Targeting inflammation in diabetic kidney disease: early clinical trials

Perez-Gomez, María Vanessa; Sanchez-Niño, María Dolores; Sanz, Ana B.; Zheng-Lin, Binbin; Martín-Cleary, Catalina; Ruíz-Ortega, Marta; Fernández-Fernández, Beatriz

doi:10.1080/13543784.2016.1196184

Cited by 68 publications

(40 citation statements)

References 105 publications

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“…The growing global impact of DN, together with the recent ongoing clinical trials on novel therapeutic approaches, have increased the need for novel biomarkers that allow an earlier diagnosis of renal involvement. These tools could let early intervention or prediction of therapy response, leading to a personalized therapeutic approach [3,4,23,24]. One of these tools is urine proteomics, which is a promising strategy for predicting rapid disease progression before albuminuria becomes pathological [25].…”

Section: Biomarkers Of Diabetic Nephropathymentioning

confidence: 99%

“…Different anti-inflammatory strategies with beneficial effects in experimental diabetes may also improve T cell responses, including Th17 related effects [24]. In experimental STZ induced DN, mycophenolate mofetil diminished the number of CD4+/IL-17A+ cells in the kidney and suppressed renal T cell proliferation [94].…”

Section: Pharmacological Therapies Interfering With Th17 Immune Respomentioning

confidence: 99%

“…In human mononuclear cells in peripheral blood, sitagliptin, a DPP-4 inhibitor, diminished T cell proliferation and induced a Th cell phenotype switch to a Treg subtype with higher secretion of TGF-β1 and lower IL-17A gene expression [95]. In this regard, DPP-4 inhibitors improved β-cell function and attenuated autoimmunity in type 1 diabetic mice [24]. Immunotherapy with complete Freund's adjuvant reduced the Th17 response and Th17 related cytokine levels in diabetic mice [96].…”

Section: Pharmacological Therapies Interfering With Th17 Immune Respomentioning

confidence: 99%

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Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

Lavoz

Rayego‐Mateos

Orejudo

et al. 2020

JCM

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Chronic kidney disease has become a major medical issue in recent years due to its high prevalence worldwide, its association with premature mortality, and its social and economic implications. A number of patients gradually progress to end-stage renal disease (ESRD), requiring then dialysis and kidney transplantation. Currently, approximately 40% of patients with diabetes develop kidney disease, making it the most prevalent cause of ESRD. Thus, more effective therapies for diabetic nephropathy are needed. In preclinical studies of diabetes, anti-inflammatory therapeutic strategies have been used to protect the kidneys. Recent evidence supports that immune cells play an active role in the pathogenesis of diabetic nephropathy. Th17 immune cells and their effector cytokine IL-17A have recently emerged as promising targets in several clinical conditions, including renal diseases. Here, we review current knowledge regarding the involvement of Th17/IL-17A in the genesis of diabetic renal injury, as well as the rationale behind targeting IL-17A as an additional therapy in patients with diabetic nephropathy.

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Section: Biomarkers Of Diabetic Nephropathymentioning

confidence: 99%

Section: Pharmacological Therapies Interfering With Th17 Immune Respomentioning

confidence: 99%

Section: Pharmacological Therapies Interfering With Th17 Immune Respomentioning

confidence: 99%

See 1 more Smart Citation

Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

Lavoz

Rayego‐Mateos

Orejudo

et al. 2020

JCM

Self Cite

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“…Over the past two decades, advancing knowledge of intra-renal inflammatory pathways and of resident and recruited immune cell populations within the kidneys has unearthed new opportunities for the development of mechanistically informed, anti-inflammatory therapies for kidney disease (Kurts et al, 2013). More recently, evidence has emerged from a small number of clinical trials, that such strategies can be effective in slowing the progression of renal functional loss (Perez-Gomez et al, 2016;Menne et al, 2017;Nowak et al, 2017). The goal of this Research Topic was to highlight recent basic, pre-clinical, and clinical progress and opportunities related to the targeting of renal inflammation using drugs and biologic agents by publishing relevant full-length and short original research communications and review articles.…”

Section: Editorial On the Research Topic Innovative Biologics And Drumentioning

confidence: 99%

Editorial: Innovative Biologics and Drugs to Target Renal Inflammation

Griffin

Swaminathan

2020

Front. Pharmacol.

