Iranian journal of kidney diseases最新文献

{"title":"The Outcome of Pauci-immune Crescentic Glomerulonephritis and Its Prognostic Factors; A single Center Case Series.","authors":"Neda Najafi, Sharzad Ossareh, Mitra Mehrazma, Mohsen Vahedi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Pauci-immune crescentic glomerulonephritis (GN) is the most common cause of rapidly progressive GN in adults. The aim of this study was to determine the outcome of patients with pauci-immune crescentic GN and risk factors of the development of end-stage kidney disease (ESKD) in these patients.</p><p><strong>Methods: </strong>This case series study was carried on 120 patients with pauci-immune crescentic GN biopsied in our center betwen 1998 and 2016. Inclusion criteria were age > 16 years, at least one crescentic glomerulus, maximally 1+ deposition of immunoglobulins and complement components at fluorescent microscopy, and at least 6 months follow-up. The main outcomes were ESKD and death.</p><p><strong>Results: </strong>The study population included 120 patients with pauciimmune crescentic GN (mean age was 47 ± 17 years and 49.1% male). There was no significant difference in outcome between patients with diffuse or focal crescentic GN. Seventy-two patients (60%) developed ESKD and 31 patients (25.8%) died. The need for dialysis at admission, lower baseline hemoglobin and GFR and GFR at four months and high percentage of glomerulosclerosis and interstitial fibrosis had a significant relationship with low kidney survival (P < .05). The rate of ESKD was higher in patients who did not receive cyclophosphamide therapy, due to focal crescentic GN or high chronicity, compared to patients who received it (70.7 vs. 28.5%, P < .001).</p><p><strong>Conclusion: </strong>In our study, a high percentage of patients with pauciimmune crescentic GN developed ESKD. Low first GFR and high chronicity in biopsy were associated with lower kidney survival. Failure to administer cyclophosphamide in seemingly limited or advanced cases, together with late referral may have led to poor prognosis.  DOI: 10.52547/ijkd.7545.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Efficacy and Long-term Prognosis of High Flux Hemodialysis Combined with Different Frequency Hemodiafiltration in the Treatment of Middle-Aged and Elderly Patients with Uremia.","authors":"Xiaoyan Jiang, Fengjun Sun, Haiyan Huang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>To analyze the clinical efficacy and long-term prognosis of high flux hemodialysis (HFHD) combined with different frequency hemodiafiltration (HDF) in uremic patients.</p><p><strong>Methods: </strong>86 middle-aged and elderly patients with uremia were divided into the HF group (HFHD combined with high-frequency HDF) and the LF group (HFHD combined with low-frequency HDF). The changes between the two groups in various indicators after 12 months of dialysis and the survival rate at 5 years of follow-up were compared. We used SPSS 25.0 software for data analysis.</p><p><strong>Results: </strong>The differences of the levels of serum albumin, hemoglobin and transferrin in HF Group was significantly higher than LF Group before and after treatment (P < .05). The differences of the levels and clearance rate of calcium, phosphorus, parathyroid hormone, β2-microglobulin and cysteine protease inhibitor C in the patients' blood after dialysis were significantly higher in HF Group than in LF Group (P < .05). The all-cause mortality rate, new cardiovascular event rate, new cerebrovascular event rate, and new infection event rate of HF Group were significantly lower than those of LFHD group, respectively (P < .05). The LF Group had a significantly higher risk of all-cause mortality events, new cardiovascular cerebrovascular and infectious events than the HF Group (P < .05).</p><p><strong>Conclusion: </strong>1 week/time HDF combined with HFHD can more effectively eliminate the vascular related toxins in middle-aged and elderly patients with uremia, improve their nutritional status, treatment effect, and long-term prognosis.  DOI: 10.52547/ijkd.7864.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Pyroptosis of Renal Tubular Epithelial Cells by Puerarin via Regulation of lncRNA NEAT1 Ameliorating Chronic Renal Failure.","authors":"Jing Yang, Baochao Li, Jiangming Wang, Wenxing Fan","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney disease (CKD) is one of the major chronic human diseases worldwide. Puerarin, extensively used in traditional Chinese medicine, has shown favorable clinical effects in treating CKD. Here, we aimed to elucidate the mechanism by which puerarin alleviates CKD.