Research Projects

Chronic kidney disease (CKD) is a significant clinical issue in elderly patients, with increased morbidity and mortality rates. Renal fibrosis is often associated with a decrease in the renal membrane of an anti-aging protein called Klotho, which overexpression in transgenic mice can make the disease resistant. As CKD progresses, disturbances in the hypothalamus-pituitary-thyroidal (HPT) axis are also reported, leading to non-thyroidal low T3 syndrome. Klotho regulates various pathways, including phosphate homeostasis, IGF-1, and Wnt signaling. The activation of Wnt/β-catenin and TGF-β/Smad signaling pathways has been linked to the progression of renal fibrosis in CKD. Recent reports suggest a reciprocal relationship between Klotho and both TGF-β/Smad and Wnt signaling, where upregulation of Wnt/β-catenin signaling in the aging and CKD population reduces Klotho levels and vice versa. To investigate how these reciprocal relationships change upon T3 treatment, researchers have identified a plant-derived compound named baicalein that can inhibit Wnt/β-catenin signaling in HEK cells and further increase klotho mRNA expression levels. By using a synergistic combination of T3 and baicalein, a higher and stable upregulation of Klotho levels can be achieved, potentially ameliorating or slowing down the progression of CKD. A renal-specific delivery of T3 and baicalein using Glycol chitosan-based renal docking biopolymeric nano micelles is proposed as part of targeted delivery, safety, and efficacy. This study approach using klotho protein could unite missing links in CKD biology and offer significant advantages for treating CKD and delaying kidney disease progression in the aging population.