The ANGPTL4-HIF-1α loop: a critical regulator of renal interstitial fibrosis.

BACKGROUND: Renal interstitial fibrosis (RIF) is a progressive, irreversible terminal kidney disease with a poor prognosis and high mortality. Angiopoietin-like 4 (ANGPTL4) is known to be associated with fibrosis in various organs, but its impact on the RIF process remains unclear. This study aimed to elucidate the role and underlying mechanisms of ANGPTL4 in the progression of RIF. METHODS: In vivo, a chronic kidney disease (CKD) rat model of renal interstitial fibrosis was established via intragastric administration of adenine at different time points (4 and 6 weeks). Blood and urine samples were collected to assess renal function and 24-h urinary protein levels. Kidney tissues were subjected to HE and Masson staining for pathological observation. Immunohistochemistry and real-time quantitative PCR (qRT‒PCR) were performed to evaluate the expression of ANGPTL4 and hypoxia-inducible factor-1α (HIF-1α), followed by Pearson correlation analysis. Subsequently, kidney biopsy tissues from 11 CKD patients (6 with RIF and 5 without RIF) were subjected to immunohistochemical staining to validate the expression of ANGPTL4. In vitro, a fibrosis model of human renal tubular epithelial cells (HK2) was established through hypoxic stimulation. Subsequently, an HIF-1α inhibitor (2-MeOE2) was used, and ANGPTL4 was manipulated using siRNA or plasmid overexpression. Changes in ANGPTL4 and fibrosis markers were analyzed through Western blotting, qRT‒PCR, and immunofluorescence. RESULTS: ANGPTL4 was significantly upregulated in the CKD rat model and was significantly positively correlated with renal injury markers, the fibrotic area, and HIF-1α. These results were confirmed by clinical samples, which showed a significant increase in the expression level of ANGPTL4 in CKD patients with RIF, which was positively correlated with HIF-1α. Further in vitro studies indicated that the expression of ANGPTL4 is regulated by HIF-1α, which in turn is subject to negative feedback regulation by ANGPTL4. Moreover, modulation of ANGPTL4 expression influences the progression of fibrosis in HK2 cells. CONCLUSION: Our findings indicate that ANGPTL4 is a key regulatory factor in renal fibrosis, forming a loop with HIF-1α, potentially serving as a novel therapeutic target for RIF.

[18F]sodium fluoride positron emission tomography: a systematic bibliometric review from 2008 to 2022.

Background: As a noninvasive diagnostic tool, fluorine-18-labelled sodium fluoride positron emission tomography ([18F]NaF PET) has been increasingly applied in clinical practice due to its excellent imaging performance, attracting more attention from clinical practitioners. However, with the continuous development of technology and growth of knowledge, the field of [18F]NaF PET is changing. Nevertheless, few studies have conducted quantitative analyses of the literature in this field. Therefore, in this study, we used bibliometric methods to analyze the trends, content distribution, and frontiers of this field from multiple perspectives, including social and international structure, conceptual structure, and intellectual structure. Methods: This study used the Web of Science (WOS) core database as the data source and retrieved literature related to [18F]NaF PET between 2008 and 2022. CiteSpace and VOSviewer software were then employed for bibliometric analysis. This study performed co-occurrence analysis and citation analysis to investigate the characteristics of [18F]NaF PET in 3 aspects. Results: A total of 682 articles related to [18F]NaF PET were collected during the period from 2008 to 2022. The author, Alavi, had the highest number of publications (67 articles). In terms of institutions, the University of Edinburgh had the highest number of publications (64 articles). The United States (300 articles) was the country with the highest number of published articles. Keyword co-occurrence analysis revealed that [18F]NaF PET-related technologies, bone metastasis (prostate cancer and breast cancer), and atherosclerosis were prominent research directions in this field. In terms of highly cited authors, Even-Sapir had the highest citation count (188 citations). Regarding highly cited journals, the Journal of Nuclear Medicine ranked as the most highly cited journal. The literature co-citation clustering and timeline graph showed that atherosclerotic plaques, bone metastasis, and the clinical applications of [18F]NaF PET were topics of active research in this field. Conclusions: There has been an increase in the literature published in the field of [18F]NaF PET from 2008 to 2022. The United States holds a prominent position in the field of [18F]NaF PET. Arteriosclerosis and bone metastasis are the main topics in this field and at the forefront of research.

The relationship between coronary artery calcification and bone metabolic markers in maintenance hemodialysis patients.

BACKGROUND: To study the influencing factors for coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients and the relationship between CAC and bone metabolism markers and to attempt to find a reliable marker linking vascular calcification and bone metabolism in MHD patients. METHODS: A total of 123 patients were enrolled. CAC was assessed by multislice spiral computed tomography (MSCT), and the CAC score (CACS) was evaluated using the Agaston method. Routine laboratory parameters, including triglycerides (TG), total cholesterol (TC), glucose (Glu), calcium (Ca), phosphorus (P), magnesium (Mg), etc., were measured. Serum markers of bone metabolism, such as alkaline phosphatase(ALP), calcitonin (CT), 25-hydroxy vitamin D [25-(OH)D], intact parathyroid hormone (iPTH), total type I procollagen amino-terminal peptide (tPINP), N-terminal mid-fragment of osteocalcin (N-MID OC), and ß-type I collagen crosslinked carboxyl-terminal peptide (ß-CTX), were also measured. RESULTS: Among 123 MHD patients, 37 patients (30.08%) did not have CAC, and 86 patients (69.92%) had CAC, including 41 patients (47.67%) with mild calcification and 45 patients (52.33%) with moderate to severe calcification. Age, Body Mass Index(BMI), the prevalence of hypertension and diabetes mellitus, TC, Glu, P, and Ca×P in the calcification group were higher than those in the noncalcification group, whereas Mg, iPTH, tPINP, N-MID OC, and ß-CTX were lower than those in the noncalcified group (P < 0.05). Compared with the mild calcification group (0 0.05). A logistic regression model was used to evaluate the influencing factors for CAC. The results showed that age, BMI, TC, Glu, P, and Ca×P were risk factors for CAC and its severity in MHD patients, whereas diabetes mellitus, Mg, and N-MID OC were protective factors for CAC in MHD patients. In addition, N-MID OC was a protective factor for the severity of CAC. After adjusting for the corresponding confounding factors, the results of the risk factors were consistent, and N-MID OC was still an independent protective factor for CAC and its severity. CONCLUSIONS: Elevated serum P and Ca×P were independent risk factors for CAC in MHD patients, and serum Mg may be an independent protective factor for CAC. CAC was closely related to abnormal bone metabolism and bone metabolic markers in MHD patients. Relatively low bone turnover can promote the occurrence and development of CAC. N-MID OC may be a reliable bone metabolic marker linking vascular calcification and bone metabolism in MHD patients.

[Establishment of a prognostic nomogram model for predicting acute renal injury in patients with moderate and severe burns].

OBJECTIVE: To establish a prediction model of acute kidney injury (AKI) in moderate and severe burn patients, so as to provide basic research evidence for early identification of burn-related AKI. METHODS: Patients who were admitted to the department of plastic burn surgery of the Affiliated Hospital of Southwest Medical University from November 2018 to January 2021 were selected, and their clinical characteristics, laboratory examinations and other indicators were recorded. Multivariate Logistic regression analysis was used to screen out the risk factors of AKI related to moderate and severe burns, and R software was used to establish the nomogram of moderate and severe burn patients complicated with AKI. The Bootstrap method model was used for internal verification by repeating sample for 1 000 times. Consistency index and calibration curve were used to evaluate the accuracy of the model, and the receiver operator characteristic curve (ROC curve) and the area under the curve (AUC) were used to evaluate the prediction efficiency, decision curve analysis (DCA) was used to evaluate the clinical utility of the model. RESULTS: A total of 186 patients with moderate and severe burn were included, among which 54 patients suffered from AKI, and the incidence rate was 29.03%. Multivariate Logistic regression analysis showed that the total burn surface area [TBSA; odds ratio (OR) = 1.072, 95% confidence interval (95%CI) was 1.031-1.115, P = 0.001], estimated glomerular filtration rate (eGFR; OR = 0.960, 95%CI was 0.931-0.990, P = 0.010), neutrophil (NEU; OR = 1.190, 95%CI was 1.021-1.386, P = 0.026), neutrophil/lymphocyte ratio (NLR; OR = 0.867, 95%CI was 0.770-0.977, P = 0.019), D-dimer (OR = 4.603, 95%CI was 1.792-11.822, P = 0.002) were the risk factors for patients with moderate and severe burn complicated with AKI. Taking the above indexes as predictive factors, a nomogram prediction model was established, the ROC curve was plotted with AUC of 0.998 (95%CI was 0.988-1.000). Optimum threshold of ROC curve was -0.862, the sensitivity was 98.0% and the specificity was 98.2%, and the consistency index was 0.998 (95%CI was 0.988-1.000). The calibration curve showed that the prognostic nomogram model was accurate, DCA showed that most patients can benefit from this model. CONCLUSIONS: The burned patients with higher TBSA, NEU, NLR, D-dimer and lower eGFR tend to suffer from AKI. The nomogram based on the above five risk factors has high accuracy and clinical value, which can be used as a predictive tool to evaluate the risk of AKI in moderate and severe burn patients.

The role of urinary Dickkopf-3 in the prediction of acute kidney injury: a systematic review meta-analysis.

BACKGROUND: To systematically evaluate the diagnostic efficacy of urinary Dickkopf-Related Protein 3 (DKK-3) in acute kidney injury and to explore the clinical application value of urinary DKK-3. METHOD: English databases (PubMed, Embase, Cochrane, and WOS) and Chinese databases (VIP, WanFang data, and China National Knowledge Internet) were screened for relevant papers published before March 12, 2023. After literature screening and data extraction, quality assessment was performed according to the QUADAS-2 scoring system. Then, the combined diagnostic and predictive parameters were calculated using a bivariate mixed effect meta-analysis model. Deek's funnel plot asymmetry test assessed publication bias, and Fagan's nomogram plot was used to verify its clinical utility. RESULT: A total of 5 studies involving 2787 patients were included in this meta-analysis, of which 4 focused on contrast-induced acute kidney injury (CI-AKI) and 1 focused on AKI associated with cardiac surgery. The analysis showed that urine Dickkopf-3 has high diagnostic accuracy for AKI, with a sensitivity of 0.55 (95% CI [0.41, 0.68]), specificity of 0.80 (95% CI [0.70, 0.87]), positive likelihood ratio (PLR) of 2.7 [1.8, 4.1], negative likelihood ratio (NLR) of 0.56 [0.42, 0.75], diagnostic odds ratio (DOR) of 5 [3, 9], and AUC of 0.74 [0.70-0.77]. We did not perform subgroup analyses for predictive value due to the small number of included studies. CONCLUSION: Urinary DKK3 may have limited predictive ability for acute kidney injury, especially for AKI associated with cardiac surgery. Therefore, urinary DKK3 may serve as a potential predictor for AKI. However, clinical studies with larger samples are still needed for validation.

Noninvasive Assessment of Renal Fibrosis of Chronic Kidney Disease in Rats by [68Ga]Ga-FAPI-04 Small Animal PET/CT and Biomarkers.

