cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13241136
title: Clinical features, risk factors, and clinical burden of acute kidney injury in older adults

description: <b><i>Background:</i></b> Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study investigated the clinical features, risk factors, and clinical burden in this population. <b><i>Methods:</i></b> A retrospective observational study was performed with the clinical data of inpatients at Guangdong Geriatrics Institute from 1 August 2012, to 31 December 2016. AKI was classified into community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), and the risk factors for AKI were ranked by weight. The relationships between AKI and adverse outcomes during hospitalization were analyzed using univariate and multivariate logistic regression. <b><i>Results:</i></b> In total, 6126 patients were enrolled, and 1704 patients developed AKI (27.8%): 6.3% had CA-AKI, and 21.5% had HA-AKI. In total, 1425 (23.3%), 202 (3.3%), and 77 (1.3%) patients had stage 1, 2 and 3 AKI, respectively. Age, dementia, moderate/severe renal disease, moderate/severe liver disease, metastatic solid tumor, female sex, congestive heart failure, chronic pulmonary disease, diabetes mellitus with chronic complications, non-metastatic tumor and lymphoma were independent risk factors for HA-AKI. The first five were also independent risk factors for CA-AKI. After multiple adjustment, AKI was associated with intensive care admission (CA-AKI: OR 5.688, 95% CI 3.122–10.361; HA-AKI: OR 4.704, 95% CI 3.023–7.298) and in-hospital mortality (CA-AKI: OR 5.073, 95% CI 2.447–10.517; HA-AKI: OR 13.198, 95% CI 8.133–21.419). <b><i>Conclusion:</i></b> AKI occurs in &gt;25% of older adults in the geriatric ward. In addition to traditional risk factors, dementia and tumors were risk factors for AKI in older adults. AKI is closely related to a poor prognosis.
DOI: 10.6084/m9.figshare.13241136.v1
title: Clinical features, risk factors, and clinical burden of acute kidney injury in older adults

description: <b><i>Background:</i></b> Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study investigated the clinical features, risk factors, and clinical burden in this population. <b><i>Methods:</i></b> A retrospective observational study was performed with the clinical data of inpatients at Guangdong Geriatrics Institute from 1 August 2012, to 31 December 2016. AKI was classified into community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), and the risk factors for AKI were ranked by weight. The relationships between AKI and adverse outcomes during hospitalization were analyzed using univariate and multivariate logistic regression. <b><i>Results:</i></b> In total, 6126 patients were enrolled, and 1704 patients developed AKI (27.8%): 6.3% had CA-AKI, and 21.5% had HA-AKI. In total, 1425 (23.3%), 202 (3.3%), and 77 (1.3%) patients had stage 1, 2 and 3 AKI, respectively. Age, dementia, moderate/severe renal disease, moderate/severe liver disease, metastatic solid tumor, female sex, congestive heart failure, chronic pulmonary disease, diabetes mellitus with chronic complications, non-metastatic tumor and lymphoma were independent risk factors for HA-AKI. The first five were also independent risk factors for CA-AKI. After multiple adjustment, AKI was associated with intensive care admission (CA-AKI: OR 5.688, 95% CI 3.122–10.361; HA-AKI: OR 4.704, 95% CI 3.023–7.298) and in-hospital mortality (CA-AKI: OR 5.073, 95% CI 2.447–10.517; HA-AKI: OR 13.198, 95% CI 8.133–21.419). <b><i>Conclusion:</i></b> AKI occurs in &gt;25% of older adults in the geriatric ward. In addition to traditional risk factors, dementia and tumors were risk factors for AKI in older adults. AKI is closely related to a poor prognosis.
DOI: 10.6084/m9.figshare.11493936
title: Timing of initiation of renal replacement therapy in acute kidney injury: an updated meta-analysis of randomized controlled trials

