Limitations of CA125 as an Index of Peritoneal Mesothelial Cell Mass

Abstract

Background: CA125 is commonly used as an index of the mesothelial cell mass in patients treated with peritoneal dialysis. However, we have no data that show a direct relationship between the number of mesothelial cells, their functional properties, and the amount of CA125 produced in these cells. Methods: Experiments were performed on primary in vitro cultures of human peritoneal mesothelial cells obtained from 32 donors of various ages and of both sexes. Spontaneous release of CA125 from the confluent mesothelial cells was measured and correlated with the number of cells in monolayers and with their functional properties. We also studied acute effects of cytokines (IL-1β, TNF-α, and INF-γ) and the chronic effects of glucose (45 mM) on the CA125 content in mesothelial cells and the release of this antigen from their cytosol. Results: Cells from older donors released more CA125, but we found no correlation between the number of cells and the amount of CA125 released from their cytosol. The synthesis of CA125 in mesothelial cells does not correlate with the amount of monocyte chemoattractant protein 1 or interleukin-6 produced in these cells. Acute exposure to cytokines did not modify CA125 content or its release from mesothelial cells. Chronic exposure of mesothelial cells for 4 weeks to glucose (45 mM) decreased the CA125 content of their cytosol and the release of this antigen into the culture medium. Mannitol, at the same concentration and under the same conditions, did not produce these effects, namely a decrease in the CA125 content in the cytosol or its release into the cultural medium. Conclusions: The amount of CA125 released from mesothelial cells is not a good index of their number or their functional properties, because the CA125 release depends not only on the number of cells, but also on their properties. Furthermore, the process is affected by the age of the cell donor and environmental factors such as a high glucose content. The results of this study show the limitations of CA125 as an index of the mesothelial cell mass and viability.

Evaluation of Peritoneal Transport and Membrane Status in Peritoneal Dialysis: Focus on Incident Fast Transporters

“…CA-125 is usually measured in solution biocompatibility studies, and it was also recommended as a tool for longitudinal membrane status evaluation. Although Breborowicz et al [27] reported limitations of CA-125 as an index of peritoneal mesothelial cell mass[,] they demonstrated a reduction of CA-125 secretion and expression with chronic exposure to glucose solutions. VEGF is spontaneously produced by cultured human mesothelial cells [21], but also by a variety of other cells, like vascular smooth muscle cells [28].…”

Peritoneal Membrane Evaluation in Routine Clinical Practice

“…Although this has been recently questioned [31] , the finding of low levels of effluent CA125 in long-term PD, notably with UFF make it worthwhile to be routinely measured, in order to clarify its predictive value. It was not the purpose of this study to investigate the relationship between mesothelial cell mass and peritoneal transport: an indirect role has recently been suggested but this seems to vary in short-and long-term PD, possibly mediated earlier by production of vasoactive factors [32][33][34] or later trough epithelial-mesenchymal transition [35] .…”

CA125: Holy Grail or a Poisoned Chalice

“…If one does a simple calculation of appearance rates comparing published rates in patients (which are remarkably similar between studies) with those of Bręborowicz et al [6] and other in vitro studies, then the rate of production in vitro is some 10–30 times higher. Whilst measurements in different matrices (tissue culture medium vs. effluent) might explain a small difference, there are clearly differences between a clean in vitro setup and the uremic peritoneal cavity exposed to both glucose-based dialysis solutions and intercurrent or episodic inflammation.…”

“…These data on the ‘regulation’ of secretion, however, were at odds with both pre-existing and subsequently produced data suggestive of induction of CA125 by pro-inflammatory cytokines [4, 5]. In the current issue, Bręborowicz et al fan the flames of this debate further by suggesting, based exclusively on in vitro data, that CA125 production by peritoneal mesothelial cells neither correlates with, nor is regulated by pro-inflammatory cytokines [6]. …”

“…Interestingly. Bręborowicz et al [6] do show that chronic exposure of mesothelial cells to glucose specifically reduces mesothelial cell CA125 secretion and expression. Since glucose is the major osmotic agent used in PD fluids, this may in part help us to understand why its production in vivo is suppressed and that more biocompatible solutions increase its levels [9,10,11].…”