Non-invasive assessment of peritoneal membrane alterations




peritoneal dialysis, peritoneal cells, peritoneal effluent, gene expressioon, CA 125, interleukin-6, PAI-1, peritoneal membrane


The peritoneal dialysis membrane is subject to remodelling in the course of peritoneal dialysis. In the absence of longitudinal morphological studies, this process is mainly studied indirectly by the investigation of changes in peritoneal transport. Non-invasive assessment of the peritoneum is also possible by assessment of substances that originate from peritoneal tissues and can be determined either as their gene expression in peritoneal effluent cells and/or as proteins in peritoneal effluent. Three of these biomarkers will be discussed, because longitudinal data are available.

Cancer antigen 125 (CA 125) is present on the mesothelium,while its gene (MUC 16) is expressed in peritoneal effluent cells and is related to dialysate CA 125 protein. The constitutive production and the small intra-individual variability of 15% indicate its usefulness as a follow-up marker of mesothelial cell mass. Dialysate appearance rate is higher on biocompatible than on conventional solutions, but both decrease during long-term follow-up.

Interleukin-6 (Il-6) is present in peritoneal effluent due to both transport from the circulation and local intraperitoneal production. Its appearance rate is unrelated to its gene expression in peritoneal cells. The intra-individual variation of effluent Il-6 averages 28%, hampering the interpretation of cross-sectional values. The relationships between effluent Il-6 and peritoneal transport have been interpreted as microinflammation, but are difficult to interprete due to mathematical coupling.

Plasminogen activator inhibitor-1 (PAI-1) is encoded by the SERPINE 1 gene. A relationship is present between effluent concentration and gene expression. PAI-1 production is stimulated by glucose. PAI-1 appearance rate increases with PD duration. The sensitivity of effluent PAI-1 for the diagnosis of encapsulating peritoneal sclerosis was 100% one year prior to the diagnosis and the specificity 56%.

It can be concluded that the discussed biomarkers are useful extensions to transport in assessment of the peritoneum during dialysis.



Krediet RT, Struijk DG. Peritoneal changes in patients on long-term peritoneal dialysis. Nat Rev Nephrol 2013;9:419-429.

Coester AM, Smit W, Struijk DG et al. Longitudinal analysis of fluid transport and their determinants in PD patients. Perit Dial Int 2014;34:195-203.

Taranu T, Florea L, Paduraru D et al. Morphological changes of the peritoneal membrane in patients with long-term dialysis. Rom J Morphol Embryol 2014:55:927-932.

Honda K, Nitta K, Horita S et al. Morphological changes in the peritoneal vasculature of patients on CAPD with ultrafiltration failure. Nephron 1996;72:171-176.

Williams JD, Craig KJ,Topley N et al. Morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol 2002;13:470-479.

Mateijsen MAM, van der WAL AC, Hendriks PMEM et al. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis. Perit Dial Int 1999;19:517-525.

Sherif AM, Nakayama M, Mauyama Y et al. Quantitative assessment of the peritoneal vessel density and vasculopathy in CAPD patients. Nephrol Dial Transplant 2006;21:1675-1681.

Del Peso G, Jimenez-Heffernan JA, Bajo MA et al. Epithelial- to –mesenchymal transition of mesothelial cells is an early event during peritoneal dialysis and is associated with high peritoneal transport. Kidney Int 2008; 73:S26-S33.

Kabawat SE, Bast RC Bhan AK et al. Tissue distribution of a coelomic -epithelium-related antigen recognized by the monoclonal antibody OC125. Int J Gynecol Pathol 1983;2:275-285.

Visser CE, Brouwer-Steenbergen JJE, Betjes MGH et al. Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal dialysis patients. Nephrol Dial Transplant 1995;10:64-69.

Sanussi AA, Zweers MM, Weening JJ et al. Expression of cancer antigen 125 by peritoneal mesothelial cells is not influenced by the duration of peritoneal dialysis. Perit Dial Int 2001;21:495-500.

Ho-dac-Pannekeet MM, Hiralall JK, Struijk DG et al. Longitudinal follow-up of CA 125 in peritoneal effluent. Kidney Int 1997;51:888-893.

Lopes Barreto D, Coester AM, Noordzij M et al. Variability of effluent cancer antigen 125 and interleukin-6 determination in peritoneal dialysis patients. Nephrol Dial Transplant 2011;26:3739-3744.

Parikova A, Hrubra P, Krejcik Z et al. Peritoneal dialysis induces alterations in the transcriptome of peritoneal cells before detectible peritoneal functional changes. Am J Physiol Renal Physiol 2020;318:F229-F237.

Pannekeet MM, Zemel D, Koomen GCM et al. Dialysate markers of peritoneal tissue during peritonitis and in stable CAPD. Perit Dial Int 1995;15:217-225.

Rippe B, Simonsen O, Heimburger O et al. Long-term clinical effects of a peritoneal dialysis fluid with less glucose degradation products. Kidney Int 2001;59:348-357.

Jones S, Holmes C, Krediet RT et al. Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen and decreases hyaluronic acid levels. Kidney Int 2001;59:1529-538.

Williams JD, Topley N, Craig KL et al. The Euro-balance trial: The effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane. Kidney Int 2004;66:408-418.

Le Poole CY, Welten ASA, ter Wee PM et al. A peritoneal dialysis regimen low in glucose and glucose degradation products results in increased cancer antigen 125 and peritoneal activation. Perit Dial Int 2012;32:305-315.