description: The results from randomized controlled trials (RCTs) concerning the timing of initiation of renal replacement therapy (RRT) for patients with acute kidney injury (AKI) are still inconsistent. We searched for RCTs, as well as relevant references, focusing on the timing of RRT for AKI patients in the Medline, Embase, Cochrane Library, Google Scholar and Chinese databases from their inception to December 2018. We included 18 RCTs from 1997 to 2018 involving 2856 patients. Pooled analyses of all RCTs showed no significant difference in mortality between early initiation and delayed initiation of RRT (RR 0.98, 95% CI: 0.89 to 1.08, <i>p</i> = .7) (<i>I</i><sup>2</sup> = 2%), and similar results were found in critically ill and community-acquired AKI patients, as well as in a subgroup of patients with sepsis and in cardiac surgery recipients. There was also no difference in the incidence of dialysis independence (RR 0.75, 95% CI: 0.47 to 1.2, <i>p</i> = .2) (<i>I</i><sup>2</sup> = 0). However, an early RRT strategy was associated with a significantly higher incidence of the need for RRT for AKI patients (RR 1.24, 95% CI: 1.13 to 1.36, <i>p</i> &lt; .01) (<i>I</i><sup>2</sup> = 34%). As no life-threatening complications occurred, there was no evidence to show any benefit of an early RRT strategy for critically ill or community-acquired AKI patients; in contrast, a delayed strategy might avert the need for RRT.
DOI: 10.6084/m9.figshare.11493936.v1
title: Timing of initiation of renal replacement therapy in acute kidney injury: an updated meta-analysis of randomized controlled trials

description: The results from randomized controlled trials (RCTs) concerning the timing of initiation of renal replacement therapy (RRT) for patients with acute kidney injury (AKI) are still inconsistent. We searched for RCTs, as well as relevant references, focusing on the timing of RRT for AKI patients in the Medline, Embase, Cochrane Library, Google Scholar and Chinese databases from their inception to December 2018. We included 18 RCTs from 1997 to 2018 involving 2856 patients. Pooled analyses of all RCTs showed no significant difference in mortality between early initiation and delayed initiation of RRT (RR 0.98, 95% CI: 0.89 to 1.08, <i>p</i> = .7) (<i>I</i><sup>2</sup> = 2%), and similar results were found in critically ill and community-acquired AKI patients, as well as in a subgroup of patients with sepsis and in cardiac surgery recipients. There was also no difference in the incidence of dialysis independence (RR 0.75, 95% CI: 0.47 to 1.2, <i>p</i> = .2) (<i>I</i><sup>2</sup> = 0). However, an early RRT strategy was associated with a significantly higher incidence of the need for RRT for AKI patients (RR 1.24, 95% CI: 1.13 to 1.36, <i>p</i> &lt; .01) (<i>I</i><sup>2</sup> = 34%). As no life-threatening complications occurred, there was no evidence to show any benefit of an early RRT strategy for critically ill or community-acquired AKI patients; in contrast, a delayed strategy might avert the need for RRT.
DOI: 10.6084/m9.figshare.12851168
title: Glomerular C4 deposition and glomerulosclerosis predict worse renal outcomes in Chinese patients with IgA nephropathy