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“…MCP-1 deficiency in diabetic db/db mice resulted in less albuminuria, reduced interstitial macrophage influx, and reduced renal fibrosis [4]. Early clinical trials targeting inflammation in diabetic kidney disease reveal promising results [5]. As has been shown in general and for diabetic nephropathy specifically, the development of fibrosis is largely dependent on initiation by an inflamma-tory response, as has been reviewed by Kanasaki et al [6].…”

Section: Introductionmentioning

confidence: 99%

Endothelial heparan sulfate deficiency reduces inflammation and fibrosis in murine diabetic nephropathy

Talsma

Katta

Ettema

et al. 2018

Laboratory Investigation

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Inflammation plays a vital role in the development of diabetic nephropathy, but the underlying regulatory mechanisms are only partially understood. Our previous studies demonstrated that, during acute inflammation, endothelial heparan sulfate (HS) contributes to the adhesion and transendothelial migration of leukocytes into perivascular tissues by direct interaction with l-selectin and the presentation of bound chemokines. In the current study, we aimed to assess the role of endothelial HS on chronic renal inflammation and fibrosis in a diabetic nephropathy mouse model. To reduce sulfation of HS specifically in the endothelium, we generated Ndst1f/fTie2Cre+ mice in which N-deacetylase/N-sulfotransferase-1 (Ndst1), the gene that initiates HS sulfation modifications in HS biosynthesis, was expressly ablated in endothelium. To induce diabetes, age-matched male Ndst1f/fTie2Cre− (wild type) and Ndst1f/fTie2Cre+ mice on a C57Bl/6J background were injected intraperitoneally with streptozotocin (STZ) (50 mg/kg) on five consecutive days (N = 10–11/group). Urine and plasma were collected. Four weeks after diabetes induction the animals were sacrificed and kidneys were analyzed by immunohistochemistry and qRT-PCR. Compared to healthy controls, diabetic Ndst1f/fTie2Cre− mice showed increased glomerular macrophage infiltration, mannose binding lectin complement deposition and glomerulosclerosis, whereas these pathological reactions were prevented significantly in the diabetic Ndst1f/fTie2Cre+ animals (all three p < 0.01). In addition, the expression of the podocyte damage marker desmin was significantly higher in the Ndst1f/fTie2Cre− group compared to the Ndst1f/fTie2Cre+ animals (p < 0.001), although both groups had comparable numbers of podocytes. In the cortical tubulo-interstitium, similar analyses show decreased interstitial macrophage accumulation in the diabetic Ndst1f/fTie2Cre+ animals compared to the diabetic Ndst1f/fTie2Cre− mice (p < 0.05). Diabetic Ndst1f/fTie2Cre+ animals also showed reduced interstitial fibrosis as evidenced by reduced density of αSMA-positive myofibroblasts (p < 0.01), diminished collagen III deposition (p < 0.001) and reduced mRNA expression of collagen I (p < 0.001) and fibronectin (p < 0.001). Our studies indicate a pivotal role of endothelial HS in the development of renal inflammation and fibrosis in diabetic nephropathy in mice. These results suggest that HS is a possible target for therapy in diabetic nephropathy.

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Targeting inflammation in diabetic kidney disease: early clinical trials

Cited by 68 publications

References 105 publications

Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

Editorial: Innovative Biologics and Drugs to Target Renal Inflammation

Endothelial heparan sulfate deficiency reduces inflammation and fibrosis in murine diabetic nephropathy

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