Van Snick J. Interleukin-6; an overview. Annu Rev Immunol 1990;8:253-278.

Topley N, Jorres A, Luttmann W et al. Human peritoneal cells synthesize Il-6; induction by Il-1β and TNFα. Kidney Int 1993;43:226-233.

Gillerot G, Goffin E, Michel C et al. Genetic and clinical factors influence the baseline permeability of the peritoneal membrane. Kidney Int 2005;67:2477-2487.

Lee TY, Tsai, YC, Yang YK et al. Association between between interleukin-10 gene polymorphism-592 (A/C) and peritoneal transport in patients undergoing peritoneal dialysis. Nephrology (Carlton) 2011;16:663-671.

Verduijn M, Marechal C, Coester AM et al. The -174G/C variant of Il-6 as risk factor for mortality and technique failure in a large cohort of peritoneal dialysis patients. Nephrol Dial Transplant 2012;27:3516-3523.

Lambie M, Chess J, Donovan K et al. Independent effects of systemic and peritoneal inflammation on peritoneal dialysis survival. J Am Soc Nephrol 2013;24:2071-2080.

Rodrigues AS, Martins M, Korevaar JC et al. Evaluation of peritoneal transport and membrane status in peritoneal dialysis: focus on incident fast transporters. Am J Nephrol 2007;27:84-91.

Cho Y, Johnson DW, Vesey DA et al. Dialysate interleukin-6 predicts increasing peritoneal solute transport rate in incident peritoneal dialysis patients. BMC Nephrol 2014;15:8.

Sampimon DE, Korte MP, Lopes Barreto et al. Early diagnostic markers for encapsulating peritoneal sclerosis: a case-control study. Perit Dial Int 10;30:163-169.

Lopes Barreto D, Sampimon DE, Struijk DG et al. Early detection of imminent encapsulating peritoneal sclerosos. Free water transport, selected effluent proteins or both. Perit Dial Int 2019;39:83-89.

Lijnen HR. Pleitropic functions of plasminogen activator-1. J Thromb Haemost 2005;3:35-45.

Sakamoto K, Sakamoto T, Ogawa H. Effects of metabolic risk factors on production of plasminogen activator inhibitor-1 and adiponectin by adipocytes. Circ J 2008;72:844-846.

Basurto L, Sanchez L, Diaz A et al. Differences between metabolically healthy and unhealthy obesity in PAI-1 level. Thromb Res 2019;180:110-114. 33. Uchiyama T, Kurabayshi M, Ohyama Y et al. Hypoxia induces transcription of the plasminogen activator-1 gene through genistein-sensitive tyrosine kinase pathways in vascular endothelial cells. Arterioscler Thromb Vasc Biol 2000;20:1155-1161.

Van Westrhenen R, Zweers MM, Kunne C et al. A pyruvate-buffered dialysis fluid induces less peritoneal angiogenesis and fibrosis than a conventional solution. Perit Dial Int 2008;28:487-496.

Dvorak HF, Brown LF, Detmar M et al. Vascular permeability factor/ vascular endothelial growth factor, microvascular permeability, and angiogenesis. Am J Pathol 1995;146:1029-1039.

Rerolle JP, Hertig A, Nguyen G et al. Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis. Kidney Int 2000;58:1841-1850.

Rabieian R, Boshtam M, Zareei M et al. Plasminogen activatot inhibitor type-1 as a regulator of fibrosis. J Cell Biochem 2018;119:17-27.

Mandl-Weber S, Haslinger B, Sitter T. Thrombin upregulates production of plasminogen activator inhibitor type 1 in human peritoneal mesothelial cells.

Perit Dial Int 1999;19: 319-324.

Katsutani M, Ito T, Kohno N et al. N. Glucose-based PD solution, but not icodextrin-based PD solution, induces plasminogen activator inhibitor-1 and tissue-type plasminogen activator in human peritoneal mesothelial cells via ERK1/2. Ther Apher Dial 2007;11:94-100.

Mandl-Weber S, Haslinger B, Schalkwijk et al. Early glycated albumin, but not advanced glycated albumin, methylglyoxal, or 3-deoxyglucosone increases the expression of PAI-1 in human peritoneal mesothelial cells. Perit Dial Int 2001;21:487-494.

Goedde M, Sitter T, Schiffl Het al. Coagulation and fibrinolysis-related antigens in plasma and dialysate of CAPD patients. Perit Dial Int 1997;17:162-166.

Lopes Barreto D, Coester AM, Struijk DG et al. Can effluent matrix metalloproteinase-2 and plasminogen activator inhibitor-1 be used as biomarkers of peritoneal membrane alterations in peritoneal dialysis patients? Perit Dial Int 2013;33:529-537.

Boer AW, Levi M, Reddingius RE et al. Intraperitoneal hypercoagulation and hypofibrinolysis is present in childhood peritonitis. Pediatr Nephrol 199;13:284-287.

Lopes Barreto D, Struijk DG, Krediet RT. Peritoneal effluent MMP-2 and PAI-1 in encapsulating peritoneal sclerosis. Am J Kidney Dis 2015;65:748-75.



How to Cite

Krediet R, Parikova A. Non-invasive assessment of peritoneal membrane alterations. Bull Dial Domic [Internet]. 2020 Aug. 20 [cited 2023 Mar. 28];3(3):119-26. Available from: