Molecular Mechanisms of Diabetic Kidney Disease

Rico-Fontalvo, Jorge; Aroca, Gustavo; Cabrales, José; Daza-Arnedo, Rodrigo; Yánez, Tomás Rodríguez; Martínez‐Ávila, María Cristina; Uparella-Gulfo, Isabella; Raad-Sarabia, María

doi:10.3390/ijms23158668

Cited by 42 publications

(41 citation statements)

References 71 publications

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“…Diabetic nephropathy (DN) is one of the most frequent and severe chronic complications of diabetes, characterized by persistent high albuminuria and a subsequent decline in the glomerular filtration rate [ 1 , 2 ]. The changes in kidney function are associated with specific histopathological findings in glomerular and tubulointerstitial compartments, with renal cell hyperplasia and hypertrophy, the thickening of glomerular and tubular basement membranes and the expansion of tubulointerstitial and mesangial compartments [ 3 , 4 ]. It is well established that patients suffering from both type 1 and type 2 diabetes develop nephropathic complications very early in the progression of the disease; thus, the identification of subjects at risk of DN is required to provide appropriate therapy and slow down evolution towards end-stage renal disease [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Dimuccio

Bellucci²,

Genta³

et al. 2022

IJMS

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Diabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney’s physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition.

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Section: Introductionmentioning

confidence: 99%

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Dimuccio

Bellucci²,

Genta³

et al. 2022

IJMS

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“…The fundamental role of the complement system is the innate immune defense, assuming a protective function against viruses and bacteria that it recognizes as pathogens, in turn promoting inflammation, due to its participation in the elimination of atypical cells that the body identifies as targets to be eliminated. Two main mechanisms are believed to explain the involvement of complement in the development of DKD, some of these are summarized in the Table 1 [6,8,17] .…”

Section: The Role Of Complement In Diabetic Kidney Diseasementioning

confidence: 99%

“…The classic and global vision of DKD has placed it as a noninflammatory glomerular disease, directing its pathogenesis towards the classic pathways of hemodynamic and metabolic alterations as the cornerstone of its clinical course. However, this vision is limited by the recent discoveries and advances in the understanding of the immune response and especially inflammation as a central phenomenon in the development and evolution of the disease [6] .…”

Section: Introductionmentioning

confidence: 99%

The Role of Complement Cascade in Diabetic Kidney Disease: New Paradigms and Therapeutic Targets

Rico-Fontalvo

Aroca-Martínez

Daza-Arnedo³

et al. 2022

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Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus. DKD is a frequent entity, which occurs in approximately 30-40% of diabetic patients. Traditionally, DKD has been considered a non-inflammatory glomerular disease, being perceived as a condition induced primarily by metabolic and hemodynamic changes. Inflammation has been classified as a main phenomenon for the onset and progression of DKD. Today, the inclusion of the inflammatory component is fundamental for the comprehension of the onset and development of this disease. The inflammatory component has multiple pathways, within which the activation and regulation of the complement system is of particular interest. The mechanisms by which complement is part of the multiple inflammatory pathways in DKD are being increasingly understood, which will guide the development of strategies and therapeutic targets.

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“…En consecuencia, esta entidad se presenta en pacientes con DM y compromiso de la función renal y puede ser explicada por varias causas (3,4). El término Nefropatía diabética (ND), se utiliza exclusivamente para señalar las lesiones renales originadas por lesión microangiopática o de los pequeños vasos.…”

Section: Introductionunclassified

Update on diabetic kidney disease

Rico-Fontalvo

Jiménez

Yánez

et al. 2022

An. Fac. Cienc. Méd. (Asunción)

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Enfermedad renal diabética: puesta al díaUpdate on diabetic kidney disease EDUCACIÓN MÉDICA CONTINUA RESUMEN Introducción: La Diabetes Mellitus es una enfermedad inflamatoria sistémica de alta prevalencia e incidencia a nivel mundial. Dentro de las complicaciones crónicas, la enfermedad renal diabética es una de las más frecuentes y que marca el pronóstico. Objetivos: El objetivo de este artículo es hacer una revisión actualizada de la enfermedad renal diabética, a la luz de los cambios en los paradigmas que se han generado en los últimos años con respecto a sus nuevas definiciones, el papel de la inflamación en su desarrollo, la gestión del riesgo cardiovascular y los nuevos tratamientos. La enfermedad renal diabética puede presentarse en aproximadamente el 30-40% de la población con diabetes mellitus tipo 1 o 2 alrededor del mundo. En la patogénesis y progresión de esta condición se distinguen tres ejes fundamentales el hemodinámico, metabólico e inflamatorio. Es importante siempre hacer gestión del riesgo cardiovascular. El diagnóstico se debe hacer con el cálculo de la tasa de filtrado glomerular y la relación albuminuria / creatinuria en muestra ocasional. Los objetivos en el tratamiento deben ser: el control metabólico, reducir o enlentecer la progresión de la enfermedad renal y disminuir los desenlaces cardiovasculares. Conclusión: El tratamiento de la ERD debe ser holístico, desde intervenciones no farmacológicas, como la modificación de los estilos de vida, hasta los nuevos medicamentos como el uso de inhibidores SGLT-2, Agonistas del receptor GLP-1 y el uso antagonista selectivos del receptor mineralocorticoide como finerenone. El futuro es promisorio.

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Molecular Mechanisms of Diabetic Kidney Disease

Cited by 42 publications

References 71 publications

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

The Role of Complement Cascade in Diabetic Kidney Disease: New Paradigms and Therapeutic Targets

Update on diabetic kidney disease

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