TY - JOUR
T1 - Neutral pH and low–glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal dialysis
AU - Schaefer, Betti
AU - Bartosova, Maria
AU - Macher-Goeppinger, Stephan
AU - Sallay, Peter
AU - Vörös, Peter
AU - Ranchin, Bruno
AU - Vondrak, Karel
AU - Ariceta, Gema
AU - Zaloszyc, Ariane
AU - Bayazit, Aysun K.
AU - Querfeld, Uwe
AU - Cerkauskiene, Rimante
AU - Testa, Sara
AU - Taylan, Christina
AU - VandeWalle, Johan
AU - Yap, Yok Chin
AU - Krmar, Rafael T.
AU - Büscher, Rainer
AU - Mühlig, Anne K.
AU - Drozdz, Dorota
AU - Caliskan, Salim
AU - Lasitschka, Felix
AU - Fathallah-Shaykh, Sahar
AU - Verrina, Enrico
AU - Klaus, Günter
AU - Arbeiter, Klaus
AU - Bhayadia, Raj
AU - Melk, Anette
AU - Romero, Philipp
AU - Warady, Bradley A.
AU - Schaefer, Franz
AU - Ujszaszi, Akos
AU - Schmitt, Claus Peter
PY - 2018/8/1
Y1 - 2018/8/1
N2 - © 2018 International Society of Nephrology The effect of peritoneal dialysates with low–glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low–glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low–glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.
AB - © 2018 International Society of Nephrology The effect of peritoneal dialysates with low–glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low–glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low–glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.
KW - chronic kidney disease
KW - peritoneal dialysis
KW - peritoneal membrane
U2 - 10.1016/j.kint.2018.02.022
DO - 10.1016/j.kint.2018.02.022
M3 - Article
SN - 0085-2538
VL - 94
SP - 419
EP - 429
JO - Kidney International
JF - Kidney International
IS - 2
ER -