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Diabetic Nephropathy: Diagnosis, Prevention and Treatment

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (25 December 2019) | Viewed by 62152

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Prof. Dr. Marta Ruiz-Ortega

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1. Molecular and Cellular Biology in Renal and Vascular Pathology, IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain
2. Red de Investigación Renal (REDINREN) Madrid, Spain
Interests: renal diseases; cardiovascular diseases; basic research; inflammation; fibrosis
Special Issues, Collections and Topics in MDPI journals

Dr. Raul Rodrigues-Diez

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1. Molecular and Cellular Biology in Renal and Vascular Pathology. IIS-Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain
2. Red de Investigación Renal (REDINREN) Spain, Madrid, Spain
Interests: renal diseases; cardiovascular diseases; basic research; inflammation; fibrosis
Special Issues, Collections and Topics in MDPI journals

Dr. Sandra Rayego-Mateos

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Molecular and Cellular Biology in Renal and Vascular Pathology, IIS-Fundación Jiménez Díaz, Universidad Autónoma Madrid Faculty of Medicine, Madrid, Spain
Interests: renal diseases; cardiovascular diseases; basic research; inflammation; fibrosis
Special Issues, Collections and Topics in MDPI journals

Dr. Carolina Lavoz

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Division of Nephrology, School of Medicine, Universidad Austral, Valdivia, Chile
Interests: renal diseases; cardiovascular diseases; basic research; inflammation; fibrosis

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) is a major health problem, because of its association with high cardiovascular risk and the progression to end-stage renal disease (ESRD) of most patients, requiring dialysis or transplantation. Diabetic nephropathy (DN) is the main cause of ESRD. DN is complex disease mediated by genetic and environmental factors. Initially, DN was considered a metabolic disease, but recent investigations have suggested the involvement of inflammation and immune cells in the pathogenesis of this disease. Recognized therapeutic strategies used in DN patients, including the strict control of glucose levels, blood pressure, and new anti-diabetic drugs, only retard renal damage progression, and there are no novel direct therapies for DN. Importantly, a barrier to progress is the lack of animal models resembling the main features of human DN, and future studies are needed. In addition, there are no biomarkers that reflect the severity of the underlying renal histopathological changes, and that can effectively predict the progression of renal damage and stratify the risk of DN among individuals with diabetes mellitus.

Prof. Dr. Marta Ruiz-Ortega
Dr. Raul Rodrigues-Diez
Dr. Sandra Rayego-Mateos
Dr. Carolina Lavoz
Guest Editors

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Keywords

diabetic nephropathy
inflammation
fibrosis
immune cells
miRNAs
novel therapeutic targets
signaling systems
experimental models
biomarkers

Published Papers (13 papers)

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Editorial

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4 pages, 183 KiB

Open AccessEditorial

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

by Marta Ruiz-Ortega, Raul R. Rodrigues-Diez, Carolina Lavoz and Sandra Rayego-Mateos

J. Clin. Med. 2020, 9(3), 813; https://doi.org/10.3390/jcm9030813 - 17 Mar 2020

Cited by 63 | Viewed by 5370

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. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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13 pages, 949 KiB

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Gender, Albuminuria and Chronic Kidney Disease Progression in Treated Diabetic Kidney Disease

by Beatriz Fernandez-Fernandez, Ignacio Mahillo, Jinny Sanchez-Rodriguez, Sol Carriazo, Ana B. Sanz, Maria Dolores Sanchez-Niño and Alberto Ortiz

