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.

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.

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.

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.

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.

Quantitative vessel density analysis of macular and peripapillary areas by optical coherence tomography angiography in adults with primary nephrotic syndrome.

PURPOSE: To compare the microvascular parameters of macular and peripapillary areas in adults with primary nephrotic syndrome (PNS) and healthy controls (HCs). METHODS: In this cross-sectional study, optical coherence tomography angiography (OCTA) was used to evaluate the changes in retinal microvascular in 37 adult patients with PNS and 30 HCs in this study. All subjects underwent OCTA for measuring vascular density (VD), perfusion density (PD), and foveal avascular zone (FAZ) in the superficial capillary plexus (SCP) and optical coherence tomography (OCT) for measuring central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness. The following clinical data of the PNS group were collected: hemoglobin, platelet, total protein, albumin, prealbumin, creatinine, urea nitrogen, glomerular filtration rate, blood lipid, urinary protein, urine microalbumin, urine microalbumin/creatinine, 24-h urine volume, and 24-h urine protein quantification. The OCTA data were compared between patients with PNS and HCs, and the correlation between the OCTA data and clinical data was analyzed in the PNS group. RESULTS: VD and PD in the macular area of the PNS group were significantly lower than those in the HC group (VD: 17.025 ± 2.229 vs. 18.290 ± 0.721, P = 0.001; PD: 0.417 ± 0.058 vs. 0.450 ± 0.019, P = 0.003). No significant differences in the FAZ area and perioptic disc microvascular parameters were observed between the two groups, and patients in the PNS group showed consistent changes in the left and right eyes. VD and PD in the central macular area were positively correlated with plasma prealbumin level (VD: ρ = 0.541, P = 0.001; PD: ρ = 0.562, P < 0.001) and negatively correlated with urinary protein level (VD: ρ = -0.579, P < 0.001; PD: ρ = -0.596, P < 0.001). CONCLUSIONS: In adult patients with PNS, the decrease in VD and PD was mainly occurred in the macular area. Partly vascular density of the macular area was positively correlated with plasma prealbumin level and negatively correlated with urinary protein level. OCTA provides a convenient, non-invasive and effective method for evaluating and monitoring retinal microcirculation damage in patients with PNS.

Value of [68Ga]Ga-FAPI-04 imaging in the diagnosis of renal fibrosis.

PURPOSE: Renal fibrosis is a pathological state in the progression of chronic kidney disease. Early detection and treatment are vital to prolonging patient survival. Renal puncture examination is the gold standard for renal fibrosis, but it has several limitations. This study aims to evaluate the diagnostic performance of a novel PET radiotracer, [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04, which specifically images fibroblast activation protein (FAP) expression for renal fibrosis. METHODS: All patients underwent renal puncture before receiving [68Ga]Ga-FAPI-04 PET/CT imaging. They then underwent [68Ga]Ga-FAPI-04 PET/CT and immunochemistry examinations. The data obtained were analyzed. RESULTS: The [68Ga]Ga-FAPI-04 PET/CT examination results demonstrated that almost all patients (12/13) exhibited increased radiotracer uptake. The maximum standardized uptake value (SUVmax) in patients with mild, moderate, and severe fibrosis was 3.92 ± 1.50, 5.98 ± 1.6, and 7.67 ± 2.23, respectively. CONCLUSION: Compared with renal puncture examination, non-invasive imaging of FAP expression through [68Ga]Ga-FAPI-04 PET/CT quickly demonstrates bilateral kidney conditions with high sensitivity. [68Ga]Ga-FAPI-04 PET/CT can facilitate the evaluation of disease progression, diagnosis, and the development of a treatment plan.

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.

The 100 top-cited articles on chronic kidney disease-mineral and bone disorder: A bibliometric analysis.

BACKGROUND: Tremendous scientific research has been conducted on chronic kidney disease-mineral and bone disorder (CKD-MBD), while only a few bibliometric analyses have been conducted in this field. In this study, we aim to identify 100 top-cited articles on CKD-MBD and analyze their main characteristics quantitatively. METHODS: Web of Science was used to search the 100 top-cited articles on CKD-MBD. The following data were extracted and analyzed from the selected articles: author, country of origin, institutions, article type, publication journal, publication year, citation frequency, and keywords. RESULTS: Among the 100 top-cited articles, the number of citations ranged between 181 to 2157, with an average number of citations of approximately 476. These articles were published in 23 different journals, with Kidney International publishing the most articles (n = 32). The largest contributor was the United States (n = 63), which was also the country that conducted the most collaborative studies with other nations. The University of Washington contributed the largest number of articles (n = 37). Block GA was the most common first-author (n = 7). The majority of articles were clinical research articles (n = 73), followed by reviews (n = 15). Although almost half of the articles had no keywords, the most concerned research direction was CKD-associated bone disease. CONCLUSION: This is the first bibliometric study of the 100 top-cited articles on CKD-MBD. This study provides the main academic interests and research trends associated with CKD-MBD research.

Composite dietary antioxidant index is associated with renal anemia: a cross-sectional study.

