Persistent Hematuria and Kidney Disease Progression in IgA Nephropathy: A Cohort Study

Yu, Ge-Ping; Guo, Ling; Dong, Jinpei; Shi, Sufang; Liu, Lijun; Wang, Jinwei; Sui, Gui-li; Zhou, Xu‐jie; Xing, Ying; Li, Haixia; Lv, Jicheng; Zhang, Hong

doi:10.1053/j.ajkd.2019.11.008

Cited by 63 publications

(48 citation statements)

References 35 publications

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“…IgAN is considered as primary renal disease worldwide and elucidates 20% to 47% of primary glomerular disease ( Wyatt and Julian, 2013 , Rodrigues et al, 2017 ). It has essentially been described by hypertension, proteinuria, hematuria, and renal dysfunction ( Yu et al, 2020 ). IgAN is most common in Pacific and East Asian than Africans ( Rodrigues et al, 2017 ) and considered as major cause of last-stage kidney disease.…”

Section: Discussionmentioning

confidence: 99%

Construction of miRNA-mRNA network for the identification of key biological markers and their associated pathways in IgA nephropathy by employing the integrated bioinformatics analysis

Fatima

Saleem

Aslam

et al. 2021

Saudi Journal of Biological Sciences

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Background About half-century ago, Immunoglobulin A nephropathy (IgAN) was discovered as a complicated disease with frequent clinical symptoms. Until now, exact mechanism underlying the pathogenesis of IgAN is poorly known. Therefore, current study was aimed to understand the molecular mechanism of IgAN by identifying the key miRNAs and their targeted hub genes. The key miRNAs might contribute to the diagnosis and therapy of IgAN, and could turn out to be a new star in the field of IgAN. Methods The microarray datasets were downloaded from Gene Expresssion Omnibus (GEO) database and analyzed using R package (LIMMA) in order to obtain differential expressed genes (DEGs). Then, the hub genes were identified using cytoHubba plugin of cytoscpae tool and other bioinformatics approaches including protein-protein interaction (PPI) network analysis, module analysis, and miRNA-hub gene network construction was also performed. Results A total of 348 DEGs were identified, of which 107 were upregulated genes and 241 were downregulated genes. Subsequently, the 12 overlapped genes were predicted from cytoHubba, and considered as hub genes. Moreover, a network among miRNA-hub genes was created to explore the correlation between the hub genes and their targeted miRNAs. Network construction ultimately lead to the identification of nine gene named FN1, EGR1, FOS, JUN, SERPINE1, MMP2, ATF3, MYC, and IL1B and one novel key miRNA namely, has-miR-144-3p as biomarker for diagnosis and therapy of IgAN. Conclusion This study updates the information and yield a new perspective in context of understanding the pathogenesis and development of IgAN. In future, key miRNAs might be capable of improving the personalized detection and therapies for IgAN. In vivo and in vitro investigation of miRNAs and pathway interaction is essential to delineate the specific roles of the novel miRNAs, which may help to further reveal the mechanisms underlying IgAN.

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Section: Discussionmentioning

confidence: 99%

Construction of miRNA-mRNA network for the identification of key biological markers and their associated pathways in IgA nephropathy by employing the integrated bioinformatics analysis

Fatima

Saleem

Aslam

et al. 2021

Saudi Journal of Biological Sciences

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“…Calcium and phosphorus metabolism disorders are typical in patients with CKD and are associated with mortality in patients undergoing maintenance dialysis [ 14 , 20–22 ]. IgA nephropathy is the major cause of kidney failure requiring KRT [ 10 , 23–25 ]. However, the roles of calcium and phosphorus metabolism disorders in kidney disease progression in patients with IgA nephropathy who are not undergoing dialysis are still not well established.…”

Section: Discussionmentioning

confidence: 99%

Serum phosphorus and calcium levels, and kidney disease progression in immunoglobulin A nephropathy