J. Clin. Med. 2020, 9(6), 1611; https://doi.org/10.3390/jcm9061611 - 26 May 2020

Cited by 15 | Viewed by 2489

Abstract

Background: Women are reported to have a lower incidence of renal replacement therapy, despite a higher prevalence of chronic kidney disease (CKD). Aim: To analyze diabetic kidney disease (DKD) progression in men and women. Methods: Prospective cohort: n = 261, 35% women, new consecutive nephrology DKD referrals. Results: Women smoked less and better complied with the dietary phosphate and sodium restrictions. Despite a less frequent nephrology referral, women had lower baseline albuminuria. Over a 30 ± 10-month follow-up, albuminuria decreased in women and the estimated glomerular filtration rate (eGFR) loss was slower than in men. However, the percentage of rapid progressors was similar in both sexes. The best multivariate model predicting rapid progression in men (area under curve (AUC) = 0.92) and women differed. Albuminuria and fractional excretion of phosphate (FEphosphate) were part of the men multivariable model, but not of women. The AUC for the prediction of rapid progression by albuminuria was higher in men than in women, and the albuminuria cut-off points also differed. In women, there was a higher percentage of rapid progressors who had baseline physiological albuminuria. Conclusions: Female DKD differs from male DKD: albuminuria was milder and better responsive to therapy, the loss of eGFR was slower and the predictors of rapid progression differed from men: albuminuria was a better predictor in men than in women. Lifestyle factors may contribute to the differences. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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21 pages, 3459 KiB

Open AccessArticle

Urine E-cadherin: A Marker for Early Detection of Kidney Injury in Diabetic Patients

by Michael Koziolek, Gerhard A. Mueller, Gry H. Dihazi, Klaus Jung, Constanze Altubar, Manuel Wallbach, Ivana Markovic, Dirk Raddatz, Olaf Jahn, Hülya Karaköse, Christof Lenz, Henning Urlaub, Abdelhi Dihazi, Abdellatif El Meziane and Hassan Dihazi

J. Clin. Med. 2020, 9(3), 639; https://doi.org/10.3390/jcm9030639 - 27 Feb 2020

Cited by 15 | Viewed by 4188

Abstract

Diabetic nephropathy (DN) is the main reason for end-stage renal disease. Microalbuminuria as the non-invasive available diagnosis marker lacks specificity and gives high false positive rates. To identify and validate biomarkers for DN, we used in the present study urine samples from four patient groups: diabetes without nephropathy, diabetes with microalbuminuria, diabetes with macroalbuminuria and proteinuria without diabetes. For the longitudinal validation, we recruited 563 diabetic patients and collected 1363 urine samples with the clinical data during a follow-up of 6 years. Comparative urinary proteomics identified four proteins Apolipoprotein A-I (APOA1), Beta-2-microglobulin (B2M), E-cadherin (CDH1) and Lithostathine-1-alpha (REG1A), which differentiated with high statistical strength (p < 0.05) between DN patients and the other groups. Label-free mass spectrometric quantification of the candidates confirmed the discriminatory value of E-cadherin and Lithostathine-1-alpha (p < 0.05). Immunological validation highlighted E-cadherin as the only marker able to differentiate significantly between the different DN stages with an area under the curve (AUC) of 0.85 (95%-CI: [0.72, 0.97]). The analysis of the samples from the longitudinal study confirmed the prognostic value of E-cadherin, the critical increase in urinary E-cadherin level was measured 20 ± 12.5 months before the onset of microalbuminuria and correlated significantly (p < 0.05) with the glomerular filtration rate measured by estimated glomerular filtration rate (eGFR). Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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11 pages, 571 KiB

Open AccessArticle

Gla-Rich Protein (GRP) as an Early and Novel Marker of Vascular Calcification and Kidney Dysfunction in Diabetic Patients with CKD: A Pilot Cross-Sectional Study

by Ana P. Silva, Carla S.B. Viegas, Filipa Mendes, Ana Macedo, Patrícia Guilherme, Nelson Tavares, Carolina Dias, Fátima Rato, Nélio Santos, Marília Faísca, Edgar de Almeida, Pedro L. Neves and Dina C. Simes

J. Clin. Med. 2020, 9(3), 635; https://doi.org/10.3390/jcm9030635 - 27 Feb 2020

Cited by 13 | Viewed by 3398

Abstract

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2–4). Spearman’s correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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21 pages, 7654 KiB

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VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy

by Carolina Lavoz, Raul R. Rodrigues-Diez, Anita Plaza, Daniel Carpio, Jesús Egido, Marta Ruiz-Ortega and Sergio Mezzano