</p><p><strong>Methods: </strong>We constructed an animal model of CKD and intragastrically administered 400 mg/kg puerarin to the rat models. The extent of kidney injury was evaluated by performing hematoxylin and eosin staining. Then, we quantified the renal function indicators, inflammatory cytokines, apoptosis-related factors, and pyroptosis-related factors. HK-2 cells were treated with lipopolysaccharide (400 ng/mL) in H2O2 (200 μM) to induce oxidative stress. Then, the cells were treated with puerarin and transfected with overexpressed lncRNA NEAT1 vectors. Finally, the regulatory functions of lncRNA NEAT1 in cell apoptosis and pyroptosis were investigated.</p><p><strong>Results: </strong>Puerarin treatment alleviated kidney damage and suppressed inflammation and apoptosis in the CKD rat model. Puerarin ameliorated pyroptosis in the CKD model by inhibiting caspase-1 and GSDMD-N expression. LncRNA NEAT1 was down-regulated in the CKD model after puerarin treatment. Puerarin enhanced cell viability when lncRNA NEAT1 was overexpressed, and the inhibition of apoptosis was reversed in the LPS/H2O2-stimulated HK-2 cells. Furthermore, lncRNA NEAT1 overexpression blocked the anti-pyroptosis effect of Puerarin in the CKD model.</p><p><strong>Conclusion: </strong>Puerarin inhibits pyroptosis and inflammation by regulating lncRNA NEAT1, thereby ameliorating CKD.  DOI: 10.52547/ijkd.7565.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promotion of Inflammation, Apoptosis, and Inhibition of Autophagy by Overexpression of lncRNA SNHG12 in Acute Kidney Injury.","authors":"Jiaqing Zhang, Liang Li, Yanhui Yu, Yan Fang, Jian Li, Jinji Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Introduction. There is a dispute regarding the roles of newly discovered lncRNAs in acute kidney injury (AKI). Therefore, this study discussed long non-coding RNA (lncRNA) small nuclear host gene 12 (SNHG12) in AKI and its molecular mechanism.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS) induction was treated into renal tubular epithelial cells (HK-2 cells) to induce septic AKI in vitro. In the cell model, SNHG12, miR-1270, and tubulin beta class I (TUBB) expression patterns, along with p-p65, cleaved caspase-3, Beclin-1, p62, and autophagy related 7 (ATG7) protein expressions, were determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. Cell viability was evaluated by cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) cytotoxicity assay, while apoptosis and inflammation were assessed by flow cytometry and enzymelinked immunosorbent assay (ELISA), respectively. At last, the mechanistic interaction between SNHG12, miR-1270, and TUBB was identified.</p><p><strong>Results: </strong>SNHG12 was highly expressed in LPS-induced HK-2 cells. Functionally, knocking down SNHG12 increased cell viability and autophagy, while inhibited LDH release, inflammation, and apoptosis. Mechanically, SNHG12 absorbed miR-1270 to upregulate TUBB expression, thereby aggravating inflammation, apoptosis, and inhibiting autophagy in AKI.</p><p><strong>Conclusion: </strong>SNHG12 promotes inflammation, apoptosis, and autophagy by targeting the miR-1270/TUBB axis in AKI.  DOI: 10.52547/ijkd.7903.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetic Kidney Disease Without Albuminuria: A New Entity in Diabetic Nephropathy.","authors":"Nooshin Ahmadi, Atefeh Amouzegar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Non-albuminuric diabetic kidney disease (NA-DKD) is characterized by progressive loss of kidney function with an annual loss of estimated glomerular filtration rate (eGFR) more than 3 mL/ min/ 1.73m2 per year. NA-DKD is also associated with the late manifestation of diabetic kidney disease, characterized by reduced eGFR (< 60 mL/min/ 1.73m2), in the absence of albuminuria (urine albumin-to-creatinine ratio [UACR] less than 30 mg/g. The typical glomerular changes seen in diabetic nephropathy are less frequently observed in normoalbuminuric patients, while they predominantly show mesangial expansion and tubulointerstitial and vascular changes. The prevalence of NA-DKD has been increasing during the past decade, with a wide range of prevalence in different studies. It seems that