3.939, 95% CI 1.174-13.221; P = 0.026) were associated with high stress. During the follow-up, the high-stress CKD group at baseline showed a significant decrease in avoidance score (6.9 ± 4.7 vs. 9.8 ± 1.9, P = 0.015). In conclusion, during the pandemic, we established an online telemedicine care program for CKD patients that provides a rapid triage function, effective CKD disease management, and potentially essential psychological support.