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Review
. 2016 Aug;59(8):1616-20.
doi: 10.1007/s00125-016-3995-3. Epub 2016 May 20.

Angiopoietins and Diabetic Nephropathy

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Free PMC article
Review

Angiopoietins and Diabetic Nephropathy

Luigi Gnudi. Diabetologia. .
Free PMC article

Abstract

Diabetic nephropathy is the main cause of end-stage renal failure in the Western world. In diabetes, metabolic and haemodynamic perturbations disrupt the integrity of the glomerular filtration barrier, leading to ultrastructural alterations of the glomeruli, including podocyte foot process fusion and detachment, glomerular basement membrane thickening, reduced endothelial cell glycocalyx, and mesangial extracellular matrix accumulation and glomerulosclerosis, ultimately leading to albuminuria and end-stage renal disease. Many vascular growth factors, such as angiopoietins, are implicated in glomerular biology. In normal physiology angiopoietins regulate the function of the glomerular filtration barrier. When they are dysregulated, however, as they are in diabetes, they drive the cellular mechanisms that mediate diabetic glomerular pathology. Modulation of angiopoietins expression and signalling has been proposed as a tool to correct the cellular mechanisms involved in the pathophysiology of diabetic microvascular disease, such as retinopathy in humans. Future work might evaluate whether this novel therapeutic approach should be extended to diabetic kidney disease.

Keywords: Albuminuria; Angiopoietin; Diabetes; Endothelial cells; Glomerulus; Review.

Figures

Fig. 1
Fig. 1
ANGPT2/ANGPT1 imbalance is paralleled by capillary destabilisation. ANGPT1 is downregulated in early diabetic kidney disease, leading to diabetes-mediated angiopoietin imbalance (ANGPT2 > ANGPT1); ANGPT2 excess results in proteinuria. Repletion of ANGPT1 restores angiopoietin balance (ANGPT1 > ANGPT2) and, acting as a ‘brake’ on vascular lesions, prevents albuminuria and glomerular structural lesions in the early phases of diabetic glomerular disease. Red arrows indicate changes favouring progression towards vascular disease, green arrows point towards changes stimulating a healthy vessel

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