Fig. 4: Lysine treatment directly targets the proximal tubule.

A Urinary albumin/creatinine ratio of short-term (24 h) lysine treated D/SS rats on a normal salt diet (n ≥ 5 animals per group). B Lysine blocks albumin uptake in the proximal tubule cells (OK cell culture) (right panel; green F-actin, magenta fluorescent-labeled albumin). Dose-response showed the inhibition of proximal tubule cell albumin uptake by different lysine concentrations (n ≥ 3 independent cell cultures per group), error bar = SD. C In vivo imaging of protein casts and albumin endocytosis by dual photon microscopy. Albumin is labeled red and both protein plaques and failed endocytosis can be visualized in hypertensive D/SS rats. D Lysine supplement prevents proximal tubule injury in D/SS rats on a high salt diet. Reduction of tissue damage and protein plugs with lysine. Substantial reduction in megalin abundance (LRP2) in dilated proximal tubules can be restored by lysine supplementation. The presence of KIM-1 on the proximal tubule apical membrane shows severe kidney injury in the hypertensive rat on 14D HS (8% NaCl). In contrast, the group supplemented with lysine had a significant reduction in KIM-1 staining. The scale bar is 100 µm; (n = 6 animals per group), error bar = SD. E Lysine proximal tubule metabolism is altered when kidneys are damaged. Different metabolite classes are color-coded. Metabolites changed with q = 0.05 in at least one experiment are depicted. In total, 89 metabolites were significantly altered. F Decrease of free fatty acids in hypertensive kidneys of lysine-treated animals. The boxplot shows a summary of the regulation of 22 quantified free fatty acids (both saturated and unsaturated). G Decrease of sugar metabolites glucose and di-hexose, and increase of NAD in lysine treatment in hypertension. Source data for this figure is available.