RESUMEN
BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN. METHODS: The gene chip data were retrieved from the GEO database using the search term ' diabetic nephropathy '. The ' limma ' software package was used to identify differentially expressed genes (DEGs) between DN and control samples. Gene set enrichment analysis (GSEA) was performed on genes obtained from the molecular characteristic database (MSigDB. The R package 'WGCNA' was used to identify gene modules associated with tubulointerstitial injury in DN, and it was crossed with immune-related DEGs to identify target genes. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on differentially expressed genes using the 'ClusterProfiler' software package in R. Three methods, least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE) and random forest (RF), were used to select immune-related biomarkers for diagnosis. We retrieved the tubulointerstitial dataset from the Nephroseq database to construct an external validation dataset. Unsupervised clustering analysis of the expression levels of immune-related biomarkers was performed using the 'ConsensusClusterPlus 'R software package. The urine of patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2021 to March 2023 was collected, and Elisa was used to detect the mRNA expression level of immune-related biomarkers in urine. Pearson correlation analysis was used to detect the effect of immune-related biomarker expression on renal function in DN patients. RESULTS: Four microarray datasets from the GEO database are included in the analysis : GSE30122, GSE47185, GSE99340 and GSE104954. These datasets included 63 DN patients and 55 healthy controls. A total of 9415 genes were detected in the data set. We found 153 differentially expressed immune-related genes, of which 112 genes were up-regulated, 41 genes were down-regulated, and 119 overlapping genes were identified. GO analysis showed that they were involved in various biological processes including leukocyte-mediated immunity. KEGG analysis showed that these target genes were mainly involved in the formation of phagosomes in Staphylococcus aureus infection. Among these 119 overlapping genes, machine learning results identified AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1 and FSTL1 as potential tubulointerstitial immune-related biomarkers. External validation suggested that the above markers showed diagnostic efficacy in distinguishing DN patients from healthy controls. Clinical studies have shown that the expression of AGR2, CX3CR1 and FSTL1 in urine samples of DN patients is negatively correlated with GFR, the expression of CX3CR1 and FSTL1 in urine samples of DN is positively correlated with serum creatinine, while the expression of DEFB1 in urine samples of DN is negatively correlated with serum creatinine. In addition, the expression of CX3CR1 in DN urine samples was positively correlated with proteinuria, while the expression of DEFB1 in DN urine samples was negatively correlated with proteinuria. Finally, according to the level of proteinuria, DN patients were divided into nephrotic proteinuria group (n = 24) and subrenal proteinuria group. There were significant differences in urinary AGR2, CCR2 and DEFB1 between the two groups by unpaired t test (P < 0.05). CONCLUSIONS: Our study provides new insights into the role of immune-related biomarkers in DN tubulointerstitial injury and provides potential targets for early diagnosis and treatment of DN patients. Seven different genes ( AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1, FSTL1 ), as promising sensitive biomarkers, may affect the progression of DN by regulating immune inflammatory response. However, further comprehensive studies are needed to fully understand their exact molecular mechanisms and functional pathways in DN.
RESUMEN
Background: Autophagy is an essential cellular process involving the self-degradation and recycling of organelles, proteins, and cellular debris. Recent research has shown that autophagy plays a significant role in the occurrence and development of kidney diseases. However, there is a lack of bibliometric analysis regarding the relationship between autophagy and kidney diseases. Methods: A bibliometric analysis was conducted by searching for literature related to autophagy and kidney diseases in the Web of Science Core Collection (WoSCC) database from 2000 to 2022. Data processing was carried out using R package "Bibliometrix", VOSviewers, and CiteSpace. Results: A total of 4,579 articles related to autophagy and kidney diseases were collected from various countries. China and the United States were the main countries contributing to the publications. The number of publications in this field showed a year-on-year increasing trend, with open-access journals playing a major role in driving the literature output. Nanjing Medical University in China, Osaka University in Japan, and the University of Pittsburgh in the United States were the main research institutions. The journal "International journal of molecular sciences" had the highest number of publications, while "Autophagy" was the most influential journal in the field. These articles were authored by 18,583 individuals, with Dong, Zheng; Koya, Daisuke; and Kume, Shinji being the most prolific authors, and Dong, Zheng being the most frequently co-cited author. Research on autophagy mainly focused on diabetic kidney diseases, acute kidney injury, and chronic kidney disease. "Autophagy", "apoptosis", and "oxidative stress" were the primary research hotspots. Topics such as "diabetic kidney diseases", "sepsis", "ferroptosis", "nrf2", "hypertension" and "pi3k" may represent potential future development trends. Research on autophagy has gradually focused on metabolic-related kidney diseases such as diabetic nephropathy and hypertension. Additionally, PI3K, NRF2, and ferroptosis have been recent research directions in the field of autophagy mechanisms. Conclusion: This is the first comprehensive bibliometric study summarizing the relationship between autophagy and kidney diseases. The findings aid in identifying recent research frontiers and hot topics, providing valuable references for scholars investigating the role of autophagy in kidney diseases.
RESUMEN
BACKGROUND: Recently, several systematic reviews (SRs) and meta-analyses (MAs) of Tripterygium wilfordii polyglycoside (TWP) have reported significant benefits on diabetic kidney disease (DKD). However, the adoption of TWP for DKD remains uncommon. This study aimed to evaluate and summarize the current evidence on TWP for DKD. METHODS: We searched PubMed, Web of Science, SINOMED, Embase, Cochrane Library, CNKI database, Wan Fang database, and VIP database, up to June 4, 2022. SRs of TWP on DKD were included. Two authors independently assessed eligibility, extracted data, and graded the quality of evidence. We appraised the reporting and methodological quality of the included studies based on the PRISMA statement and AMSTAR 2. RESULTS: We included 19 SRs and MAs. Seventeen MAs of proteinuria were identified; all suggested TWP exhibited anti-proteinuria function on DKD. Of these, only 2 were graded as moderate quality of evidence. Eighteen MAs estimated the reno-protective effect of TWP; nine of them showed that TWP improved renal function, including 2 MAs rated as moderate quality of evidence. Eleven SRs showed the serum albumin level was elevated in the TWP group. Of those, four were rated as moderate quality of evidence. Fourteen MAs of the incidence of adverse events were included. Twelve MAs indicated TWP increased the risk of adverse events, of which 4 were graded with moderate quality of evidence. Twenty of the 27 items in the PRISMA checklist were adequately reported with more than 75% compliance among the included SRs, while five of the 12 items in the PRISMA checklist for abstract were found to have less than 50% compliance. The overall reporting quality of SRs published in English was higher than that in Chinese. The methodological quality of the included SRs appraised by AMSTAR-2 ranged from critically low to moderate. CONCLUSION: TWP appears effective for DKD on improving proteinuria and increasing the level of serum albumin, accompanied by a higher risk of adverse events. The evidence would be more credible and valuable to guide decision if the quality of the SRs and primary studies is improved. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021249560.
