title: Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis.
abstract: Residual renal function and the integrity of the peritoneal membrane contribute to morbidity and mortality among patients treated with peritoneal dialysis. Glucose and its degradation products likely contribute to the deterioration of the remnant kidney and damage to the peritoneum. Benfotiamine decreases glucose-induced tissue damage, suggesting the potential for benefit in peritoneal dialysis. Here, in a model of peritoneal dialysis in uremic rats, treatment with benfotiamine decreased peritoneal fibrosis, markers of inflammation, and neovascularization, resulting in improved characteristics of peritoneal transport. Furthermore, rats treated with benfotiamine exhibited lower expression of advanced glycation endproducts and their receptor in the peritoneum and the kidney, reduced glomerular and tubulointerstitial damage, and less albuminuria. Increased activity of transketolase in tissue and blood contributed to the protective effects of benfotiamine. In primary human peritoneal mesothelial cells, the addition of benfotiamine led to enhanced transketolase activity and decreased expression of advanced glycation endproducts and their receptor. Taken together, these data suggest that benfotiamine protects the peritoneal membrane and remnant kidney in a rat model of peritoneal dialysis and uremia.
authors.affiliation: Department of Nephrology, University of Heidelberg, Im Neuenheimer Feld 162, 69120 Heidelberg, Germany. lars.kihm@med.uni-heidelberg.de
authors.forename: Lars P
authors.initials: LP
authors.lastname: Kihm
authors.forename: Sandra
authors.initials: S
authors.lastname: Müller-Krebs
authors.forename: Julia
authors.initials: J
authors.lastname: Klein
authors.forename: Gregory
authors.initials: G
authors.lastname: Ehrlich
authors.forename: Laura
authors.initials: L
authors.lastname: Mertes
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Gross
authors.forename: Antonysunil
authors.initials: A
authors.lastname: Adaikalakoteswari
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.forename: Vedat
authors.initials: V
authors.lastname: Schwenger
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000818:Animals; D005355:Fibrosis; D017127:Glycation End Products, Advanced / Q000032:analysis; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis; D013831:Thiamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014174:Transketolase / Q000378:metabolism; D014511:Uremia / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D042461:Vascular Endothelial Growth Factor A; D014174:Transketolase; D013831:Thiamine; C013835:benphothiamine