description: Immunoglobulin A nephropathy (IgAN) is a clinical and pathological syndrome with heterogenous manifestation and progression. Complement activation is involved in the disease. However, the clinical significance of C4 deposition in IgAN is obscure. A multicenter retrospective study was conducted in biopsy-proven IgAN patients. Based on mesangial C4 deposition, patients were divided into two groups. The baseline clinical data and immunopathological phenotypes were compared. The composite endpoint was defined as eGFR decline greater than 50%, doubling of baseline serum creatinine, the occurrence of end-stage renal disease (ESRD). A total of 642 IgAN patients were recruited, with 41 patients showing mesangial C4 deposition. The mesangial C4 positive group showed lower serum albumin, higher proteinuria, and a higher rate of IgG, IgM, and C1q mesangial deposition. After a median follow-up of 43.18 months, 81 (12.62%) patients achieved the composite endpoint. The multivariate Cox regression models identified glomerular C4 deposition (hazard ratios [HR] = 3.22, 95% confidence intervals [CI] = 1.51–6.87, <i>p</i> &lt; 0.01), global sclerosis (G1 vs. G0, HR = 1.90, 95%CI = 1.02–3.52, <i>p</i> = 0.04; G2 vs. G0, HR = 3.72, 95%CI = 1.98–7.00, <i>p</i> &lt; 0.01), male (HR = 1.80, 95%CI = 1.10–2.97, <i>p</i> = 0.02), serum creatinine (HR = 1.01, 95%CI = 1.00–1.01, <i>p</i> &lt; 0.01), triglyceride (HR = 1.17, 95%CI = 1.01–1.35, <i>p</i> = 0.04), proteinuria (HR = 1.07, 95%CI = 1.01–1.13, <i>p</i> = 0.02), serum C3 level (HR = 0.05, 95%CI = 0.01–0.25, <i>p</i> &lt; 0.01), and serum C4 level (HR = 99.59, 95%CI = 8.69–1140.89, <i>p</i> &lt; 0.01) as independent risk factors for poor renal outcomes. Glomerular mesangial C4 deposition and global sclerosis are independent predictors for poor prognosis in IgAN patients.
DOI: 10.6084/m9.figshare.13168189
title: The gut microbiome in differential diagnosis of diabetic kidney disease and membranous nephropathy

description: Diabetic kidney disease (DKD) and membranous nephropathy (MN) are the two major causes of end-stage renal disease (ESRD). Increasing evidence has shown that intestinal dysbiosis is associated with many diseases. The aim of this study was to explore the composition of the gut microbiome in DKD and MN patients. 16S rRNA gene sequencing was performed on 271 fecal samples (DKD = 129 and MN = 142), and taxonomic annotation of microbial composition and function was completed. We observed distinct microbial communities between the two groups, with MN samples exhibiting more severe dysbiosis than DKD samples. Relative increases in genera producing short-chain fatty acids (SCFAs) in DKD and a higher proportion of potential pathogens in MN were the main contributors to the microbiome alterations in the two groups. Five-fold cross-validation was performed on a random forest model, and four operational taxonomic unit (OTU)-based microbial markers were selected to distinguish DKD from MN. The results showed 92.42% accuracy in the training set and 94.52% accuracy in the testing set, indicating high potential for these microbiome-based markers in separating MN from DKD. Overexpression of several amino acid metabolic pathways, carbohydrate metabolism and lipid metabolism was found in DKD, while interconversion of pentose/glucoronate and membrane transport in relation to ABC transporters and the phosphotransferase system were increased in MN. The composition of the gut microbiome appears to differ considerably between patients with DKD and those with MN. Thus, microbiome-based markers could be used as an alternative tool to distinguish DKD and MN.
DOI: 10.6084/m9.figshare.13168189.v1
title: The gut microbiome in differential diagnosis of diabetic kidney disease and membranous nephropathy

