Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease.
The current view of diabetic kidney disease, based on meticulously acquired ultrastructural morphometry and the utility of measuring plasma creatinine and urinary albumin, has been almost entirely focused on the glomerulus. While clearly of great importance, changes in the glomerulus are not the major determinant of renal prognosis in diabetes and may not be the primary event in the development of diabetic kidney disease either. Indeed, advances in biomarker discovery and a greater appreciation of tubulointerstitial histopathology and the role of tubular hypoxia in the pathogenesis of chronic kidney disease have given us pause to reconsider the current "glomerulocentric" paradigm and focus attention on the proximal tubule that by virtue of the high energy requirements and reliance on aerobic metabolism render it particularly susceptible to the derangements of the diabetic state. Such findings raise important issues for therapeutic advances specifically targeting the pathophysiological perturbations that develop in this part of the nephron.
Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada richard.gilbert@utoronto.ca.
Richard E
RE
Gilbert
D017209:Apoptosis; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005355:Fibrosis; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000503:physiopathology