Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease

Khanijou, Vuthi; Zafari, Neda; Coughlan, Melinda T.; MacIsaac, Richard J; Ekinci, Elif I

doi:10.1002/dmrr.3556

Cited by 17 publications

(12 citation statements)

References 167 publications

(484 reference statements)

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“…KIM-1, a transmembrane glycoprotein of proximal tubular epithelial cells of the kidney, cannot be detected when the kidney is structurally or functionally normal, but it can be significantly upregulated with tubular damage. Therefore, KIM-1 can be used as a potential biomarker for proximal tubule injury ( 20 ). B2M is a small subunit of major histocompatibility class I molecules that exists in all nucleated cells.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

Zhou

Lin²,

Yang³

et al. 2023

Front. Immunol.

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BackgroundThe study aimed to identify core biomarkers related to diagnosis and immune microenvironment regulation and explore the immune molecular mechanism of diabetic nephropathy (DN) through bioinformatics analysis.MethodsGSE30529, GSE99325, and GSE104954 were merged with removing batch effects, and different expression genes (DEGs) were screened at a criterion |log2FC| >0.5 and adjusted P <0.05. KEGG, GO, and GSEA analyses were performed. Hub genes were screened by conducting PPI networks and calculating node genes using five algorithms with CytoHubba, followed by LASSO and ROC analysis to accurately identify diagnostic biomarkers. In addition, two different GEO datasets, GSE175759 and GSE47184, and an experiment cohort with 30 controls and 40 DN patients detected by IHC, were used to validate the biomarkers. Moreover, ssGSEA was performed to analyze the immune microenvironment in DN. Wilcoxon test and LASSO regression were used to determine the core immune signatures. The correlation between biomarkers and crucial immune signatures was calculated by Spearman analysis. Finally, cMap was used to explore potential drugs treating renal tubule injury in DN patients.ResultsA total of 509 DEGs, including 338 upregulated and 171 downregulated genes, were screened out. “chemokine signaling pathway” and “cell adhesion molecules” were enriched in both GSEA and KEGG analysis. CCR2, CX3CR1, and SELP, especially for the combination model of the three genes, were identified as core biomarkers with high diagnostic capabilities with striking AUC, sensitivity, and specificity in both merged and validated datasets and IHC validation. Immune infiltration analysis showed a notable infiltration advantage for APC co-stimulation, CD8+ T cells, checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation in the DN group. In addition, the correlation analysis showed that CCR2, CX3CR1, and SELP were strongly and positively correlated with checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation in the DN group. Finally, dilazep was screened out as an underlying compound for DN analyzed by CMap.ConclusionsCCR2, CX3CR1, and SELP are underlying diagnostic biomarkers for DN, especially in their combination. APC co-stimulation, CD8+ T cells, checkpoint, cytolytic activity, macrophages, MHC class I, and parainflammation may participate in the occurrence and development of DN. At last, dilazep may be a promising drug for treating DN.

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Section: Discussionmentioning

confidence: 99%

“…B2M is a small subunit of major histocompatibility class I molecules that exists in all nucleated cells. B2M is fully filtered at the glomerulus and then almost completely reabsorbed in the proximal tubule ( 20 ). NAG is a hydrolase widely distributed in organs.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

Zhou

Lin²,

Yang³

et al. 2023

Front. Immunol.

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“…2 For instance, it has been shown that inflammatory markers have the most promise as warning signs of diabetic kidney disease (DKD). 3 Consequently, Nglycosylation of plasma IgG might contribute to pathophysiological processes of type 2 diabetes complications as glycosylation is known to influence IgG effector functions. 4 We therefore hypothesised that N-glycosylation of IgG may be involved in the development of complications of type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…It has been demonstrated that inflammation plays a key role in the pathophysiology of type 2 diabetes and its complications 2 . For instance, it has been shown that inflammatory markers have the most promise as warning signs of diabetic kidney disease (DKD) 3 . Consequently, N‐ glycosylation of plasma IgG might contribute to pathophysiological processes of type 2 diabetes complications as glycosylation is known to influence IgG effector functions 4 .…”

Section: Introductionmentioning

confidence: 99%

IgG N‐glycans are associated with prevalent and incident complications of type 2 diabetes

Memarian

Heijmans

Slieker

et al. 2023

Diabetes Metabolism Res

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Aims/HypothesisInflammation is important in the development of type 2 diabetes complications. The N‐glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N‐glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N‐glycosylation of IgG may be related to the development of complications of type 2 diabetes.MethodsIn three independent type 2 diabetes cohorts, plasma IgG N‐glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N‐glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox‐ and logistic regression, followed by meta‐analyses. The models were adjusted for age and sex and additionally for clinical risk factors.ResultsIgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex.ConclusionsWe showed that IgG N‐glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro‐ and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N‐glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.

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“…Mononuclear cell infiltration into the tubulointerstitium can cause progressive tissue remodelling and chronic inflammation that can lead to interstitial fibrosis and tubular atrophy (Niedermeier et al., 2009). Although TNFRs and MCP‐1 are inflammatory markers (Khanijou et al., 2022), their correlation with TIF during CKD suggests potential use as biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and prognostic biomarkers for tubulointerstitial fibrosis

Rende

Guller

Goldys

et al. 2023

The Journal of Physiology

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Renal fibrosis is the final common pathophysiological pathway in chronic kidney disease (CKD) regardless of the underlying cause of kidney injury. Tubulointerstitial fibrosis (TIF) is considered to be the key pathological predictor of CKD progression. Currently, the gold‐standard tool to identify TIF is kidney biopsy, an invasive method that carries risks. Non‐invasive diagnostics rely on an estimation of glomerular filtration rate and albuminuria to assess kidney function, but these fail to diagnose early CKD accurately or to predict progressive decline in kidney function. In this review, we summarize the current and emerging molecular biomarkers that have been studied in various clinical settings and in animal models of kidney disease and that are correlated with the degree of TIF. We examine the potential of these biomarkers to diagnose TIF non‐invasively and to predict disease progression. We also examine the potential of new technologies and non‐invasive diagnostic approaches in assessing TIF. Limitations of current and potential biomarkers are discussed and knowledge gaps identified.

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Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease

Cited by 17 publications

References 167 publications

Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

Identification of a novel immune landscape signature as effective diagnostic markers related to immune cell infiltration in diabetic nephropathy

IgG N‐glycans are associated with prevalent and incident complications of type 2 diabetes

Diagnostic and prognostic biomarkers for tubulointerstitial fibrosis

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