دورية أكاديمية
T-Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes.
| العنوان: | T-Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes. |
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| المؤلفون: | Forbes, J.M., McCarthy, D.A., Kassianos, A.J., Baskerville, T., Fotheringham, A.K., Giuliani, K.T.K., Grivei, A., Murphy, A.J., Flynn, M.C., Sullivan, M.A., Chandrashekar, P., Whiddett, R., Radford, K.J., Flemming, N., Beard, S.S., D'Silva, N., Nisbet, J., Morton, A., Teasdale, S., Russell, A. |
| المصدر: | http://dx.doi.org/10.2337/db20-1081Test. |
| بيانات النشر: | American Diabetes Association |
| سنة النشر: | 2021 |
| المجموعة: | The University of Adelaide: Digital Library |
| مصطلحات موضوعية: | Kidney, Humans, Diabetic Nephropathies, Diabetes Mellitus, Type 1, Blood Glucose, Kidney Function Tests, Glomerular Filtration Rate, Retrospective Studies, Adolescent, Adult, Female, Male, Young Adult, Hepatitis A Virus Cellular Receptor 1 |
| الوصف: | Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes (n = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA1c 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m2) and 10-year historical uACR, HbA1c, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in apolipoprotein E-/- mice. Kidney biopsies were used to examine infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACRAUC0-10yrs, 29.7 ± 8.8 vs. 4.5 ± 0.5; P < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m2 higher estimated glomerular filtration rates (modified Schwartz equation; Padj < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; P < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes showed elevated collagen IV and sodium-glucose cotransporter 2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0012-1797 1939-327X |
| العلاقة: | http://purl.org/au-research/grants/nhmrc/GNT1102935Test; http://purl.org/au-research/grants/nhmrc/GNT1160428Test; Diabetes, 2021; 70(August):1754-1766; https://hdl.handle.net/2440/132638Test; Couper, J. [0000-0003-4448-8629] |
| DOI: | 10.2337/db20-1081 |
| الإتاحة: | https://doi.org/10.2337/db20-1081Test https://hdl.handle.net/2440/132638Test |
| حقوق: | © 2021 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https:// www.diabetesjournals.org/content/license. |
| رقم الانضمام: | edsbas.A19B0378 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00121797 1939327X |
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| DOI: | 10.2337/db20-1081 |