Table 3.

Main relevant pathophysiologic changes per study

Cell/Organ SystemToxinMain Observed Effect
(1) Endothelium
 Dou, 200426ISInhibition proliferation and repair
 Faure, 200628ISIncrease endothelial microparticle release
 Dou, 200727ISInduction ROS, inhibition glutathione
 Ito, 201030ISIncrease endothelial/leukocyte interaction (adhesion)
 Yu, 201133ISInhibition proliferation; increase senescence; increase ROS and decrease NO production
 Itoh, 201229ISInduction ROS
(2) Smooth muscle cells
 Yamamoto, 200651ISIncrease proliferation
 Chitalia, 201346ISGeneration tissue factor (linked to clot formation), tissue factor breakdown retarded
(3) Leukocytes
 Schepers, 200731PCSActivation oxidative burst
 Ito, 201030ISIncrease endothelial/leukocyte interaction (adhesion)
(4) Whole vessels
 Adijang, 200840ISIncrease aortic calcification and stiffness, expression osteoblast markers, and OATs
 Adijang, 201041ISInduction cell senescence
(5) Cardiac cells
 Lekawanvijit, 201035ISCardiomyocyte proliferation, cardiac fibrosis, inflammation
(6) Whole heart
 Yisireyili, 201349ISIncrease cardiomyocyte hypertrophy, cardiac fibrosis, oxidative stress
(7) Renal tubular cells
 Bolati, 201138ISIncrease epithelial-to-mesenchymal transition
 Sun, 201334IS, PCSEnhanced expression cytokine and inflammatory genes
 Sun, 201236IS, PCSActivation RAAS and epithelial-to-mesenchymal transition, fibrosis, nephrosclerosis
 Shimizu, 201237ISIncrease expression MCP-1
 Sun, 201239IS, PCSIncrease Klotho gene methylation, renal fibrosis
 Watanabe, 201245PCSIncrease renal tubular damage
 Shimizu, 201343ISInduction mediators for fibrosis (TGF-β1 and Smad3)
 Shimizu, 201347ISInduction generation adhesion molecule (ICAM-1)
 Bolati, 201350ISIncreased oxidative stress
(8) Whole kidneys
 Adijang, 200840ISIncrease fibrosis
 Shimizu, 201342ISIncrease angiotensinogen expression
(9) Hepatocytes
 Odamaki, 200452ISIncrease albumin production
 Tsujimoto, 201032ISInhibition metabolic clearance losartan
(10) Intestinal cells
 Tsujimoto, 201248ISInhibition pumps involved in clearance of pravastatin
(11) Adipocytes
 Koppe, 201344PCSIncrease insulin resistance, decrease lipogenesis, increase lipolysis, ectopic lipid redistribution
  • IS, indoxyl sulfate; ROS, reactive oxygen species; NO, nitric oxide; PCS, p-cresyl sulfate; OATs, organic anion transporters; RAAS, renin angiotensin aldosterone system; MCP-1, monocyte endothelial chemotactic protein-1; TGF-β1, transforming growth factor-β1; ICAM-1, intercellular adhesion molecule-1.