patients with NA-DKD are more likely to be female and have better metabolic profile including a lower Hb A1c, lower triglyceride, lower cholesterol, lower BMI and systolic blood pressure, and lower rate of retinopathy. Compared to patients with albuminuria, those with NA-DKD show a lower risk for progression to end-stage kidney disease (ESKD), or rapid decline in eGFR. They also have increased risks of death and hospitalization for heart failure compared with non-DKD diabetic patients, but a lower risk in comparison with albuminuric DKD, regardless of GFR. There is no effective treatment for this phenotype of the disease, but limited data support the use of SGLT2 inhibitors to slow chronic kidney disease progression along with appropriate metabolic risk factor control. More clinical research and pathologic studies are needed for a better understanding of the phenotype, prevention, and treatment methods of the disease.  DOI: 10.52547/ijkd.7966.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139671794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role and Mechanism of NUP160-regulated Autophagy in Pathogenesis of Diabetic Nephropathy.","authors":"Jiayong Xie, Ying Yuan, Gang Yao, Wenjuan Yu, Qiang Zhu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Introduction. Diabetes mellitus (DM) is one of the most common chronic diseases worldwide, and diabetic nephropathy (DN) is the most significant complication of DM, which is highly prevalent and difficult to cure. This research project aims to investigate the role and mechanism of Nucleoporin 160kDa (NUP160)-regulated autophagy in the pathogenesis of DN.</p><p><strong>Methods: </strong>NUP160 levels in diabetic and non-diabetic kidney tissues were measured by Western blot, and the connection between NUP160 and renal function of DN patients was analyzed. The podocytes were divided into four groups, namely the standard group (culture medium: standard glucose solution), high glucose (HG) group (HG solution), HG+si-NUP160 group (HG solution+si-NUP160 transfection) and HG+si-NC group (HG solution+si-NUP 160 transfection) for the determination of apoptosis by flow cytometry and measurements of LC3B, Prostacyclin-62 (P62), Janus kinase 2 (JAK2) and Signal transducer and activator of transcription3 (STAT3) by Western blot.</p><p><strong>Results: </strong>In DN patients, NUP160 decreased in podocytes and was inversely proportional to Blood urea nitrogen (BUN), Serum creatinine (Scr) and β2-Microglobulin (β2-MG) (P < .05). Compared with a standard group, the apoptosis rate, P62 level, and the ratios of phosphorylation-JAK2 (p-JAK2)/JAK2, phosphorylation-STAT3 (p-STAT3)/STAT3, and LC3B-Ⅱ/LC3B-Ⅰ elevated in the other three groups (P < .05). Apoptosis rate and P62 level, p-JAK2/JAK2 and p-STAT3/STAT3 ratios increased, and LC3B-Ⅱ/LC3B-Ⅰ ratio decreased in the HG+si-NUP160 group (P < .05), while those in HG+si-NC group showed no evident changes, compared with HG group (P > .05).</p><p><strong>Conclusion: </strong>NUP160 is downregulated in DN and can affect cellular autophagy through the activation of JAK2/STAT3 signaling pathway.  DOI: 10.52547/ijkd.7884.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Farnesoid Receptors and Nrf2-mediated Genes in Gentamicin-induced Nephrotoxicity in Rat: A Time-course Study.","authors":"Mohammad Reza Ashrafi, Azadeh Khalili, Seyed Ali Hashemi, Roham Mazloom, Saeed Changizi-Ashtiyani, Gholamreza Bayat","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Farnesoid-X-activated receptor (FXR) is considered as an upstream controller which could influence the other key regulatory genes encoding cellular antioxidant defense system.</p><p><strong>Methods: </strong>Thirty-five male Wistar rats (240 ± 20 g) were randomly allocated into five groups: 1) control, 2) received gentamicin (100 mg/kg/d) for three days (GM-3d), 3) seven days (GM-7d), 4) 10 days (GM-10d), and 5) 14 consecutive days (GM-14d). Biochemical measurements of BUN and serum creatinine (SCr), histological assessment of renal samples as well as molecular analysis using real-time qRT-PCR were used to investigate the pattern of changes in different levels.