Ri-Bao Wei

Luteolin is a natural flavonoid exhibiting multiple pharmacological activities. Renal anaemia is an important complication of chronic kidney disease (CKD). Whether luteolin can ameliorate renal interstitial fibrosis-induced renal anaemia remains unclear. We examined the therapeutic effects of luteolin in in vitro and in vivo models of renal interstitial fibrosis-induced renal anaemia. After high-throughput sequencing analysis of animal samples, we screened differentially expressed genes (DEGs) associated with luteolin-mediated improvements, performed GO and KEGG functional and pathway enrichment analyses, and validated the mechanism in vitro and in vivo. In vivo, haemoglobin and haematocrit were increased significantly, blood urea nitrogen and creatinine were decreased significantly, and the degree of renal interstitial injury and fibrosis was significantly alleviated in luteolin-treated mice compared with model mice. Erythropoietin (EPO) and hypoxia inducible factor 2A (HIF2A) levels were significantly increased and alpha smooth muscle actin (α-SMA), collagen I (COLI) and fibronectin (FN) levels were significantly decreased. Transcriptomic analysis revealed significant increases in sirtuin 1 (SIRT1) and forkhead box O3 (FOXO3) after luteolin intervention; these effects were validated in vitro and in vivo. Combined treatment with luteolin and the SIRT1 activator resveratrol or the SIRT1 inhibitor sirtinol and SIRT1–siRNA transfection revealed that blocking SIRT1 reduced FOXO3 expression and significantly decreased the benefits of luteolin, while resveratrol had the opposite effects. Molecular docking analysis indicated a stable conformation between luteolin and SIRT1. In vitro and in vivo systematic and transcriptomic studies showed that luteolin attenuates renal anaemia caused by renal fibrosis through the SIRT1/FOXO3 pathway.

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Immune imbalance has become an important factor in the progression of chronic kidney disease (CKD). Molecular typing of CKD may be key to achieving precise treatment. xCell allows immune cell phenotyping in CKD. We integrated two independent microarray datasets and divided 87 CKD patients into two subgroups using unsupervised consensus clustering to study the correlation between CKD and patient sex, age, and CKD stage. We found different expression patterns and clinical characteristics between the two groups. CKD stage was more advanced in cluster I than in cluster II, and the weighted gene coexpression network analysis module characteristics showed enrichment of interferon and leukocyte-associated immune pathways in cluster I. Differentially expressed gene analysis revealed the 12 most significantly changed genes, of which sirtuin 1 (SIRT1) was significantly downregulated in cluster I. Gene set enrichment analysis identified multiple immune-related processes involved in CKD. xCell immune infiltration analysis revealed the significant upregulation of natural killer T (NKT) cells and the significant downregulation of most T and B cell types in cluster I. SIRT1 showed a significant negative correlation with NKT cell infiltration but a positive correlation with CD4⁺ T cell and natural killer cell infiltration. We systematically studied the molecular typing of the CKD transcriptome and estimated the degree of immune cell infiltration based on molecular subtypes. Our results indicate that different subgroups may have unique gene expression patterns and immune dysregulation patterns, thus providing a basis for precise treatment and immune research in CKD.

In this study, we focused on the influencing factors of renal anaemia in patients with IgA nephropathy and constructed a nomogram model. We divided 462 patients with IgA nephropathy diagnosed by renal biopsy into anaemic and non-anaemic groups. Then, the influencing factors of renal anaemia in patients with IgA nephropathy were analysed by least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression, and a nomogram model for predicting renal anaemia was established. Eventually, nine variables were obtained, which are easy to apply clinically. The areas under the receiver operating characteristic (ROC) curve and precision-recall (PR) curve reached 0.835 and 0.676, respectively, and the C-index reached 0.848. The calibration plot showed that the model had good discrimination, accuracy, and diagnostic efficacy. In addition, the C-index of the model following internal validation reached 0.823. Decision curve analysis suggested that the model had a certain degree of clinical significance. This new nomogram model of renal anaemia combines the basic information, laboratory findings, and renal biopsy results of patients with IgA nephropathy, providing important guidance for predicting and clinically intervening in renal anaemia.

Objective: This study aims to investigate the influences of renal anemia on the pathogenesis of IgA nephropathy using propensity score matching (PSM). Methods: Renal biopsies from 462 patients with IgA nephropathy were enrolled in this study. PSM was used to balance intergroup covariates, and matching results were verified using a dot-plot of standardized mean differences and histograms of the propensity score distribution and distance distribution. The matched data were used to analyze the impact of renal anemia on the pathological indicators of IgA nephropathy by logistic regression. Results: A total of 132 pairs of patients from the renal anemia group and the non-renal anemia group were matched by PSM; after matching, the standard deviations of 13 covariates were within 0.25. Multivariate logistic regression results suggested that the CKD4-5 stage of IgA nephropathy and tubular atrophy/interstitial fibrosis >50% were independent risk factors for renal anemia. Conclusions: Via PSM, we demonstrated that stitial fibrosis are correlated with renal anemia in IgA nephropathy. In clinical practice, renal anemia in patients with IgA nephropathy of CKD3 stage or above should be closely monitored and managed.

Objective: Few studies with large sample populations concerning renal anaemia and IgA nephropathy have been reported worldwide. The purpose of this cross-sectional study was to examine the clinical and pathological characteristics and influencing factors associated with renal anaemia in patients with IgA nephropathy, which is the most common aetiology of chronic kidney disease. Methods: A total of 462 hospitalised patients with IgA nephropathy confirmed by renal biopsy who met the inclusion criteria were consecutively recruited from January 2014 to January 2016. Their general information, routine blood test results, blood chemistries, estimated glomerular filtration rates (eGFRs) and renal pathologies were collected. The Oxford classification was used to characterise the renal pathologies. Univariable and multivariate logistic regression models were used to analyse the influencing factors of anaemia associated with IgA nephropathy. Results: The incidence of renal anaemia was 28.5% (132/462 patients) in our study (21.3% in males and 38.9% in females). The anaemia type was primarily normocytic and normochromic. The rate of anaemia in patients with eGFR values of 30–59 mL/min/1.73 m ² was higher than that in patients with an eGFR >60 mL/min/1.73 m ² (42.9% vs 17.8%, p<0.001). Notably, in the group with eGFR values 50% (OR 2.57, 95% CI 1.22 to 5.40). Conclusions: The female sex, hypoalbuminaemia, reduced eGFR levels and severe renal tubulointerstitial lesions were correlated with renal anaemia in patients with IgA nephropathy. These results provide new insight into our understanding of anaemia in IgA nephropathy and may improve the management and treatment of clinical renal anaemia.

BACKGROUND:Studies on insulin resistance (IR) in chronic kidney disease (CKD) patients are rare, and its exact mechanism remains unclear. In this study, we explored the molecular mechanism of IR with chronic renal failure (CRF) and interventions to a...

BACKGROUND:Albuminuria has been associated with cardiovascular events, but whether such an association can be explained by endothelial dysfunction is not fully understood. In this study, we examined the relationship between the urine albumin-to-creat...

To investigate the protective effects and potential mechanisms of Shenhua Tablet (肾华片, SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI).