Experimental diabetic nephropathy: Is it relevant to the human disease

Darren J. Kelly, Terri J. Allen, Mark E. Cooper

Research output: Contribution to journalReview ArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Diabetic nephropathy is the commonest cause of end-stage renal failure in the western world. It has been suggested that experimental models of diabetic nephropathy can be used to explore the natural history, pathogenesis and role of various treatments in this condition. Experimental diabetic nephropathy is associated with many but not all of the functional and structural abnormalities observed in human diabetic nephropathy, such as increased glomerular filtration rate, renal hypertrophy, albuminuria and glomerular and tubulointerstitial structural abnormalities. Diabetic nephropathy appears to occur as a result of an interplay of haemodynamic and metabolic factors. Haemodynamic factors include not only systemic and intraglomerular hypertension but also alterations in various vasoactive hormones and their receptors, which may act directly or via effects on blood pressure. Glucose dependent pathways have been implicated in diabetic nephropathy with recent studies focussing on advanced glycation end products and protein kinase C activation. Both glucose and haemodynamic dependent pathways activate a range of cytokines, including transforming growth factor-β, which appear to play a pivotal role in mediating renal injury. Interventional studies in experimental models of diabetic nephropathy have emphasized the importance of tight glycaemic control and effective blood pressure reduction. In particular, agents that interrupt the renin-angiotensin system have been shown to be renoprotective but whether they are superior to other anti-hypertensive agents has not been fully clarified. Experimental studies have provided the rationale for a number of clinical trials, which have confirmed the deleterious effects of hyperglycaemia and hypertension on the diabetic kidney. Experimental models of diabetic nephropathy are currently being used to explore more novel compounds which inhibit various pathogenic pathways implicated in the pathogenesis of diabetic nephropathy.

Original languageEnglish
Pages (from-to)177-185
Number of pages9
JournalNephrology
Volume5
Issue number3
DOIs
Publication statusPublished - 27 Dec 2000
Externally publishedYes

Keywords

  • Diabetes
  • Haemodynamic
  • Metabolic
  • Nephropathy
  • Rat growth factors

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