Renal fibrosis is the most common pathological feature and common pathway of progression in chronic kidney disease (CKD). We evaluated [68Ga]Ga-FAPI-04 small animal positron emission tomography/computed tomography (PET/CT) and biomarkers as noninvasive assessments of renal fibrosis (RF) in CKD rats to generate new ideas for clinical diagnosis. A rat model of renal fibrosis was administered adenine by gavage (n = 28), and the control group was given 0.9% NaCl by gavage (n = 20). At different time points (weeks 1, 2, 4, and 6), five rats were randomly selected from the two groups for [68Ga]Ga-FAPI-04 small animal PET/CT imaging. At the same time, the expression of Fibroblast activation protein (FAP) in renal tissue and the expression levels of type III procollagen N-terminal peptide (PIIINP), transforming growth factor (TGF-ß1), Klotho, and sex-determining region Y-box protein 9 (SOX9) in blood and urine were determined. FAP was highly expressed in the renal tissue of rats in the CKD group and expression increased with the progression of renal fibrosis. [68Ga]Ga-FAPI-04 small animal PET/CT examination showed that the uptake of radioactive tracers in the CKD group was higher than that in the control group, and SUVmax (r = 0.9405) and target-to-background ratio (TBR) (r = 0.9392) were positively correlated with renal fibrosis. The serum levels of PIIINP, TGF-ß1, and SOX9 in CKD rats were significantly higher than those in the control group and were positively correlated with RF (r = 0.8234, r = 0.7733, and r = 0.7135, respectively) and SUVmax (r = 0.8412, r = 0.7763, and r = 0.6814, respectively). Compared with the control group, the level of serum Klotho decreased and was negatively correlated with RF (r = -0.6925) and SUVmax (r = -0.6322). Compared with the control group, the levels of PIIINP and TGF-ß1 in urine were positively correlated with RF (r = 0.8127 and r = 0.8077, respectively) and SUVmax (r = 0.8400 and r = 0.8177, respectively). Urine Klotho decreased compared with the control group and was negatively correlated with RF (r = -0.5919) and SUVmax (r = -0.5995). The change in urine SOX9 was not statistically significant. In conclusion, compared with renal biopsy, [68Ga]Ga-FAPI-04 small animal PET/CT shows renal fibrosis quickly and noninvasively. PIIINP, TGF-ß1, and Klotho in serum and urine may be used as biomarkers of RF, and serum SOX9 is expected to become a new diagnostic biomarker of RF.

Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis.

Currently, there is no consensus on whether maintenance dialysis increases cancer risk in patients with end-stage renal disease (ESRD). Therefore, this study was to systematically evaluate the risk of cancer among ESRD patients undergoing maintenance dialysis. Related studies on the impact of maintenance dialysis on cancer risk were retrieved from PubMed, Embase, Cochrane Library, and other databases from their respective inceptions to 19 February 2021. ESRD patients receiving maintenance dialysis were classified into cancer including non-melanoma skin cancer (NMSC) and cancer excluding NMSC. Standardized incidence ratio (SIR) with its 95% confidence interval (95% CI) was calculated to assess cancer risk. Fourteen studies were included in the meta-analysis. The risk of cancer in patients undergoing maintenance dialysis (with or without NMSC) was significantly higher than controls both in cancer including NMSC (SIR = 1.38, 95% CI: 1.27-1.49, P < 0.001) and cancer excluding NMSC (SIR = 1.34, 95% CI: 1.23-1.47, P < 0.001). Subgroup results identified the higher risk of cancer incidence in both men and women receiving maintenance dialysis. Meanwhile, elevated excess risks were observed among patients with younger age and shorter follow-up time (P < 0.001). Meanwhile, the combined SIR of bladder, cervix, colorectum, kidney, liver, thyroid, tongue, and other cancers were all increased (P < 0.05). ESRD patients undergoing dialysis has higher risk of cancer.