description: Diabetic kidney disease (DKD) and membranous nephropathy (MN) are the two major causes of end-stage renal disease (ESRD). Increasing evidence has shown that intestinal dysbiosis is associated with many diseases. The aim of this study was to explore the composition of the gut microbiome in DKD and MN patients. 16S rRNA gene sequencing was performed on 271 fecal samples (DKD = 129 and MN = 142), and taxonomic annotation of microbial composition and function was completed. We observed distinct microbial communities between the two groups, with MN samples exhibiting more severe dysbiosis than DKD samples. Relative increases in genera producing short-chain fatty acids (SCFAs) in DKD and a higher proportion of potential pathogens in MN were the main contributors to the microbiome alterations in the two groups. Five-fold cross-validation was performed on a random forest model, and four operational taxonomic unit (OTU)-based microbial markers were selected to distinguish DKD from MN. The results showed 92.42% accuracy in the training set and 94.52% accuracy in the testing set, indicating high potential for these microbiome-based markers in separating MN from DKD. Overexpression of several amino acid metabolic pathways, carbohydrate metabolism and lipid metabolism was found in DKD, while interconversion of pentose/glucoronate and membrane transport in relation to ABC transporters and the phosphotransferase system were increased in MN. The composition of the gut microbiome appears to differ considerably between patients with DKD and those with MN. Thus, microbiome-based markers could be used as an alternative tool to distinguish DKD and MN.
DOI: 10.6084/m9.figshare.12197586
title: Interleukin-22 attenuates renal tubular cells inflammation and fibrosis induced by TGF-β1 through Notch1 signaling pathway

description: Transforming growth factor-β1 (TGF-β1) is a crucial factor implicated in the development of renal inflammation and tubulointerstitial fibrosis (TIF). The cytokine interleukin 22 (IL-22) was previously reported to involve in the pathogenesis of chronic inflammatory diseases, however recent studies showed that IL-22 could reduced inflammatory responses and tissue damage. In the present study, we aim to investigate the role and mechanisms of IL-22 in renal tubular cells inflammation and fibrosis induced by TGF-β1. HK-2 cells were treated with TGF-β1 in the presence of IL-22 or the Notch pathway inhibitor dibenzazepine (DBZ) for 48 h. Collagen I (Col I), fibronectin (FN), α-smooth muscle actin (α-SMA), vimentin and E-Cadherin were detected by western blot, proinflammatory factors (TNF-α, IL-6) and chemokines (MCP-1, RANTES) were evaluated by ELISA. Jagged1, Notch1, NICD1, and Hes1 were also detected by western blot. We found TGF-β1 increased the levels of Col I, FN, α-SMA and vimentin in HK-2 cells compared with control, and decreased E-Cadherin level, however, IL-22 restored their expressions partly. IL-22 reduced overexpression of proinflammatory factors (TNF-α, IL-6) and chemokines (MCP-1, RANTES) levels induced by TGF-β1, along with down-regulation of Jagged1, Notch, NICD1 and Hes1. Fibrosis and inflammation in renal tubular cells induced by TGF-β1 could be attenuated by IL-22, and the effects were similar to DBZ treatment. Collectively, our study shows that IL-22 exerts a protective role in renal fibrotic and inflammatory responses induced by TGF-β1 <i>in vitro</i>, which may be through inhibiting Jagged1/Notch1 signaling pathway activation.
DOI: 10.6084/m9.figshare.11853456
title: The predictive value of crescents in the disease progression of lupus nephritis based on the 2018 International Society of Nephrology/Renal Pathology Society Revision System: a large cohort study from China

description: This study analyzed the associations of different crescents’ fraction and clinical features in a Chinese lupus nephritis cohort based on the 2018 revision of ISN/RPS classification system. A total of 288 lupus nephritis patients with complete clinicopathological data and well follow-up was enrolled. The fraction of glomeruli with cellular or fibrocellular crescents based on the new system was reevaluated. The association between crescents fractions and the outcomes were further analyzed. The median follow-up period was 76.5 months. Cellular or fibrocellular crescents were present in 146 (50.7%) of the total individuals. The percentage of crescents were significantly associated with severe clinical renal injury indices and other renal pathological parameter. According to the survival receiver operating characteristic (survival ROC) curve, the optimal cutoff level of cellular or fibrocellular crescents for predicting the composite events was 7.39%. By multivariable Cox hazard analysis, the presence of crescents was predictive of survival from the composite events with a hazard ratio [HR] of 2.5 (95% CI 1.190–5.431; <i>p</i> = .02). Furthermore, when we used absent, present in less than 7.39% of glomeruli, and present in greater than or equal to 7.39% of glomeruli as cutoffs in all the patients, a gradation appeared, with adjusted HRs of 2.9 (95% CI 1.326–6.313; <i>p</i> = .008) for crescents in greater than or equal to 7.39% of glomeruli, in reference to no crescents. We proposed that the crescents were not uncommon and had important clinical significance in lupus nephritis. The cutoff point of crescents as prognosticator might be nearly 7.39%.
DOI: 10.6084/m9.figshare.11853456.v1
title: The predictive value of crescents in the disease progression of lupus nephritis based on the 2018 International Society of Nephrology/Renal Pathology Society Revision System: a large cohort study from China

