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Pathophysiology of the Diabetic Kidney
Open accessAbstract
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.
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Bickel, C. A., Verbalis, J. G., Knepper, M. A., & ECELBARGER, C. A. (2001) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.2001.281.4.f639 · Cited by 107
Komers, R., Lindsley, J. N., Oyama, T., Allison, K. M., & Anderson, S. (2000) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.2000.279.3.f573 · Cited by 107
Self-citationThe cyclin kinase inhibitor p21WAF1, CIP1 is increased in experimental diabetic nephropathy
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Mechanical stretch induces podocyte hypertrophy in vitro1
Petermann, A. T., Pippin, J. W., Durvasula, R. V., Pichler, R. H., Hiromura, K., Monkawa, T., Couser, W. G., & Shankland, S. J. (2004) · Kidney International · doi:10.1111/j.1523-1755.2005.00066.x · Cited by 106
Enhanced expressions of sodium–glucose cotransporters in the kidneys of diabetic Zucker rats
Tabatabai, N. M., Sharma, M., Blumenthal, S. S., & Petering, D. H. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.11.003 · Cited by 106
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Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment
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The tubular hypothesis of nephron filtration and diabetic kidney disease
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Self-citationDeep representation learning of electronic health records to unlock patient stratification at scale
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Jha, R., Lopez-Trevino, S., Kankanamalage, H. R., & Jha, J. C. (2024) · Biomedicines · doi:10.3390/biomedicines12051098 · Cited by 144
Metadata
- Authors
- Vallon, V., & Komers, R.
- Venue
- Comprehensive Physiology
- Publisher
- Wiley
- Published
- 2011-07
- Volume
- 1
- Issue
- 3
- Pages
- 1175-1232
- ISSN
- 2040-4603 (ISSN-L)
- OpenAlex
- W1540594287
- Cited by
- 259
- References
- 665
- Type
- other
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.