Probiotics, Prebiotics, and Synbiotics for Patients on Dialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The current systematic review and meta-analysis investigated the effects of probiotic, prebiotic, and synbiotic administration on inflammation, metabolic parameters, nutritional status, and uremic toxin in dialysis patients. METHODS: Up to June 2021, publications were searched in Cochrane Library, PubMed, EMBASE, and Web of Science databases. The protocol was submitted to the International Prospective Register of Systematic Reviews and was approved. RESULTS: This meta-analysis included 18 randomized controlled trials which were eligible. This meta-analysis discovered that probiotic, prebiotic, and synbiotic supplements could reduce C-reactive protein (standardized mean difference (SMD), -0.38; 95% confidence interval (CI), -0.68 to -0.08; P = .01), interleukin 6 (SMD, -0.48; 95% CI, -0.76 to -0.20; P = .00), and indoxyl sulfate (SMD, -0.24; 95% CI, -0.48 to -0.01; P = .045) and increase high-density lipoprotein cholesterol (SMD, 0.25; 95% CI, 0.03 to 0.46; P = .025) compared with the control group but had no significant influence on tumor necrosis factor α, albumin, hemoglobin, triglyceride, total cholesterol, low-density lipoprotein cholesterol, calcium, phosphorus, uric acid, or p-cresyl sulfate in dialysis patients. CONCLUSIONS: Probiotic, prebiotic, and synbiotic administration could reduce C-reactive protein, interleukin 6, and indoxyl sulfate and increase high-density lipoprotein cholesterol in dialysis patients. To better examine the impact, large-scale, long-term, controlled diets and well-designed randomized controlled trials are needed.

An atypical anti-GBM disease complicated by idiopathic nodular glomerulosclerosis: Case report.

Both atypical anti-glomerular basement membrane (anti-GBM) disease and idiopathic nodular glomerulosclerosis are rare diseases. We report a case of a 53-year-old non-diabetic male who presented with leg edema, nephritic range proteinuria, microscopic hematuria, and decreased renal function. The renal biopsy demonstrated membranoproliferative glomerulonephritis (MPGN) pattern of glomerular injury with focal crescent and segmental nodular glomerulosclerosis. The immunofluorescence studies showed intense linear IgG (IgG1 and IgG4) deposits along the GBM but negative serology. Electron microscopy demonstrated GBM thickening and fibrillar deposition. The presence of MPGN with crescents and the linear IgG along the GBM were consistent with a diagnosis of atypical ant-GBM disease. Superimposed nodular glomerulosclerosis was considered to be idiopathic by excluding other glomerular diseases characterized by fibrillar deposition and nodular glomerulosclerosis. Both diseases were found to have a strong causative association with patient's history of long-term heavy smoking. This unusual case with combination of atypical anti-GBM disease and idiopathic nodular glomerulosclerosis, has brought great challenge for the diagnosis and also made the clinical course highly complicated. This nodular glomerulosclerosis with anti-GBM-like glomerulonephritis may represent a distinct pattern of kidney injury observed in heavy smokers.

Clinical value of M1 macrophage-related genes identification in bladder urothelial carcinoma and in vitro validation.

Background: Tumor microenvironment (TME) takes a non-negligible role in the progression and metastasis of bladder urothelial carcinoma (BLCA) and tumor development could be inhibited by macrophage M1 in TME. The role of macrophage M1-related genes in BLCA adjuvant therapy has not been studied well. Methods: CIBERSOR algorithm was applied for identification tumor-infiltrating immune cells (TICs) subtypes of subjects from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. We identified potential modules of M1 macrophages by weighted gene co-expression network analysis (WGCNA). Nomogram was determined by one-way Cox regression and lasso regression analysis for M1 macrophage genes. The data from GEO are taken to verify the models externally. Kaplan-Meier and receiver operating characteristic (ROC) curves validated prognostic value of M1 macrophage genes. Finally, we divided patients into the low-risk group (LRG) and the high-risk group (HRG) based on the median risk score (RS), and the predictive value of RS in patients with BLCA immunotherapy and chemotherapy was investigated. Bladder cancer (T24, 5637, and BIU-87) and bladder uroepithelial cell line (SV-HUC-1) were used for in vitro validation. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to validate the associated genes mRNA level. Results: 111 macrophage M1-related genes were identified using WGCNA. RS model containing three prognostically significant M1 macrophage-associated genes (FBXO6, OAS1, and TMEM229B) was formed by multiple Cox analysis, and a polygenic risk model and a comprehensive prognostic line plot was developed. The calibration curve clarified RS was a good predictor of prognosis. Patients in the LRG were more suitable for programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte associate protein-4 (CTLA4) combination immunotherapy. Finally, chemotherapeutic drug models showed patients in the LRG were more sensitive to gemcitabine and mitomycin. RT-qPCR result elucidated the upregulation of FBXO6, TMEM229B, and downregulation of OAS1 in BLCA cell lines. Conclusion: A predictive model based on M1 macrophage-related genes can help guide us in the treatment of BLCA.