</p><p><strong>Results: </strong>Administration of gentamicin was associated with a significant increase in the BUN and SCr until the 10th day, which then suddenly dropped at the day 14. Meantime, the maximum histological distortion was also seen on the 10th day but in a similar pattern, 14th day was associated with clear improvement. Compared to the control value, the maximum reduction in the mRNA expression of Farnesoid X-activated receptor (FXR), nuclear factor erythroid 2-related factor 2 (Nrf2) and Glutathione cysteine ligase-modulatory subunit (GCLM), occurred at the 3rd and 7th days, respectively. Compared to the control, the mRNA expression of the mentioned genes significantly increased up to day 14. Apart from the 3rd day, the mRNA expression of alpha-glutathione S-transferase (α-GST) and superoxide dismutase (SOD) showed a similar descending and ascending pattern at 7th and 10th days, respectively.</p><p><strong>Conclusion: </strong>The expression of FXR, as an upstream controller gene and its downstream pathways mediated by Nrf2, could play a role in gentamicin-induced nephrotoxicity but the pattern of expression was rather biphasic at the acute phase or the subacute ones.  DOI: 10.52547/ijkd.7523.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simple Memorable Formulas for Screening Hypertension in Children: Based on the New American Academy of Pediatrics Guideline.","authors":"Afagh Hassanzadeh Rad, Jahangir Kamalpour, Behrad Badeli, Daniel Badeli, Hamidreza Badeli","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>Hypertension (HTN), also known as high blood pressure (BP), is a major global risk factor for cardiovascular and kidney diseases. Although annual BP screenings for children over three years of age are recommended, underdiagnosis of HTN in children is common. To address this issue, the American Academy of Pediatrics updated its guideline for screening and managing high BP in children in 2017, which can be cumbersome to implement in clinical practice due to the numerous cut-off points and tables. The purpose of our study is to design formulas to detect HTN in children based on the new Clinical Practice Guideline for screening and management of high BP in children and adolescents.</p><p><strong>Methods: </strong>In this research, we analyzed forty-eight cut-off points using the 90th percentile systolic and diastolic BPs for the fifth percentile height. The final mathematical model consisted of four formulas based on different ages and sex which in turn were rounded by 0.1 and 1.0 for both systolic and diastolic BPs. The formulas were further modified to be lower than the 95th percentile systolic BPs for the fifth percentile of height to minimize false negative results.</p><p><strong>Results: </strong>As evidenced by the tables included in this paper, except for a few exceptions, all rounded systolic and diastolic values for both sexes were equal to or lower than the 90th percentile. In a few cases where the cutoff points calculated by the formula were higher than the ones provided in the 2017 guideline, the differences were less than 2 mmHg.</p><p><strong>Conclusion: </strong>In this study to address the complexity of the routine guidelines, we present simplified formulas for screening children aged 1 to 12 years in figures and tables and recommend their use, particularly in office and emergency settings, as an easier-to-implement first step in screening for HTN in children.  DOI: 10.52547/ijkd.7525.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormalities of the Serum proteomic in thrombosis after CVC catheterization in patients with end-stage renal disease.","authors":"Li Wang, Xi Mei, Yangang Zhou, Jun Zeng, Ting Yang, Lumiu Liao, Man Xiong, Xiaoshan Zhao, Rui He","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>This study utilized serum proteomics with tandem mass tags (TMT) to investigate potential biomarkers associated with femoral central venous catheter (CVC) thrombosis in endstage kidney disease (ESKD) patients. TMT proteomics analysis on serum samples was conducted to identify proteins with distinct expression levels that may be linked to thrombosis. The findings have important implications for enhancing anticoagulant procedures, catheter closure techniques, and determining optimal intervention timing for post-catheterization dialysis.