Schaefer, Betti, Bartosova, Maria, Macher-Goeppinger, Stephan, Sallay, Peter, Voros, Peter, Ranchin, Bruno, Vondrak, Karel, Ariceta, Gema, Zaloszyc, Ariane, Bayazit, Aysun K., Querfeld, Uwe, Cerkauskiene, Rimante, Testa, Sara, Taylan, Christina, VandeWalle, Johan, Yap, YokChin, Krmar, Rafael T., Buescher, Rainer, Muhlig, Anne K., Drozdz, Dorota, Caliskan, Salim ORCID: 0000-0002-3316-8032, Lasitschka, Felix, Fathallah-Shaykh, Sahar, Verrina, Enrico, Klaus, Gunter, Arbeiter, Klaus, Bhayadia, Raj, Melk, Anette, Romero, Philipp, Warady, Bradley A., Schaefer, Franz, Ujszaszi, Akos and Schmitt, Claus Peter (2018). Neutral pH and low-glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal dialysis. Kidney Int., 94 (2). S. 419 - 430. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schaefer, BettiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartosova, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macher-Goeppinger, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sallay, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voros, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ranchin, BrunoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vondrak, KarelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ariceta, GemaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zaloszyc, ArianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bayazit, Aysun K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Querfeld, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cerkauskiene, RimanteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Testa, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taylan, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
VandeWalle, JohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yap, YokChinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krmar, Rafael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buescher, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muhlig, Anne K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drozdz, DorotaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caliskan, SalimUNSPECIFIEDorcid.org/0000-0002-3316-8032UNSPECIFIED
Lasitschka, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fathallah-Shaykh, SaharUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verrina, EnricoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klaus, GunterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arbeiter, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bhayadia, RajUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Melk, AnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romero, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warady, Bradley A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, FranzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ujszaszi, AkosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmitt, Claus PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-177342
DOI: 10.1016/j.kint.2018.02.022
Journal or Publication Title: Kidney Int.
Volume: 94
Number: 2
Page Range: S. 419 - 430
Date: 2018
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1523-1755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TO-MESENCHYMAL TRANSITION; RESIDUAL RENAL-FUNCTION; MESOTHELIAL CELLS; ULTRAFILTRATION FAILURE; SOLUTE TRANSPORT; TRIAL; CONVERSION; SCLEROSIS; EXPOSURE; DISEASEMultiple languages
Urology & NephrologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17734

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