Genistein improves mitochondrial function and inflammatory in rats with diabetic nephropathy via inhibiting MAPK/NF-κB pathway.

PURPOSE: To investigate the effect of genistein on inflammation and mitochondrial function of diabetic nephropathy. METHODS: Diabetic nephropathy model was established in Sprague-Dawley rats. Automatic biochemical analyzer was employed to detect the kidney function index, serum creatinine, serum urea nitrogen, and 24 h-urine protein and blood glucose. Hematoxylin and eosin staining and periodic acid Schiff staining were used to observe renal morphology. Mitochondrial changes and podocyte integrity were monitored by transmission electron microscope. The expression levels of mfn2, NOX4, P53, MAPK, and NF-κB were detected by Western blotting. The changes of mitochondrial membrane potential were measured by JC-1. The level of mfn2 was assessed by immunofluorescence assay. RESULTS: Genistein ameliorated the kidney function with reduced Scr and blood glucose. The expressions of NOX4, MAPK, p65 and p53 were downregulated, while the expression of mnf2 was the opposite in genistein-treated kidneys. Further investigations revealed that genistein reduced expansion of mesangial matrix and oxidative stress, protected podocyte integrity and increased mitochondrial membrane potential. CONCLUSIONS: Genistein could alleviate diabetic nephropathy through inhibiting MAPK/NF-κB pathway, improving mitochondrial function and anti-inflammatory.

Autosomal dominant tubulointerstitial kidney disease with a novel heterozygous missense mutation in the uromodulin gene: A case report.

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a progressive chronic disease that is inherited in an autosomal dominant fashion. Symptoms include hyperuricemia, gout, interstitial nephritis, renal cysts, and progressive renal damage that can lead to end-stage renal disease. Mutations in the uromodulin gene (UMOD) characterize the ADTKD-UMOD clinical subtype of this disease. To date, > 100 UMOD mutations have been identified. Early diagnosis of ADTKD-UMOD is important to treat the disease, slow down disease progression, and facilitate the identification of potentially affected family members. CASE SUMMARY: We report a 40-year-old man harboring a novel heterozygous missense mutation in UMOD (c.554G>T; p. Arg185Leu). The patient had hyperuricemia, gout, and chronic kidney disease. The same mutation was detected in his daughter, aunt and cousin. CONCLUSION: A single nucleotide substitution in exon 3 of UMOD was responsible for the heterozygous missense mutation (c.554G>T, p.Arg185Leu).

Obstructive jaundice in a patient with polycystic liver disease complicated with polycystic kidney and polycystic lung: A case report.

RATIONALE: Polycystic liver disease (PLD) is an autosomal-dominant disorder that is commonly associated with autosomal-dominant polycystic kidney disease (PKD) but rarely complicated with polycystic lung. Here, we report the first case of severe obstructive jaundice caused by multiple liver cysts in a patient with PLD complicated by PKD and polycystic lung. PATIENT CONCERNS: A 72-year-old man with a history of PLD complicated with polycystic kidney presented with progressive jaundice, hematuria, poor appetite, nausea, and weight loss since 3 months. DIAGNOSIS: PLD complicated with PKD and polycystic lung was identified using computed tomography, and obstructive jaundice was identified using magnetic resonance imaging and magnetic resonance cholangiopancreatography. INTERVENTIONS: The patient could not undergo surgery, and was therefore treated with combined bilirubin adsorption and continuous veno-venous hemofiltration. OUTCOMES: The patient's symptoms and laboratory findings improved after bilirubin adsorption and continuous veno-venous hemofiltration. Unfortunately, the patient was unable to continue the treatment due to financial reasons, and died of shock most likely due to cyst rupture. LESSONS: Imaging examination of the lungs is necessary for patients with PLD. Although infrequent, jaundice can occur in these patients and cause severe hyperbilirubinemia. When surgery is contraindicated, blood purification may serve as an alternative treatment for patients with PLD-related obstructive jaundice.