</p><p><strong>Methods: </strong>Thirty ESKD patients with CVC receiving hemodialysis between May 2021 and October 2022 at the First Affiliated Hospital of Chengdu Medical College were included in the study, and grouped according to vascular color Doppler ultrasound results, including 23 patients in the thrombo-positive group and 7 patients in the thrombo-negative group. Selection criteria were: 1) Patients with ESKD candidate for hemodialysis initiation; 2) no dialysis access has been placed previously, and CVC needs to be inserted as a temporary access; 3) patients volunteered to participate in this clinical study. Clinical data, blood tests, coagulation function, and biochemical parameters were collected and analyzed on the 14th day after catheterization. Color ultrasonography was conducted on the same day to categorize patients into two groups: those with thrombus-positive results and those with thrombus-negative results.</p><p><strong>Results: </strong>TMT proteomics analysis identified twenty-eight differently expressed proteins, including 16 upregulated and 12 downregulated proteins. Enrichment analysis demonstrated nine proteins that were significantly enriched in four pathways within the thrombus-positive group after CVC insertion. Enzyme-linked immunosorbent assay (ELISA) test confirmed the TMT proteomics findings, specifically highlighting significant differences in human plasma kallikrein B1 (KLKB1) and angiopoietin-like protein 3 (ANGPTL3) levels on the 14th day after CVC insertion. Additionally, KLKB1, fibrinogen (FIB), D-dimer, and fibrinogen degradation products (FDP) levels were significantly elevated, while ANGPTL3 levels were decreased on the 14th day after CVC insertion in the thrombus-positive ESKD patient group.</p><p><strong>Conclusion: </strong>Monitoring coagulation status post-CVC catheterization and evaluating potential biomarkers like KLKB1 and ANGPTL3 can contribute to the development of personalized treatment plans, improving the quality of hemodialysis and the overall quality of life for ESKD patients.  DOI: 10.52547/ijkd.7671.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of PHACTR4 as A New Biomarker for Diabetic Nephropathy and Its Correlation with Glomerular Endothelial Dysfunction and Immune Infiltration.","authors":"Baixue Yu, Mei Meng, Tingting Li, Yi Shi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>The pathophysiology of diabetic nephropathy (DN) is fundamentally dependent on glomerular endothelial cells (GECs), which are a crucial portion of the glomerular filtration barrier. This study aimed to identify biomarker candidates associated with GECs dysfunction in DN by combining microarray and single-cell sequencing dataset analysis.</p><p><strong>Methods: </strong>Microarray dataset GSE30528 was downloaded from the Gene expression omnibus (GEO) database. Key gene sets for diabetic kidney disease (DKD) were selected by using weighted gene co-expression network analysis (WGCNA). Biomarker candidates were then identified using least absolute shrinkage and selection operator (LASSO) logistic regression. The single-cell sequencing data (GSE131882) was used to explore the biological functional differences in glomerular endothelium between the control and DKD groups. The diagnostic efficiency of the selected biomarker was tested in the Receiver operating characteristic (ROC) curve. Moreover, we used the single-sample gene set enrichment analysis (ssGSEA) to compare immune cell infiltration between DKD and control groups. RT-PCR was used to validate the selected gene expression in cultured glomerular endothelial cells under high glucose stimulation.</p><p><strong>Results: </strong>Phosphatase and actin regulator 4 (PHACTR4) was ultimately selected as the key GEC-related biomarker in DKD. Significantly downregulated PHACTR4 mRNA expression was further validated in human glomerular endothelial cells (HGECs) under high glucose stimulation by using RT-PCR. The decreased PHACTR4 was found to be associated with abnormal endothelial proliferation and neo-angiogenesis. Additionally, immune infiltration analysis revealed that PHACTR4 was negatively associated with inflammatory infiltration, especially pro-inflammatory cells including activated CD4 and CD8 T cells, B cells, and Mast cells, indicating PHACTR4 downregulation may exacerbate inflammatory reaction.</p><p><strong>Conclusion: </strong>PHACTR4 is a potential diagnostic marker for DKD and plays an essential role in aberrant glomerular endothelial proliferation and inflammation in DKD.  DOI: 10.52547/ijkd.7858.</p>","PeriodicalId":14610,"journal":{"name":"Iranian journal of kidney diseases","volume":null,"pages":null},"PeriodicalIF":1.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138477732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}