The tubular hypothesis of nephron filtration and diabetic kidney disease
| العنوان: | The tubular hypothesis of nephron filtration and diabetic kidney disease |
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| المؤلفون: | Volker Vallon, Scott C. Thomson |
| المصدر: | Nat Rev Nephrol |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, Kidney Glomerulus, 030232 urology & nephrology, Renal function, Nephron, Nitric Oxide, Article, 03 medical and health sciences, Sodium-Glucose Transporter 1, 0302 clinical medicine, Chlorides, Sodium-Glucose Transporter 2, Glomerular Filtration Barrier, Internal medicine, Diabetes Mellitus, medicine, Humans, Diabetic Nephropathies, Sodium-Glucose Transporter 2 Inhibitors, Cellular Senescence, Tubuloglomerular feedback, Inflammation, urogenital system, business.industry, Reabsorption, Sodium, Renal Reabsorption, Hypertrophy, Nephrons, Fibrosis, Glucose, Kidney Tubules, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Diabetes Mellitus, Type 2, Nephrology, Macula densa, business, Glomerular hyperfiltration, Glomerular Filtration Rate |
| الوصف: | Kidney size and glomerular filtration rate (GFR) often increase with the onset of diabetes, and elevated GFR is a risk factor for the development of diabetic kidney disease. Hyperfiltration mainly occurs in response to signals passed from the tubule to the glomerulus: high levels of glucose in the glomerular filtrate drive increased reabsorption of glucose and sodium by the sodium–glucose cotransporters SGLT2 and SGLT1 in the proximal tubule. Passive reabsorption of chloride and water also increases. The overall capacity for proximal reabsorption is augmented by growth of the proximal tubule, which (alongside sodium–glucose cotransport) further limits urinary glucose loss. Hyperreabsorption of sodium and chloride induces tubuloglomerular feedback from the macula densa to increase GFR. In addition, sodium–glucose cotransport by SGLT1 on macula densa cells triggers the production of nitric oxide, which also contributes to glomerular hyperfiltration. Although hyperfiltration restores sodium and chloride excretion it imposes added physical stress on the filtration barrier and increases the oxygen demand to drive reabsorption. Tubular growth is associated with the development of a senescence-like molecular signature that sets the stage for inflammation and fibrosis. SGLT2 inhibitors attenuate the proximal reabsorption of sodium and glucose, normalize tubuloglomerular feedback signals and mitigate hyperfiltration. This tubule-centred model of diabetic kidney physiology predicts the salutary effect of SGLT2 inhibitors on hard renal outcomes, as shown in large-scale clinical trials. |
| تدمد: | 1759-507X 1759-5061 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e7d15e1110f3748a0ccad8c181c41fe6Test https://doi.org/10.1038/s41581-020-0256-yTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e7d15e1110f3748a0ccad8c181c41fe6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1759507X 17595061 |
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