IL33/ST2 Axis in Diabetic Kidney Disease: A Literature Review

Interleukin-33 (IL-33) is a cytokine belonging to the IL-1 family, playing a role in inflammatory, infectious and autoimmune diseases and expressed in the cellular nucleus in several tissues. High levels of IL-33 are expressed in epithelial barrier tissues and endothelial barriers. ST2 is a receptor for IL-33, expressed selectively on a subset of Th2 cells, mediating some of their functions. The IL-33/ST2 axis plays an important role in several acute and chronic inflammatory diseases, including asthma and rheumatoid arthritis. Different disorders are related to the activity of IL-33, ST2, or their axis, including cardiovascular disease or renal disturbances. Therefore, in the present work, a literature review was conducted, covering the period from 1 January 2000 to 30 November 2018, in PubMed, ScienceDirect, and Google Scholar database, to assess the involvement of the IL-33/ST2 axis in diabetic kidney disease. 6 articles directly dealing with the argument were identified, highlighting a clear link between IL-33/ST2 axis and diabetic kidney disease or related nephropathy. Overall, the involvement of ST2 seems to be more predictive than IL-33, especially in investigating the deterioration of kidney function; however, both compounds are pivotal in the field of renal diseases. Future studies are required to confirm the scientific evidences on larger and more heterogeneous cohorts.

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Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

Journal of Clinical Medicine ◽

10.3390/jcm10102046 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2046

Author(s):

Goren Saenz-Pipaon ◽

Saioa Echeverria ◽

Josune Orbe ◽

Carmen Roncal

Keyword(s):

Kidney Disease ◽

Extracellular Vesicles ◽

Diabetic Kidney Disease ◽

Current Knowledge ◽

Developed Countries ◽

Disease Diagnosis ◽

Renal Diseases ◽

Diabetic Kidney ◽

Glucose Levels ◽

Stage Renal Disease

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.

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Utility values in diabetic kidney disease: a literature review

Current Medical Research and Opinion ◽

10.1185/03007995.2015.1041895 ◽

2015 ◽

Vol 31 (7) ◽

pp. 1271-1282 ◽

Cited By ~ 8

Author(s):

Tessa Kennedy-Martin ◽

Rosirene Paczkowski ◽

Sharon Rayner

Keyword(s):

Kidney Disease ◽

Literature Review ◽

Diabetic Kidney Disease ◽

Diabetic Kidney ◽

Utility Values

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Elevated Serum Levels of Carbohydrate Antigen 72–4 in Diabetic Kidney Disease

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1532-4576 ◽

2021 ◽

Author(s):

Lei Shi ◽

Jiali Meng ◽

Bin Zhang ◽

Jiandong Chen ◽

Jianzhong Chen ◽

...

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Elevated Serum ◽

Serum Levels ◽

Carbohydrate Antigen ◽

Urinary Albumin ◽

Renal Diseases ◽

Diabetic Patients ◽

Healthy Controls ◽

Diabetic Kidney

AbstractThe aim of this study was to determine whether carbohydrate antigen 72–4 (CA72–4) is elevated in diabetic kidney disease (DKD), and examine the association between urinary albumin-to-creatinine ratio (UACR) and CA72–4 in patients with type 2 diabetes mellitus (T2DM). Non-dialysis patients with T2DM (n=296) and 90 healthy controls were recruited in this study. CA72–4 level was measured by electrochemiluminescence immunoassay. DKD was defined as UACR≥ 30 mg/g in the absence of a urinary infection or other renal diseases. We found that patients with DKD had significantly higher serum CA72–4 levels compared to those with normoalbuminuria and healthy controls. Positive rates of CA72–4 increased gradually and markedly from normoalbuminuria to microalbuminuria and to macroalbuminuria in diabetic patients (7.5, 11.2, and 17.4%, respectively; P for trend< 0.05). CA72–4 also showed a positive correlation with UACR (r=0.288, P< 0.01). Logistic regression analysis revealed the association of increased UACR with an increased odds ratio of elevation of CA72–4 levels (P for trend< 0.05) after multivariable adjustment. In conclusion, serum levels of CA72–4 increase abnormally with the increase in urinary albumin excretion, which affects the specificity of diagnosis of malignancies. An appropriate interpretation of CA72–4 is essential to prevent unnecessary and even hazardous diagnostic procedures in patients with T2DM.

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Phenotypes of diabetic kidney disease (literature review and own data)

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY ◽

10.22141/2224-0721.16.3.2020.205277 ◽

2020 ◽

Vol 16 (3) ◽

pp. 265-271

Author(s):

I.O. Tsaryk ◽

N.V. Pashkovska

Keyword(s):

Kidney Disease ◽

Literature Review ◽

Diabetic Kidney Disease ◽

Diabetic Kidney

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Relationship between lysosomal dyshomeostasis and progression of diabetic kidney disease

Cell Death and Disease ◽

10.1038/s41419-021-04271-w ◽

2021 ◽

Vol 12 (11) ◽

Author(s):

Man Wu ◽

Minjie Zhang ◽

Yaozhi Zhang ◽

Zixian Li ◽

Xingyu Li ◽

...