Renal pathology in patients with occupational exposure to carbon disulphide: A case series.

AIM: Carbon disulphide (CS2 ) is widely used as an organic solvent. However, there is little information available regarding the clinical manifestations and the pathological features of kidney injury caused by CS2 . The current study aimed to describe the renal manifestations of a group of patients with long-term occupational exposure to CS2 . METHODS: Ten patients with long-term exposure to CS2 and visiting a single centre were enrolled, with their clinical features recorded. Renal biopsies were taken from all patients, and their pathological findings were documented. RESULTS: All patients came from the same chemical fibre factory. Their mean age at enrollment was 36.9 ± 2.4 years, and each patient had a CS2 exposure duration exceeding 10 years. Eight patients (80%) presented with proteinuria and none had hematuria. Two patients (20%) had underlying hypertension and five (50%) had increased serum creatinine levels. Light microscopic examination of their renal biopsy specimens revealed diffuse mesangial cell proliferation and mesangial hyperplasia in all patients. Moreover, three patients (30%) had nodular hyperplasia, resembling the lesions of diabetic nephropathy. Variable degrees of tubular atrophy and interstitial infiltrations of lymphocytes and monocytes were observed in all patients. Similarly, lectron microscopic examination showed glomerular mesangial cell proliferation and mesangial hyperplasia. Immunopathological staining for IgA and IgG, complements or hepatitis B markers (hepatitis B surface antigen and e antigen-antibody) are negative in all patients. CONCLUSION: Long-term occupational exposure to CS2 may be associated with renal injury, although the renal pathological features are often non-specific.

[Expression of BMP2/Smad1/Runx2 Signal Pathway in Renal Artery of Rat with Vascular Calcification].

OBJECTIVE: To investigate the activation and its role of bone morphogenetic protein 2 (BMP2)/Smad1/Runt-related transcription factor 2 (Runx2) signal pathway in renal artery of rat models with vascular calcification. METHODS: Twenty four male SD rats were randomly divided into control group and calcification group. Rat vascular calcification model was constructed by administration of vitamin D3 plus nicotine. Vascular calcification was confirmed by Von Kossa staining and calcium content was detected by calcium assay. Real time-PCR was applied to detect the expression of BMP2, Smad1, Runx2 mRNA, and immunohistochemistry was used to measure the protein levels of BMP2, Smad1, Runx2, α-smooth muscle actin (α-SMA). RESULTS: Von Kossa staining showed a large number of black granules deposited in renal artery. Calcium content in calcification group was significantly higher than that in normal group. Compared with the control group, the expressions of BMP2, Smad1 and Runx2 mRNA in renal artery were increased in calcification group. The protein levels of BMP2, Smad1 and Runx2 were higher while the expression of α-SMA was lower in calcification group than those in control group. The correlation analysis was found a positivie correlation between the calcium content and BMP2 mRNA (r = 0.655, P < 0.05), Smad1 mRNA (r = 0.735, P < 0.05), Runx2 mRNA (r = 0.734, P < 0.05). CONCLUSION: The expression of BMP2/Smad1/Runx2 signal pathway was strongly correlated with the severity of vascular calcification, which may be involved in the occurrence and development of vascular calcification.

[Relation between bone matrix proteins and monocyte chemoattractant protein-1 in renal small artery in diabetic nephropathy rats].

