Indoxyl Sulphate Retention Is Associated with Microvascular Endothelial Dysfunction after Kidney Transplantation

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 3640
• Main Authors: Hobson, Sam, Arefin, Samsul, Rahman, Awahan, Hernandez, Leah, Ebert, Thomas, de Loor, Henriette, Evenepoel, Pieter, Stenvinkel, Peter, Kublickiene, Karolina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Age; Arteries; Belgium; Bioassays; Biomarkers; Blood pressure; Body mass index; Bradykinin; Calcification; Cardiovascular disease; Cardiovascular Diseases; Care and treatment; chronic kidney disease; Chronic kidney failure; Comparative analysis; Coronary vessels; Dialysis; EndoPAT; endothelial dysfunction; Endothelium; Endothelium, Vascular - metabolism; Germany; Health aspects; Health care industry; Humans; Hyperemia; Indican - metabolism; indoxyl sulphate; Investigations; Kidney diseases; kidney transplantation; Kidney Transplantation - adverse effects; Kidney transplants; Kidneys; Medicin och hälsovetenskap; Microvasculature; Mortality; Nitric oxide; Nitroprusside - pharmacology; Oxidative stress; P-selectin; Pharmaceutical industry; Quality of Life; Regression analysis; Renal Insufficiency, Chronic - therapy; Risk factors; Stiffness; Sulfates; Sweden; Toxins; Transplantation; United Kingdom; Vascular Diseases - metabolism; Vascular Diseases - pathology; United Kingdom; Sweden; Belgium; Germany; chronic kidney disease; nitric oxide; kidney transplantation; EndoPAT; indoxyl sulphate; p-cresyl sulphate; vessel stiffness; endothelial dysfunction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043640

Kidney transplantation (KTx) is the preferred form of renal replacement therapy in chronic kidney disease (CKD) patients, owing to increased quality of life and reduced mortality when compared to chronic dialysis. Risk of cardiovascular disease is reduced after KTx; however, it is still a leading cause of death in this patient population. Thus, we aimed to investigate whether functional properties of the vasculature differed two years post-KTx (postKTx) compared to baseline (time of KTx). Using the EndoPAT device in 27 CKD patients undergoing living-donor KTx, we found that vessel stiffness significantly improved while endothelial function worsened postKTx vs. baseline. Furthermore, baseline serum indoxyl sulphate (IS), but not p-cresyl sulphate, was independently negatively associated with reactive hyperemia index, a marker of endothelial function, and independently positively associated with P-selectin postKTx. Finally, to better understand the functional effects of IS in vessels, we incubated human resistance arteries with IS overnight and performed wire myography experiments ex vivo. IS-incubated arteries showed reduced bradykinin-mediated endothelium-dependent relaxation compared to controls via reduced nitric oxide (NO) contribution. Endothelium-independent relaxation in response to NO donor sodium nitroprusside was similar between IS and control groups. Together, our data suggest that IS promotes worsened endothelial dysfunction postKTx, which may contribute to the sustained CVD risk.