J. Clin. Med. 2020, 9(2), 302; https://doi.org/10.3390/jcm9020302 - 21 Jan 2020

Cited by 25 | Viewed by 3464

Abstract

The absence of optimal treatments for Diabetic Nephropathy (DN) highlights the importance of the search for novel therapeutic targets. The vascular endothelial growth factor receptor 2 (VEGFR2) pathway is activated in experimental and human DN, but the effects of its blockade in experimental models of DN is still controversial. Here, we test the effects of a therapeutic anti-VEGFR2 treatment, using a VEGFR2 kinase inhibitor, on the progression of renal damage in the BTBR ob/ob (leptin deficiency mutation) mice. This experimental diabetic model develops histological characteristics mimicking the key features of advanced human DN. A VEGFR2 pathway-activation blockade using the VEGFR2 kinase inhibitor SU5416, starting after kidney disease development, improves renal function, glomerular damage (mesangial matrix expansion and basement membrane thickening), tubulointerstitial inflammation and tubular atrophy, compared to untreated diabetic mice. The downstream mechanisms involved in these beneficial effects of VEGFR2 blockade include gene expression restoration of podocyte markers and downregulation of renal injury biomarkers and pro-inflammatory mediators. Several ligands can activate VEGFR2, including the canonical ligands VEGFs and GREMLIN. Activation of a GREMLIN/VEGFR2 pathway, but not other ligands, is correlated with renal damage progression in BTBR ob/ob diabetic mice. RNA sequencing analysis of GREMLIN-regulated genes confirm the modulation of proinflammatory genes and related-molecular pathways. Overall, these data show that a GREMLIN/VEGFR2 pathway activation is involved in diabetic kidney disease and could potentially be a novel therapeutic target in this clinical condition. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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12 pages, 549 KiB

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The Error of Estimated GFR in Type 2 Diabetes Mellitus

by Sergio Luis-Lima, Tomás Higueras Linares, Laura Henríquez-Gómez, Raquel Alonso-Pescoso, Angeles Jimenez, Asunción María López-Hijazo, Natalia Negrín-Mena, Candelaria Martín, Macarena Sánchez-Gallego, Sara Judith Galindo-Hernández, Raquel Socas Fernández del Castillo, Manuel Castilla-Marrero, Santiago Domínguez-Coello, Vanesa Vilchez de León, Rafael Valcárcel-Lopez, Nerea Insausti-Garmendia, Beatriz Escamilla, Sara Estupiñán, Patricia Delgado-Mallén, Ana-María Armas-Padrón, Domingo Marrero-Miranda, Ana González-Rinne, Rosa María Miquel Rodríguez, María Angeles Cobo-Caso, Laura Díaz-Martín, Federico González-Rinne, Alejandra González-Delgado, Marina López-Martínez, Alejandro Jiménez-Sosa, Armando Torres and Esteban Porrini Show full author list Hide full author list

J. Clin. Med. 2019, 8(10), 1543; https://doi.org/10.3390/jcm8101543 - 26 Sep 2019

Cited by 13 | Viewed by 3134

Abstract

Type 2 diabetes mellitus represents 30–50% of the cases of end stage renal disease worldwide. Thus, a correct evaluation of renal function in patients with diabetes is crucial to prevent or ameliorate diabetes-associated kidney disease. The reliability of formulas to estimate renal function is still unclear, in particular, those new equations based on cystatin-C or the combination of creatinine and cystatin-C. We aimed to assess the error of the available formulas to estimate glomerular filtration rate in diabetic patients. We evaluated the error of creatinine and/or cystatin-C based formulas in reflecting real renal function over a wide range of glomerular filtration rate (from advanced chronic kidney disease to hyperfiltration). The error of estimated glomerular filtration rate by any equation was common and wide averaging 30% of real renal function, and larger in patients with measured glomerular filtration rate below 60 mL/min. This led to chronic kidney disease stages misclassification in about 30% of the individuals and failed to detect 25% of the cases with hyperfiltration. Cystatin-C based formulas did not outperform creatinine based equations, and the reliability of more modern algorithms proved to be as poor as older equations. Formulas failed in reflecting renal function in type 2 diabetes mellitus. Caution is needed with the use of these formulas in patients with diabetes, a population at high risk for kidney disease. Whenever possible, the use of a gold standard method to measure renal function is recommended. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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10 pages, 2069 KiB

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Association between Beta2-Adrenergic Receptor Agonists and the Risk of Vascular Complications in Diabetic Patients: A Population-Based Cohort Study

by Hee Jeong Lee, Haekyung Lee, Song Hee Oh, Suyeon Park, Kwang-Young Jung, Hyoungnae Kim, Soon Hyo Kwon, Jin Seok Jeon, Dong Cheol Han and Hyunjin Noh

J. Clin. Med. 2019, 8(8), 1145; https://doi.org/10.3390/jcm8081145 - 31 Jul 2019

Cited by 4 | Viewed by 3427

Abstract

Beta2-adrenergic receptor (β2AR) agonists can have protective effects targeting macrophage activation, but research on human subjects has not been done. This study was designed to assess the relationship between the use of β2AR agonists and diabetic vascular complications. Using data from the Korean National Health Insurance Service, adults first diagnosed with diabetes in 2004 (n = 249,222) were followed up until 31 December 2015. Propensity score matching was performed between case and control groups (n = 5179 in each), and multivariate analysis was conducted. The β2AR agonist group was divided into quartiles according to the duration of β2AR agonist use. During the follow-up, the incidence of vascular complications gradually decreased as the duration of β2AR agonist administration increased. Multivariate analysis revealed that the hazard ratio for all composite vascular complications was 0.80 (95% CI, 0.75–0.86, p < 0.001) in the longest quartile of β2AR agonist use as compared with the control group after adjusting for confounding variables. The association between the duration of β2AR agonist use and the risk of each vascular complication including cerebrovascular, peripheral vascular, peripheral neural, renal, and ophthalmic complications was consistent, and the risks were significantly lower in the longest users than the control group. Long-term use of β2AR agonists may exert a protective effect against diabetic vascular complications. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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17 pages, 4028 KiB

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Therapeutic Potential of Lespedeza bicolor to Prevent Methylglyoxal-Induced Glucotoxicity in Familiar Diabetic Nephropathy

by Moon Ho Do, Jae Hyuk Lee, Kyohee Cho, Min Cheol Kang, Lalita Subedi, Amna Parveen and Sun Yeou Kim

J. Clin. Med. 2019, 8(8), 1138; https://doi.org/10.3390/jcm8081138 - 31 Jul 2019

Cited by 18 | Viewed by 3619

Abstract

Lespedeza bicolor (LB) is often used in traditional medicine to remove toxins, replenish energy stores, and regulate various symptoms of diabetes. This study aimed to explore the use of LB as a therapeutic to prevent diabetic nephropathy in methylglyoxal (MGO)-treated models in vitro and in vivo. Western blotting, immunostaining, and biochemical assays were used to obtain several experimental readouts in renal epithelial cells (LLC-PK1) and BALB/c mice. These include: production of reactive oxygen species (ROS), formation of advanced glycation end-products (AGEs), expression of receptor for advanced glycation end-products (RAGE), apoptotic cell death, glucose levels, fatty acid and triglyceride levels, expression of pro-inflammatory cytokines IL-1β and TNF-α, glyoxalase 1 (Glo1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Pretreatment with LB significantly reduced MGO-induced cellular apoptosis, intracellular production of ROS, and formation of AGEs to ameliorate renal dysfunction in vitro and in vivo. Interestingly, administering LB in MGO-treated cells and mice upregulated the expression of Nrf2 and Glo1, and downregulated the expression of IL-1β and TNF-α. Moreover, LB reduced MGO-induced AGE accumulation and RAGE expression in the kidneys, which subsequently reduced AGE-RAGE interactions. Overall, LB ameliorates renal cell apoptosis and corrects renal dysfunction in MGO-treated mice. These findings extend our understanding of the pathogenic mechanism of MGO-induced nephrotoxicity and regulation of the AGE/RAGE axis by Lespedeza bicolor. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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12 pages, 6122 KiB

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Detection and Characterization of a Biochemical Signature Associated with Diabetic Nephropathy Using Near-infrared Spectroscopy on Tissue Sections

by Sander De Bruyne, Jo Van Dorpe, Jonas Himpe, Wim Van Biesen, Sigurd Delanghe, Marijn M. Speeckaert and Joris R. Delanghe

J. Clin. Med. 2019, 8(7), 1022; https://doi.org/10.3390/jcm8071022 - 12 Jul 2019

Cited by 15 | Viewed by 3393

Abstract

Histological evaluation of renal biopsies is currently the gold standard for acquiring important diagnostic and prognostic information in diabetic nephropathy (DN) patients. Nevertheless, there is an unmet clinical need for new biomarkers that allow earlier diagnosis and risk stratification. As biochemical changes in tissues must precede any symptomatic or morphological expression of a disease, we explored the potential of near-infrared (NIR) spectroscopy in the detection of a biochemical signature associated with DN. Kidney tissue sections were investigated using NIR spectroscopy, followed by principal component analysis and soft independent modelling of class analogy. A biochemical signature indicative of DN was detected, which enabled perfect discrimination between tissue sections with normal histological findings (n = 27) and sections obtained from DN patients (n = 26). Some spectral changes related to carbamoylation and glycation reactions appeared to be similar to the ones obtained in patients with DN. In addition, treatment with the deglycating enzyme fructosamine-3-kinase resulted in partial to pronounced restorations of the spectral pattern. Significant relationships were found between spectral features and laboratory parameters indicative of glycemic and uremic load, such as hemoglobin A1c, urea, creatinine, estimated glomerular filtration rate, and proteinuria. The presented method could be a useful tool to complement histopathological analysis in order to prevent or delay further disease progression, especially in the setting of post-transplant surveillance kidney biopsies. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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Review

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Matrix Metalloproteinases in Diabetic Kidney Disease

by Nuria Garcia-Fernandez, Conxita Jacobs-Cachá, José María Mora-Gutiérrez, Ander Vergara, Josune Orbe and María José Soler

J. Clin. Med. 2020, 9(2), 472; https://doi.org/10.3390/jcm9020472 - 08 Feb 2020

Cited by 61 | Viewed by 5341

Abstract

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. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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23 pages, 797 KiB

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Inflammatory Targets in Diabetic Nephropathy

by Javier Donate-Correa, Desirée Luis-Rodríguez, Ernesto Martín-Núñez, Víctor G. Tagua, Carolina Hernández-Carballo, Carla Ferri, Ana Elena Rodríguez-Rodríguez, Carmen Mora-Fernández and Juan F. Navarro-González

J. Clin. Med. 2020, 9(2), 458; https://doi.org/10.3390/jcm9020458 - 07 Feb 2020

Cited by 119 | Viewed by 9366

Abstract

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. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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30 pages, 1572 KiB

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The Coming Age of Flavonoids in the Treatment of Diabetic Complications

by Teresa Caro-Ordieres, Gema Marín-Royo, Lucas Opazo-Ríos, Luna Jiménez-Castilla, Juan Antonio Moreno, Carmen Gómez-Guerrero and Jesús Egido

J. Clin. Med. 2020, 9(2), 346; https://doi.org/10.3390/jcm9020346 - 27 Jan 2020

Cited by 56 | Viewed by 7708

Abstract

Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding therapies to prevent or retard the progression of diabetic complications remains an unmet need due to the complexity of mechanisms involved, which include inflammation, oxidative stress and angiogenesis, among others. Flavonoids are natural antioxidant compounds that have been shown to possess anti-diabetic properties. Moreover, increasing scientific evidence has demonstrated their potential anti-inflammatory and anti-oxidant effects. Consequently, the use of these compounds as anti-diabetic drugs has generated growing interest, as is reflected in the numerous in vitro and in vivo studies related to this field. Therefore, the aim of this review is to assess the recent pre-clinical and clinical research about the potential effect of flavonoids in the amelioration of diabetic complications. In brief, we provide updated information concerning the discrepancy between the numerous experimental studies supporting the efficacy of flavonoids on diabetic complications and the lack of appropriate and well-designed clinical trials. Due to the well-described beneficial effects on different mechanisms involved in diabetic complications, the excellent tolerability and low cost, future randomized controlled studies with compounds that have adequate bioavailability should be evaluated as add-on therapy on well-established anti-diabetic drugs. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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17 pages, 1210 KiB

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

by Carolina Lavoz, Sandra Rayego-Mateos, Macarena Orejudo, Lucas Opazo-Ríos, Vanessa Marchant, Laura Marquez-Exposito, Antonio Tejera-Muñoz, Juan F. Navarro-González, Alejandra Droguett, Alberto Ortiz, Jesús Egido, Sergio Mezzano, Raúl R. Rodrigues-Diez and Marta Ruiz-Ortega

J. Clin. Med. 2020, 9(1), 272; https://doi.org/10.3390/jcm9010272 - 19 Jan 2020

Cited by 29 | Viewed by 5988

Abstract

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. Full article

(This article belongs to the Special Issue Diabetic Nephropathy: Diagnosis, Prevention and Treatment)

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