OBJECTIVE: To observe the expressions of bone matrix proteins and monocyte chemoattractant protein-1 ((MCP-1) in the renal arteriole of diabetic nephropathy (DN) rats and analyze their correlations and roles in diabetic nephropathy. METHODS: Adult Sprague-Dawley male rats were used to establish the animal model of diabetic nephropathy induced by peritoneal injection of 55 mg/kg of streptozocin. Calcium deposit around the renal arteriole was observed by alizarin red staining. The protein and mRNA levels of core-bind factor alpha 1 (cbfalpha1), bone morphogenetic protein 2 (BMP-2) and matrix Gla protein (MGP) in renal arteriole of DN rats were detected by immunohistochemistry, in-situ hybridization and real-time PCR. The biochemical indices were detected by routine test. RESULTS: 1. Blood glucose and Urine protein of 24 h were significantly increased in the renal arteriole of DN rats versus the control rats (P < 0.05), serum creatinine (SCr) and phosphorus were significantly increased from 12 weeks. 2. Little deposit of calcium salt was observed in the renal arteriole of DN rats at the 4th week and a large amount of deposit was observed at 24th week, but no calcium deposit was observed in control rats. 3. Cbfalpha1 and BMP-2 expressions were significantly increased in the renal arteriole of DN rats from 4 to 24 weeks vs. the control rats. MGP mRNA expression in the renal arteriole of DN rats was significantly decreased from 4 to 24 weeks. MCP-1 expression was obviously upregulated in the renal arteriole of DN rats at 24th week versus that at 4th and 12th week. No MCP-1 expression was observed in the renal arterioles of control rats. MCP-1 were positively correlated with the expression of cbfalpha1 and BMP-2. CONCLUSION: Bone matrix proteins has already expressed in renal arteriole before the formation of vascular calcification. MCP-1 can affect the expression of cbfalpha1, BMP-2; cbfalpha1, BMP-2, MGP and MCP-1 may be involved in the formation of vascular lesions of DN.

[Effects of atorvastatin on expression of peroxisome proliferation activated receptor gamma in unilateral ureteral obstruction in rats].

OBJECTIVE: To observe the expression of peroxisome proliferation activated receptor gamma (PPAR gamma) at different periods in renal interstitium and to study the effect of atorvastatin on the protein expression of PPAR gamma in unilateral ureteral obstruction (UUO) in a rat model. METHODS: Forty-five female Sprague-Dawley (SD) rats were divided into three groups: the sham operation group, the model group and the atorvastatin group. The latter two groups underwent UUO and then received vehicle only or atorvastatin (10 mg.kg(-1).d(-1)) by daily gastric gavage, from three days before the UUO operation to the day of sacrifice . The sham operation rats received vehicle. Five rats of each group were sacrificed respectively at 5, 10 and 15 days after surgery. Histological changes in renal tissue were observed by hematoxylin and eosin (HE) and Masson stain. Immunohistochemistry for PPAR gamma was performed in renal interstitium at each time point. RESULTS: Interstitial expansion and fibrosis in ureter obstructed kidney was prominent in the model group. Atorvastatin seemed to have ameliorated interstitial expansion and fibrosis in atorvastatin group. Detectable basic PPAR gamma expression was observed in renal inner medulla of rats in sham operation group, and it was mainly concentrated in collecting tubules. In UUO rats, PPAR gamma expression was found increased and extended to renal tubular epithelial cells. Increased PPAR gamma expression was found on the 5th day after UUO, and significant PPAR gamma expression was found on the 10 th day after UUO. The increased PPAR gamma expression was found to be downregulated on the 15 th day after UUO, but still significantly increased compared with that of the model group at the same time point (all P<0.01). Atorvastatin could significantly increase the expression of PPAR gamma as compared with the model group at each time point (all P<0.01). CONCLUSION: PPAR gamma expression was found increased, and it appeared in renal tubular epithelial cells in UUO rats, Atorvastatin may play a protective role in the kidney by activating PPAR gamma, thus alleviating renal interstitial fibrosis following UUO in rats.