Renal expression of cytokines and chemokines in diabetic nephropathy

Araújo, Liliane Silvano; Torquato, Bianca Gonçalves Silva; Silva, Crislaine Aparecida da; Monteiro, Maria Luíza Gonçalves dos Reis; Martins, Ana Luisa Monteiro dos Santos; Silva, Marcos Vinícius da; Reis, Marlene Antônia dos; Machado, Juliana Reis

doi:10.1186/s12882-020-01960-0

Cited by 48 publications

(33 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These changes were more evident in those with advanced tubulointerstitial inflammation. A renal expression of eotaxin demonstrated a tendency for negative correlation with eGFR; meanwhile, there were no relationships with the levels of proteinuria [14]. These results are consistent with our findings the higher eotaxin concentrations in patients without albuminuria in the logistic regression model.…”

Section: Discussionsupporting

confidence: 90%

“…Diabetic nephropathy is associated with both systemic and renal inflammation that involves inflammatory cells, cytokines, and growth factors [7][8][9]. In experimental and clinical diabetes, accumulation of inflammatory cells-mostly macrophages-was observed in the renal interstitium [10][11][12], andenhanced expression of pro-inflammatory cytokineswas revealed in the kidneys [13][14][15]. In patients with diabetic nephropathy, interstitial inflammation and fibrosis were found to be histological predictors of ESRD [16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

Климонтов

Korbut

Орлов

et al. 2020

JCM

View full text Add to dashboard Cite

A panel of cytokines and growth factors, mediating low-grade inflammation and fibrosis, was assessed in patients with type 2 diabetes (T2D) and different patterns of chronic kidney disease (CKD). Patients with long-term T2D (N = 130) were classified into four groups: no signs of CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 without albuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m2; albuminuria and eGFR <60 mL/min/1.73 m2. Thirty healthy subjects were acted as control. Twenty-seven cytokines and growth factors were assessed in serum by multiplex bead array assay. Serum hs-CRP, urinary nephrin, podocine, and WFDC2 were measured by ELISA. Patients with T2D showed elevated IL-1Ra, IL-6, IL-17A, G-CSF, IP-10, MIP-1α, and bFGF levels; concentrations of IL-4, IL-12, IL-15, INF-γ, and VEGF were decreased. IL-6, IL-17A, G-CSF, MIP-1α, and bFGF correlated negatively with eGFR; IL-10 and VEGF demonstrated negative associations with WFDC2; no relationships with podocyte markers were found. Adjusted IL-17A and MIP-1α were predictors of non-albuminuric CKD, IL-13 predicted albuminuria with preserved renal function, meanwhile, IL-6 and hsCRP were predictors of albuminuria with eGFR decline. Therefore, albuminuric and non-albuminuric CKD in T2D patients are associated with different pro-inflammatory shifts in the panel of circulating cytokines.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

Климонтов

Korbut

Орлов

et al. 2020

JCM

View full text Add to dashboard Cite

show abstract

“…Studies on obese or diabetic animal models [5,[28][29][30] and clinical trials targeting proinflammatory molecules in diabetic kidney disease (DKD) [5] suggest that proinflammatory cytokines directly contribute to the progression of renal injury. Proinflammatory cytokines and related molecules are upregulated in the glomeruli of individuals with obesity-or diabetes-related kidney disease [31][32][33] and associate with the (h, i) Quantification of glomerular phospho-NF-κB-p65-positive nuclei (h) and number of F4/80-positive cells (i) per glomerular cross-section from 15 glomeruli per mouse. LFD, n = 7; HFD, n = 14; HFD-AdipoRon, n = 13-14.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin receptor agonist AdipoRon ameliorates renal inflammation in diet-induced obese mice and endotoxin-treated human glomeruli ex vivo

et al. 2021

View full text Add to dashboard Cite

Aims/hypothesis Chronic low-grade inflammation with local upregulation of proinflammatory molecules plays a role in the progression of obesity-related renal injury. Reduced serum concentration of anti-inflammatory adiponectin may promote chronic inflammation. Here, we investigated the potential anti-inflammatory and renoprotective effects and mechanisms of action of AdipoRon, an adiponectin receptor agonist. Methods Wild-type DBA/2J mice were fed with high-fat diet (HFD) supplemented or not with AdipoRon to model obesity-induced metabolic endotoxaemia and chronic low-grade inflammation and we assessed changes in the glomerular morphology and expression of proinflammatory markers. We also treated human glomeruli ex vivo and human podocytes in vitro with AdipoRon and bacterial lipopolysaccharide (LPS), an endotoxin upregulated in obesity and diabetes, and analysed the secretion of inflammatory cytokines, activation of inflammatory signal transduction pathways, apoptosis and migration. Results In HFD-fed mice, AdipoRon attenuated renal inflammation, as demonstrated by reduced expression of glomerular activated NF-κB p65 subunit (NF-κB-p65) (70%, p < 0.001), TNFα (48%, p < 0.01), IL-1β (51%, p < 0.001) and TGFβ (46%, p < 0.001), renal IL-6 and IL-4 (21% and 20%, p < 0.05), and lowered glomerular F4/80-positive macrophage infiltration (31%, p < 0.001). In addition, AdipoRon ameliorated HFD-induced glomerular hypertrophy (12%, p < 0.001), fibronectin accumulation (50%, p < 0.01) and podocyte loss (12%, p < 0.001), and reduced podocyte foot process effacement (15%, p < 0.001) and thickening of the glomerular basement membrane (18%, p < 0.001). In cultured podocytes, AdipoRon attenuated the LPS-induced activation of the central inflammatory signalling pathways NF-κB-p65, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38-MAPK) (30%, 36% and 22%, respectively, p < 0.001), reduced the secretion of TNFα (32%, p < 0.01), and protected against podocyte apoptosis and migration. In human glomeruli ex vivo, AdipoRon reduced the LPS-induced secretion of inflammatory cytokines IL-1β, IL-18, IL-6 and IL-10. Conclusions/interpretation AdipoRon attenuated the renal expression of proinflammatory cytokines in HFD-fed mice and LPS-stimulated human glomeruli, which apparently contributed to the amelioration of glomerular inflammation and injury. Mechanistically, based on assays on cultured podocytes, AdipoRon reduced LPS-induced activation of the NF-κB-p65, JNK and p38-MAPK pathways, thereby impelling the decrease in apoptosis, migration and secretion of TNFα. We conclude that the activation of the adiponectin receptor by AdipoRon is a potent strategy to attenuate endotoxaemia-associated renal inflammation. Graphical abstract

show abstract

“…12 In contrast with our initial hypothesis of lower levels of cytokines/chemokines after SGLT2 inhibition, ertugliflozin was associated with an increase in plasma levels of eotaxin-1, a chemokine that has been found to be elevated in patients with DKD. 35 Ertugliflozin was not associated with significant changes in other markers of inflammation, fibrosis, oxidative stress, or endothelial dysfunction. Insufficient power and/or observation time may have limited our ability to detect a significant reduction in these other markers of inflammation.…”

Section: Discussionmentioning

confidence: 87%

Markers of Kidney Injury, Inflammation, and Fibrosis Associated With Ertugliflozin in Patients With CKD and Diabetes

Liu

Sridhar

Lovblom

et al. 2021

Kidney International Reports

View full text Add to dashboard Cite

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve cardiovascular and kidney outcomes through mechanisms that are incompletely understood. In this exploratory post hoc analysis of the VERTIS RENAL Q2 trial, we report the association between the SGLT2 inhibitor ertugliflozin and markers of kidney injury, inflammation, and fibrosis in participants with type 2 diabetes (T2D) and stage 3 chronic kidney disease (CKD).Methods: Participants were randomized to ertugliflozin (5 or 15 mg/d) or placebo, and plasma samples for biomarker analysis were collected at baseline, 26 weeks, and 52 weeks.Results: Ertugliflozin-treated participants had lower plasma levels of kidney injury molecule-1 (KIM-1) at 26 weeks (P ¼ 0.044) and 52 weeks (P ¼ 0.007) and higher eotaxin-1 at 52 weeks (P ¼ 0.007) postrandomization compared with placebo. The change in KIM-1 was not associated with the baseline albumin to creatinine ratio (ACR) or the estimated glomerular filtration rate (eGFR, P interaction > 0.05). Additionally, the change in KIM-1 was positively correlated with the change in ACR in participants treated with ertugliflozin (P ¼ 0.0071). No other significant associations between ertugliflozin and changes in the markers of tubular injury, inflammation, fibrosis, oxidative stress, and endothelial dysfunction were observed. Conclusion:In conclusion, in participants with T2D and stage 3 CKD, ertugliflozin was associated with a sustained lowering of the tubular injury marker KIM-1 regardless of baseline kidney function.

show abstract

Renal expression of cytokines and chemokines in diabetic nephropathy

Cited by 48 publications

References 54 publications

Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

Multiplex Bead Array Assay of a Panel of Circulating Cytokines and Growth Factors in Patients with Albuminuric and Non-Albuminuric Diabetic Kidney Disease

Adiponectin receptor agonist AdipoRon ameliorates renal inflammation in diet-induced obese mice and endotoxin-treated human glomeruli ex vivo

Markers of Kidney Injury, Inflammation, and Fibrosis Associated With Ertugliflozin in Patients With CKD and Diabetes

Contact Info

Product

Resources

About