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Cell Metabolism ◽

Renal Diseases ◽

Future Research ◽

Lysosomal Function ◽

Diabetic Kidney ◽

Effective Interventions ◽

Proximal Tubular Epithelial Cells ◽

And Function

AbstractLysosomes are organelles involved in cell metabolism, waste degradation, and cellular material circulation. They play a key role in the maintenance of cellular physiological homeostasis. Compared with the lysosomal content of other organs, that of the kidney is abundant, and lysosomal abnormalities are associated with the occurrence and development of certain renal diseases. Lysosomal structure and function in intrinsic renal cells are impaired in diabetic kidney disease (DKD). Promoting lysosomal biosynthesis and/or restoring lysosomal function can repair damaged podocytes and proximal tubular epithelial cells, and delay the progression of DKD. Lysosomal homeostasis maintenance may be advantageous in alleviating DKD. Here, we systematically reviewed the latest advances in the relationship between lysosomal dyshomeostasis and progression of DKD based on recent literature to further elucidate the mechanism of renal injury in diabetes mellitus and to highlight the application potential of lysosomal homeostasis maintenance as a new prevention and treatment strategy for DKD. However, research on screening effective interventions for lysosomal dyshomeostasis is still in its infancy, and thus should be the focus of future research studies. The screening out of cell-specific lysosomal function regulation targets according to the different stages of DKD, so as to realize the controllable targeted regulation of cell lysosomal function during DKD, is the key to the successful clinical development of this therapeutic strategy.

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Long noncoding RNA: an emerging player in diabetes and diabetic kidney disease

Clinical Science ◽

10.1042/cs20190372 ◽

2019 ◽

Vol 133 (12) ◽

pp. 1321-1339 ◽

Cited By ~ 11

Author(s):

Jia Guo ◽

Zhangsuo Liu ◽

Rujun Gong

Keyword(s):

Kidney Disease ◽

Noncoding Rna ◽

Diabetic Kidney Disease ◽

Therapeutic Targets ◽

Developed Countries ◽

Mechanisms Of Action ◽

Renal Diseases ◽

Diabetic Kidney ◽

Definitive Therapy ◽

Novel Therapeutic

AbstractDiabetic kidney disease (DKD) is among the most common complications of diabetes mellitus (DM), and remains the leading cause of end-stage renal diseases (ESRDs) in developed countries, with no definitive therapy yet available. It is imperative to decipher the exact mechanisms underlying DKD and identify novel therapeutic targets. Burgeoning evidence indicates that long non-coding RNAs (lncRNAs) are essential for diverse biological processes. However, their roles and the mechanisms of action remain to be defined in disease conditions like diabetes and DKD. The pathogenesis of DKD is twofold, so is the principle of treatments. As the underlying disease, diabetes per se is the root cause of DKD and thus a primary focus of therapy. Meanwhile, aberrant molecular signaling in kidney parenchymal cells and inflammatory cells may directly contribute to DKD. Evidence suggests that a number of lncRNAs are centrally involved in development and progression of DKD either via direct pathogenic roles or as indirect mediators of some nephropathic pathways, like TGF-β1, NF-κB, STAT3 and GSK-3β signaling. Some lncRNAs are thus likely to serve as biomarkers for early diagnosis or prognosis of DKD or as therapeutic targets for slowing progression or even inducing regression of established DKD. Here, we elaborated the latest evidence in support of lncRNAs as a key player in DKD. In an attempt to strengthen our understanding of the pathogenesis of DKD, and to envisage novel therapeutic strategies based on targeting lncRNAs, we also delineated the potential mechanisms of action as well as the efficacy of targeting lncRNA in preclinical models of DKD.

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Advanced diabetic kidney disease complicated by acute interstitial nephritis: A case report and literature review

World Academy of Sciences Journal ◽

10.3892/wasj.2021.108 ◽

2021 ◽

Vol 3 (4) ◽

Author(s):

Jin He ◽

Shubei Chen ◽

Weihong Huang

Keyword(s):

Case Report ◽

Kidney Disease ◽

Literature Review ◽

Interstitial Nephritis ◽

Diabetic Kidney Disease ◽

Acute Interstitial Nephritis ◽

Diabetic Kidney

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The endoplasmic reticulum stress response and diabetic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00021.2011 ◽

2011 ◽

Vol 300 (5) ◽

pp. F1054-F1061 ◽

Cited By ~ 86

Author(s):

Robyn Cunard ◽

Kumar Sharma

Keyword(s):

Endoplasmic Reticulum ◽

Stress Response ◽

Kidney Disease ◽

Er Stress ◽

Diabetic Kidney Disease ◽

Protein Translation ◽

Renal Diseases ◽

Unfolded Proteins ◽

Diabetic Kidney ◽

Er Stress Response

The endoplasmic reticulum (ER) folds and modifies proteins; however, during conditions of cellular stress, unfolded proteins accumulate in the ER and activate the unfolded protein response (UPR). The UPR, also referred to as the ER stress response, activates three distinct signaling cascades that are designed to globally reduce transcription and translation. The three major arms of the mammalian UPR include 1) protein kinase RNA (PKR)-like ER kinase (PERK), 2) inositol-requiring protein-1 (IRE1α), and 3) activating transcription factor-6 (ATF6) pathways. The PERK pathway rapidly attenuates protein translation, whereas the ATF6 and IRE1α cascades transcriptionally upregulate ER chaperone genes that promote proper folding and ER-associated degradation (ERAD) of proteins. This integrated response in turn allows the folding machinery of the ER to catch up with the backlog of unfolded proteins. The ER stress response plays a role in a number of pathophysiological processes, including pancreatic β-cell failure and apoptosis. The goals of the current review are to familiarize investigators with cellular and tissue activation of this response in the rodent and human diabetic kidney. Additionally, we will review therapeutic modulators of the ER stress response and discuss their efficacy in models of diabetic kidney disease. The ER stress response has both protective and deleterious features. A better understanding of the molecular pathways regulated during this process in a cell- and disease-specific manner could reveal novel therapeutic strategies in chronic renal diseases, including diabetic kidney disease.

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