description: This study analyzed the associations of different crescents’ fraction and clinical features in a Chinese lupus nephritis cohort based on the 2018 revision of ISN/RPS classification system. A total of 288 lupus nephritis patients with complete clinicopathological data and well follow-up was enrolled. The fraction of glomeruli with cellular or fibrocellular crescents based on the new system was reevaluated. The association between crescents fractions and the outcomes were further analyzed. The median follow-up period was 76.5 months. Cellular or fibrocellular crescents were present in 146 (50.7%) of the total individuals. The percentage of crescents were significantly associated with severe clinical renal injury indices and other renal pathological parameter. According to the survival receiver operating characteristic (survival ROC) curve, the optimal cutoff level of cellular or fibrocellular crescents for predicting the composite events was 7.39%. By multivariable Cox hazard analysis, the presence of crescents was predictive of survival from the composite events with a hazard ratio [HR] of 2.5 (95% CI 1.190–5.431; <i>p</i> = .02). Furthermore, when we used absent, present in less than 7.39% of glomeruli, and present in greater than or equal to 7.39% of glomeruli as cutoffs in all the patients, a gradation appeared, with adjusted HRs of 2.9 (95% CI 1.326–6.313; <i>p</i> = .008) for crescents in greater than or equal to 7.39% of glomeruli, in reference to no crescents. We proposed that the crescents were not uncommon and had important clinical significance in lupus nephritis. The cutoff point of crescents as prognosticator might be nearly 7.39%.
DOI: 10.6084/m9.figshare.12197586.v1
title: Interleukin-22 attenuates renal tubular cells inflammation and fibrosis induced by TGF-β1 through Notch1 signaling pathway

description: Transforming growth factor-β1 (TGF-β1) is a crucial factor implicated in the development of renal inflammation and tubulointerstitial fibrosis (TIF). The cytokine interleukin 22 (IL-22) was previously reported to involve in the pathogenesis of chronic inflammatory diseases, however recent studies showed that IL-22 could reduced inflammatory responses and tissue damage. In the present study, we aim to investigate the role and mechanisms of IL-22 in renal tubular cells inflammation and fibrosis induced by TGF-β1. HK-2 cells were treated with TGF-β1 in the presence of IL-22 or the Notch pathway inhibitor dibenzazepine (DBZ) for 48 h. Collagen I (Col I), fibronectin (FN), α-smooth muscle actin (α-SMA), vimentin and E-Cadherin were detected by western blot, proinflammatory factors (TNF-α, IL-6) and chemokines (MCP-1, RANTES) were evaluated by ELISA. Jagged1, Notch1, NICD1, and Hes1 were also detected by western blot. We found TGF-β1 increased the levels of Col I, FN, α-SMA and vimentin in HK-2 cells compared with control, and decreased E-Cadherin level, however, IL-22 restored their expressions partly. IL-22 reduced overexpression of proinflammatory factors (TNF-α, IL-6) and chemokines (MCP-1, RANTES) levels induced by TGF-β1, along with down-regulation of Jagged1, Notch, NICD1 and Hes1. Fibrosis and inflammation in renal tubular cells induced by TGF-β1 could be attenuated by IL-22, and the effects were similar to DBZ treatment. Collectively, our study shows that IL-22 exerts a protective role in renal fibrotic and inflammatory responses induced by TGF-β1 <i>in vitro</i>, which may be through inhibiting Jagged1/Notch1 signaling pathway activation.
DOI: 10.6084/m9.figshare.12294482
title: Genome-wide identification of lncRNAs and mRNAs differentially expressed in human vascular smooth muscle cells stimulated by high phosphorus

