Special Issue “Diabetic Nephropathy: Diagnosis, Prevention and Treatment”

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Abstract

Diabetic nephropathy (DN) is the main cause of end-stage renal disease. DN is a complex disease mediated by genetic and environmental factors, and many cellular and molecular mechanisms are involved in renal damage in diabetes. There are no biomarkers that reflect the severity of the underlying renal histopathological changes and can effectively predict the progression of renal damage and stratify the risk of DN among individuals with diabetes mellitus. Current therapeutic strategies are based on the strict control of glucose and blood pressure levels and, although there are new anti-diabetic drugs, these treatments only retard renal damage progression, being necessary novel therapies. In this Special Issue, there are several comprehensive reviews and interesting original papers covering all these topics, which would be of interest to the growing number of readers of the Journal of Clinical Medicine.

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Inflammatory Targets in Diabetic Nephropathy

Javier Donate-Correa, Desirée Luis-Rodríguez, Ernesto Martín-Núñez … (2020)

One of the most frequent complications in patients with diabetes mellitus is diabetic nephropathy (DN). At present, it constitutes the first cause of end stage renal disease, and the main cause of cardiovascular morbidity and mortality in these patients. Therefore, it is clear that new strategies are required to delay the development and the progression of this pathology. This new approach should look beyond the control of traditional risk factors such as hyperglycemia and hypertension. Currently, inflammation has been recognized as one of the underlying processes involved in the development and progression of kidney disease in the diabetic population. Understanding the cascade of signals and mechanisms that trigger this maladaptive immune response, which eventually leads to the development of DN, is crucial. This knowledge will allow the identification of new targets and facilitate the design of innovative therapeutic strategies. In this review, we focus on the pathogenesis of proinflammatory molecules and mechanisms related to the development and progression of DN, and discuss the potential utility of new strategies based on agents that target inflammation.

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Matrix Metalloproteinases in Diabetic Kidney Disease

Nuria García-Fernández, Conxita Jacobs-Cachá, José Mora-Gutiérrez … (2020)

Around the world diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD), which is characterized by mesangial expansion, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. The hallmark of the pathogenesis of DKD is an increased extracellular matrix (ECM) accumulation causing thickening of the glomerular and tubular basement membranes, mesangial expansion, sclerosis, and tubulointerstitial fibrosis. The matrix metalloproteases (MMPs) family are composed of zinc-dependent enzymes involved in the degradation and hydrolysis of ECM components. Several MMPs are expressed in the kidney; nephron compartments, vasculature and connective tissue. Given their important role in DKD, several studies have been performed in patients with DKD proposing that the measurement of their activity in serum or in urine may become in the future markers of early DKD. Studies from diabetic nephropathy experimental models suggest that a balance between MMPs levels and their inhibitors is needed to maintain renal homeostasis. This review focuses in the importance of the MMPs within the kidney and their modifications at the circulation, kidney and urine in patients with DKD. We also cover the most important studies performed in experimental models of diabetes in terms of MMPs levels, renal expression and its down-regulation effect.

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

Carolina Lavoz, Sandra Rayego-Mateos, Macarena Orejudo … (2020)

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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Journal

Journal ID (nlm-ta): J Clin Med

Journal ID (iso-abbrev): J Clin Med

Journal ID (publisher-id): jcm

Title: Journal of Clinical Medicine

Publisher: MDPI

ISSN (Electronic): 2077-0383

Publication date (Electronic): 17 March 2020

Publication date Collection: March 2020

Volume: 9

Issue: 3

Electronic Location Identifier: 813

Affiliations

[1 ]Molecular and Cellular Biology in Renal and Vascular Pathology, IIS-Fundación Jiménez Díaz-UniversidadAutónoma Madrid, 28040 Madrid, Spain; rrodrigues@ 123456fjd.es

[2 ]Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III, 28029 Madrid, Spain

[3 ]Division of Nephrology, School of Medicine, Universidad Austral de Chile, 5090000 Valdivia, Chile; carolina.lavoz@ 123456uach.cl

[4 ]Vascular and Renal Translational Research Group. Institut de Recerca Biomèdica de Lleida (IRBLleida), 25198 Lleida, Spain; srayego@ 123456fjd.es

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[* ]Correspondence: mruizo@ 123456fjd.es

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Marta Ruiz-Ortega https://orcid.org/0000-0002-1495-6535

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Publisher ID: jcm-09-00813

DOI: 10.3390/jcm9030813

PMC ID: 7141346

PubMed ID: 32192024

SO-VID: b0b8acd4-b104-434f-9c0b-a972e9ffec8c

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Special Issue “Diabetic Nephropathy: Diagnosis, Prevention and Treatment”

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Most cited references 11

Inflammatory Targets in Diabetic Nephropathy

Matrix Metalloproteinases in Diabetic Kidney Disease

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

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