Review article
PATHOPHYSIOLOGICAL FACTORS IN THE DEVELOPMENT OF DIABETIC NEPHROPATHY – NEW INSIGHTS
KRISTINA BLASLOV
orcid.org/0000-0002-9747-8742
; Merkur University Hospital, Vuk Vrhovac Department of Diabetes, Endocrinology and Metabolic Diseases, Zagreb, Croatia
TOMISLAV BULUM
; Merkur University Hospital, Vuk Vrhovac Department of Diabetes, Endocrinology and Metabolic Diseases, Zagreb, Croatia
LEA DUVNJAK
; Merkur University Hospital, Vuk Vrhovac Department of Diabetes, Endocrinology and Metabolic Diseases, Zagreb, Croatia
Abstract
Diabetic nephropathy (DN), also known as Kimmelstiel-Wilson syndrome, is a progressive kidney disease characterized by nephrotic syndrome and diffuse glomerulosclerosis. It affects about 30% of patients with diabetes mellitus and is a prime indication for dialysis in many Western countries as well as in Croatia. Moreover, it takes a high fourth place in total disease cost, thus it is a very important public health problem. Hyperglycemia, dyslipidemia and hypertension are well established risk factors for the disease development and progression. However, nowadays, the knowledge about the pathophysiology of the disease is expanded and recently focused on the role of growth factors. Well balanced local and plasma concentration of growth factors is important for achievement and maintenance of glomerular integrity and function, so any disturbances could be a contributing factor to the development of DN. There is a growing body of literature suggesting that bone morphogenic protein 7 (BMP7), fibroblast growth factor 23 (FGF23) and fibroblast growth factor 21(FGF21) may play an important role in the DN development and progression. BMP7 possesses antifibrotic and proteolytic activity, so it could diminish the action of profibrotic factors and play an inhibitory role in the disease pathogenesis. It has been demonstrated that plasma concentration of BMP7 is decreasing in parallel to the drop in glomerular filtration rate (GFR) and albumin excretion increase. The plasma concentration of FGF21 and FGF23 has been shown to increase in parallel to DN progression. Moreover, they are linked with hyperinsulinemia and insulin resistance as well as with other diabetic complications such as cardiovascular events and endothelial dysfunction and retinopathy conditions closely related to DN. However, the background of the disturbances is not well established; it is not clarified whether GFR lowering causes increase of FGF21 and FGF23 or the increase in FGF21 and FGF23 concentration causes GFR lowering. The loop is yet to be clarified in order to develop a possible novel therapeutic approach in the treatment of this disease with serious consequences for the individual as well as for the entire population.
Keywords
diabetic nephropathy; BMP7; FGF21; FGF23
Hrčak ID:
126805
URI
Publication date:
14.9.2014.
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