description: Cardiovascular events are the primary cause of death for chronic kidney disease patients, which occurred <i>via</i> vascular calcification evolving pathogenically. Although a high level of phosphorus contributes to the induction of osteogenic differentiation of vascular smooth muscle cells (VSMCs), the role of lncRNA in this process awaits further study. In this study, we systematically investigated the variation of gene expression in human VSMCs induced by high phosphorus. LncRNAs and mRNAs expression were revealed by microarray analyses of the control group and high-phosphorus (HP) group. LncRNA-mRNA co-expression network was established based on the specific lncRNA-mRNA relationships. Hierarchical clustering was used to identify a common set of regulated genes. In addition, Gene Ontology enrichment, Kyoto Gene-Encyclopedia and genomic analyses were conducted for the mRNAs differentially expressed under high phosphorus. RT-qPCR results confirmed that the expression of RUNX2, BMP2 and osteocalcin in HP group exhibited significant increases than in control group (<i>p</i> &lt; .05). VSMC in HP group also showed higher intracellular calcium content. Volcano plots results show that 379 mRNAs and 728 lncRNAs different expressed in HP group. LncRNA-mRNA co-expression networks analysis revealed that 8 lncRNAs were the most highly connected lncRNAs. Quantitative analysis indicated that two lncRNAs were confirmed to increase significantly in the HP group. The mRNA expression of NT5E and ICAM1 were higher in group HP, while MAP3K7CL was lower than CON group (<i>p</i> &lt; .05). This study provided a working list of lncRNAs that may be relevant to osteogenic differentiation, which presents a new insights into the mechanism of vascular calcification induced by high phosphorus in VSMCs.
DOI: 10.6084/m9.figshare.12294482.v1
title: Genome-wide identification of lncRNAs and mRNAs differentially expressed in human vascular smooth muscle cells stimulated by high phosphorus

description: Cardiovascular events are the primary cause of death for chronic kidney disease patients, which occurred <i>via</i> vascular calcification evolving pathogenically. Although a high level of phosphorus contributes to the induction of osteogenic differentiation of vascular smooth muscle cells (VSMCs), the role of lncRNA in this process awaits further study. In this study, we systematically investigated the variation of gene expression in human VSMCs induced by high phosphorus. LncRNAs and mRNAs expression were revealed by microarray analyses of the control group and high-phosphorus (HP) group. LncRNA-mRNA co-expression network was established based on the specific lncRNA-mRNA relationships. Hierarchical clustering was used to identify a common set of regulated genes. In addition, Gene Ontology enrichment, Kyoto Gene-Encyclopedia and genomic analyses were conducted for the mRNAs differentially expressed under high phosphorus. RT-qPCR results confirmed that the expression of RUNX2, BMP2 and osteocalcin in HP group exhibited significant increases than in control group (<i>p</i> &lt; .05). VSMC in HP group also showed higher intracellular calcium content. Volcano plots results show that 379 mRNAs and 728 lncRNAs different expressed in HP group. LncRNA-mRNA co-expression networks analysis revealed that 8 lncRNAs were the most highly connected lncRNAs. Quantitative analysis indicated that two lncRNAs were confirmed to increase significantly in the HP group. The mRNA expression of NT5E and ICAM1 were higher in group HP, while MAP3K7CL was lower than CON group (<i>p</i> &lt; .05). This study provided a working list of lncRNAs that may be relevant to osteogenic differentiation, which presents a new insights into the mechanism of vascular calcification induced by high phosphorus in VSMCs.