Cheng

Jiang

et al. 2021

Clinical Kidney Journal

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Background and objectives Disorders of calcium and phosphorus metabolism have been reported to be associated with all-cause and cardiovascular mortality in patients requiring long-term dialysis therapy. However, its role in disease progression is not well established in patients without dialysis, especially in IgA nephropathy. We aim to evaluate the association of serum phosphorus and calcium and progression of IgA nephropathy. Design, setting, participants and measurements We assessed 2567 patients with IgA nephropathy at The First Affiliated Hospital, College of Medicine, Zhejiang University. Serum phosphorus and calcium were collected at the time of kidney biopsy and each visit. The associations of serum phosphorus, serum calcium with composite kidney disease progression events, defined as 50% eGFR decline and kidney failure were examined using Cox models and restricted cubic splines. Results During a median follow-up of 31.9 months, 248 (10%) patients reached composite kidney disease progression events. A linear relationship was observed between serum phosphorus and composite kidney disease progression events. With the higher levels of phosphorus, the risk of kidney disease progression events increased (Hazard ration [HR], 3.54; 95% CI, 1.37-9.12; P = 0.009. Compared to first quartile group, the HR of kidney disease progression events were 1.66 (0.91-301) for second quartile, 1.67 (0.91-3.08) for the third and 2.62 (1.44-4.77) for the fourth (P for trend =0.002). The association between serum phosphorus and kidney disease progression was detectable (HR, 8.94; 95% CI, 2.33-34.21; P = 0.001) within the subgroup with eGFR < 60 mL/min/1.73 m2, but not among patients with eGFR ≥ 60 mL/min/1.73 m2 (HR, 0.87; 95% CI, 0.17-4.44; P = 0.87). After adjusted for traditional risk factors, higher level of serum calcium was not associated with kidney disease progression events (HR, 0.33; 95%CI, 0.10-1.09). Conclusion Higher serum phosphorus rather than serum calcium was independently associated with kidney disease progression in IgA nephropathy.

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“…In addition, Chemouny et al has reported that antibiotics, depleting gut microbiota e ciently, could ameliorate clinicopathological changes in humanized mice with IgAN [21]. As for the reason why we thought that the modi cation of gut microbiota was associated with the progression of IgAN, previous studies have reported that the higher levels of proteinuria and hematuria could serve as biomarkers of poor prognosis, which could guide the treatment [22,23]. Therefore, it was reasonable to speculate that modi cation of gut microbiota might be correlated with poor prognosis since we indicated that a signi cantly higher abundance of Escherichia-Shigella and a markedly lower abundance of Bi dobacterium spp.…”

Section: Discussionmentioning

confidence: 93%

Modifications of abundances of some bacteria are associated with the severity of IgA nephropathy in Chinese population

Zhong

Tan

et al. 2020

Preprint

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Abstract Background Immunoglobulin A nephropathy (IgAN) is a common autoimmune glomerular disease, the classic manifestations of which are hematuria and proteinuria. The pathogenesis of IgAN has been associated with dysregulated intestinal mucosal immunity. However, whether gut microbial modifications play a part in IgAN remains unclear. Methods Blood and fecal samples were collected from 52 IgAN patients and 25 healthy controls (HCs). The gut microbiome was analyzed by 16S ribosomal RNA (rRNA) gene sequencing, followed by analyses of gut microbiota composition. Furthermore, the levels of galactose-deficient IgA1 (Gd-IgA1), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP), intercellular adhesion molecule-1 (ICAM-1), and C-reactive protein (CRP) was quantified by enzyme-linked immunosorbent assay (ELISA). Results Substantial differences in gut microbiota were found between IgAN patients and HCs (P < 0.05). The abundance of pathogenic bacteria (Bacteroides and Escherichia-Shigella) was significantly higher in IgAN patients than in HCs, while that of beneficial strains (Bifidobacterium and Blautia spp.) was lower. Higher proportions of Escherichia-Shigella and lower proportions of Bifidobacterium spp. were observed in IgAN patients with a high urine RBC count (≥ 10/HP) and proteinuria (≥ 1 g/24 h) levers. Spearman’s correlation analysis was used to assess the association between gut microbiota and biomarkers in IgAN patients. The results showed that the genus Prevotella 7 was negatively correlated with Gd-IgA1, LBP, sCD14, and ICAM-1, while Bifidobacterium spp. presented a significant inverse relationship with LBP and Gd-IgA1. Additionally, Escherichia-Shigella was negatively correlated with Prevotella 7. Conclusions In IgAN patients, gut modifications were characterized by an increase in the numbers of pathogenic bacteria and a reduction in the levers of beneficial bacteria. Our results suggest that disturbance of the intestinal microflora might play a critical part in the severity of IgAN, and may be a potential therapeutic target.

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Persistent Hematuria and Kidney Disease Progression in IgA Nephropathy: A Cohort Study

Cited by 63 publications

References 35 publications

Construction of miRNA-mRNA network for the identification of key biological markers and their associated pathways in IgA nephropathy by employing the integrated bioinformatics analysis

Construction of miRNA-mRNA network for the identification of key biological markers and their associated pathways in IgA nephropathy by employing the integrated bioinformatics analysis

Serum phosphorus and calcium levels, and kidney disease progression in immunoglobulin A nephropathy

Modifications of abundances of some bacteria are associated with the severity of IgA nephropathy in Chinese population

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