Pathophysiology of the Diabetic Kidney
- 1 July 2011
- book chapter
- review article
- Published by Wiley in Comprehensive Physiology
- Vol. 1 (3), 1175-1232
- https://doi.org/10.1002/cphy.c100049
Abstract
Diabetes mellitus contributes greatly to morbidity, mortality, and overall health care costs. In major part, these outcomes derive from the high incidence of progressive kidney dysfunction in patients with diabetes making diabetic nephropathy a leading cause of end‐stage renal disease. A better understanding of the molecular mechanism involved and of the early dysfunctions observed in the diabetic kidney may permit the development of new strategies to prevent diabetic nephropathy. Here we review the pathophysiological changes that occur in the kidney in response to hyperglycemia, including the cellular responses to high glucose and the responses in vascular, glomerular, podocyte, and tubular function. The molecular basis, characteristics, and consequences of the unique growth phenotypes observed in the diabetic kidney, including glomerular structures and tubular segments, are outlined. We delineate mechanisms of early diabetic glomerular hyperfiltration including primary vascular events as well as the primary role of tubular growth, hyperreabsorption, and tubuloglomerular communication as part of a “tubulocentric” concept of early diabetic kidney function. The latter also explains the “salt paradox” of the early diabetic kidney, that is, a unique and inverse relationship between glomerular filtration rate and dietary salt intake. The mechanisms and consequences of the intrarenal activation of the renin‐angiotensin system and of diabetes‐induced tubular glycogen accumulation are discussed. Moreover, we aim to link the changes that occur early in the diabetic kidney including the growth phenotype, oxidative stress, hypoxia, and formation of advanced glycation end products to mechanisms involved in progressive kidney disease. © 2011 American Physiological Society. Compr Physiol 1:1175‐1232, 2011.This publication has 731 references indexed in Scilit:
- Inflammatory signaling and cellular senescenceCellular Signalling, 2009
- Enhanced expressions of sodium–glucose cotransporters in the kidneys of diabetic Zucker ratsDiabetes Research and Clinical Practice, 2009
- Estrogens and the diabetic kidneyGender Medicine, 2008
- Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the ratHistochemistry and Cell Biology, 2008
- What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium?Diabetologia, 2008
- Novel roles of the IGF–IGFBP axis in etiopathophysiology of diabetic nephropathyDiabetes Research and Clinical Practice, 2007
- Angiotensin II induces human TGF-β1 promoter activation: similarity to hyperglycaemiaDiabetologia, 2002
- Comparison of renal hemodynamics in early non-insulin-dependent and insulin-dependent diabetes mellitusJournal of Diabetic Complications, 1991
- Renal function in black Americans with Type II diabetesJournal of Diabetic Complications, 1989
- Renal hypertrophy in experimental diabetes: Some functional aspectsJournal of Diabetic Complications, 1987