An increasing evidence suggested that chronic kidney disease (CKD) is closely related to oxidative stress, and dietary antioxidant intake can serve as a primary preventive measure for CKD. However, the relationship between composite dietary antioxidant index (CDAI) and renal anemia is not well understood. We postulated that elevated CDAI levels would be inversely related to a higher likelihood of renal anemia. The standardized calculation of CDAI was performed to investigate the relationship between them by a binary regression model. A non-linear relationship was examined through restricted cubic spline curves, and then pinpointed the inflection point. Subgroup analysis was then used to assess the robustness of the model. Finally 5880 participants were included in the study and a notable correlation between CDAI and renal anemia was found (P < 0.0001). In the multivariate linear regression model with adjustment for all confounding variables, the odds ratio (OR) and 95% confidence interval (CI) was 0.96 (0.94, 0.98; P < 0.0001), A non-linear relationship between CDAI and renal anemia was explored through restricted cubic splines, with a inflection at 6.005. Before the inflection point, for each unit rise in CDAI, the prevalence of renal anemia decreased by 5.7%. Subgroup analysis showed no statistically significant differences in interactions between any subgroups (P > 0.05). Our findings indicated a non-linear negative correlation between CDAI and renal anemia. The causal relationship still needs to be further clarified through large-scale prospective studies.

Evaluation of retinal microcirculation by optical coherence tomography angiography in patients with primary membranous nephropathy.

BACKGROUND: Primary membranous nephropathy (PMN) patients may experience retinal microvascular changes. However, current diagnostic methods for PMN are not accurate in analyzing these modifications. In the present study, optical coherence tomography angiography (OCTA) was used for quantitative measurement of microvascular changes in the eyes of PMN patients. METHODS: A total of 26 patients with PMN and 26 healthy control (HC) were evaluated in this cross-sectional study. Optical coherence tomography (OCT) and OCTA were used to collect retinal thickness (RT) and microvascular parameters in the macula and optic disk in the superficial capillary plexus (SCP) of all subjects. Clinical data were collected from the PMN group. The OCT and OCTA data for PMN and HC group were compared, and the correlation between the OCTA and clinical data in the PMN group was determined. RESULTS: Vascular density (VD) and perfusion density (PD) in the macular area of the PMN group were significantly lower than those of the HC group, especially in the temporal quadrant. No significant difference in the foveal avascular zone (FAZ), optic disc microvascular parameters, RT, and retinal nerve fiber layer (RNFL) thickness was observed between the two groups. Correlation was noted between VD and PD in the macular area and clinical indicators, such as serum creatinine, serum urea nitrogen, 24 h urine volume and urinary protein concentration. CONCLUSION: Microvascular alterations in PMN patients occurred before ocular symptoms. The present quantitative study proposed a measurement method for detecting early retinal vascular injury in PMN patients.

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.

[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.

Efficacy and safety of plasma diafiltration: Review of case reports and case series.

Plasma diafiltration (PDF), a blood purification procedure that combines dialysis with plasma filtration by a selective membrane, has been used to treat acute liver failure, sepsis, and other acute conditions. We reviewed 14 eligible case reports and case series that examined PDF in 357 patients to assess its efficacy and safety. Fourteen diseases may be indications for PDF. The primary indication in the included studies was acute liver failure without obvious inducement or cause not mentioned. Eighty-three patients reached the primary endpoint (31 deaths, 52 recoveries) and the efficacy was 62.7%. There were large changes in 16 toxins or clinical markers after PDF, including total bilirubin, IL-18, IL-6. In conclusion, PDF appears to be an effective treatment for clearance of bilirubin and other inflammatory mediators in patients with acute liver injury or a disease characterized by a systemic inflammatory state. Randomized controlled trials are needed to compare PDF with other blood purification methods, such as plasma exchange and the Molecular Adsorbent Recirculating System™.

Altered serum metabolome associated with vascular calcification developed from CKD and the critical pathways.

Introduction: Vascular calcification (VC) is more likely to be detected in the chronic kidney disease (CKD) population. The mechanism of VC development from CKD is different from that for simple VC and has always been a major research area. The aim of this study was to detect alterations in the metabolome during development of VC in CKD and to identify the critical metabolic pathways and metabolites involved in its pathogenesis. Methods: Rats in the model group were given an adenine gavage combined with a high-phosphorus diet to imitate VC in CKD. The aorta calcium content was measured and used to divide the model group into a VC group and non-vascular calcification group (non-VC group). The control group was fed a normal rat diet and given a saline gavage. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to determine the altered serum metabolome in the control, VC, and non-VC groups. The identified metabolites were mapped into the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (https://www.genome.jp/kegg/) for pathway and network analyses. Result: There were 14 metabolites that changed significantly in the VC group, with three metabolic pathways playing critical roles in the pathogenesis of VC in CKD: steroid hormone biosynthesis; valine, leucine and isoleucine biosynthesis; and pantothenate and CoA biosynthesis. Conclusion: Our results indicated changes in the expression of steroid sulfatase and estrogen sulfotransferase, and down-regulation of the in situ synthesis of estrogens in the VC group. In conclusion, the serum metabolome alters significantly during the pathogenesis of VC in CKD. The key pathways, metabolites, and enzymes we identified are worth further study and may become a promising therapeutic target for the treatment of VC in CKD.

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.

[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.