Cited by 377Chronic Kidney Disease and DiabetesRenal Diseases and GlomerulopathiesAdvanced Glycation End Products research

Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy

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Cooper, M. E.·2001·Diabetologia

Abstract

Diabetic nephropathy seems to occur as a result of an interaction of metabolic and haemodynamic factors. Glucose dependent pathways are activated within the diabetic kidney. These include increased oxidative stress, renal polyol formation and accumulation of advanced glycated end-products. Haemodynamic factors are also implicated in the pathogenesis of diabetic nephropathy and include increased systemic and intraglomerular pressure and activation of various vasoactive hormone pathways including the renin-angiotensin system and endothelin. These haemodynamic pathways, independently and with metabolic pathways, activate intracellular second messengers such as protein kinase C and MAP kinase, nuclear transcription factors such as NF-kappaB and various growth factors such as the prosclerotic cytokine, TGF-beta and the angiogenic, permeability enhancing growth factor, VEGF. These pathways ultimately lead to increased renal albumin permeability and extracellular matrix accumulation which results in increasing proteinuria, glomerulosclerosis and tubulointerstitial fibrosis. Therapeutic strategies involved in the management and prevention of diabetic nephropathy include currently available treatments such as intensified glycaemic control and antihypertensive agents, particularly those which interrupt the renin-angiotensin system. More novel strategies to influence vasoactive hormone action or to inhibit various metabolic pathways such as inhibitors of advanced glycation, specific protein kinase C isoforms and aldose reductase are at present under experimental and clinical investigation. It is predicted that multiple therapies will be required to reduce the progression of diabetic nephropathy.

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Crossref · 10.1007/s001250100000

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  • DKD is considered to occur as a result of an interplay between metabolic and hemodynamic factors.

    “DKD is considered to occur as a result of an interplay between metabolic and hemodynamic factors (58), with many of the putative pathways leading to injury having already been delineated (59).”

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Authors
Cooper, M. E.
Affiliations
The University of Melbourne (AU)
Corresponding author
Cooper, M. E.
Venue
Diabetologia
Published
2001-11-01
Volume
44
Issue
11
Pages
1957-1972
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
OpenAlex
W1991427290
Cited by
375
References
14
Citations by year
2026: 5 · 2025: 4 · 2024: 10 · 2023: 14 · 2022: 5 · 2021: 19 · 2020: 16 · 2019: 9 · 2018: 8 · 2017: 15 · 2016: 13 · 2015: 10 · 2014: 23 · 2013: 20 · 2012: 14
FWCI
4.27
Type
journal article
Language
en
Open access
Locations
  • Diabetologia (publishedVersion)
  • PubMed (publishedVersion)
Funders
Kidney Health Australia
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Keywords
diabetic nephropathy, metabolic factors, oxidative stress, advanced glycation end products, intraglomerular pressure, renin-angiotensin system, endothelin, protein kinase C, mitogen-activated protein kinase, NF-κB, TGF-beta, vascular endothelial growth factor, albumin permeability, extracellular matrix accumulation, glomerulosclerosis, tubulointerstitial fibrosis, proteinuria, aldose reductase inhibitors, renin-angiotensin system inhibitors, antihypertensive therapy, glycemic control, pathogenesis
MeSH terms
Animals, Diabetic Nephropathies, Diabetic Retinopathy, Disease Models, Animal, Hemodynamics

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