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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2003  |  Volume : 14  |  Issue : 4  |  Page : 462-468
Cancer Antigen (CA) 125, a Novel Peritoneal Membrane Marker in CAPD Patients

Renal Unit, Obafemi Awolowo University Teaching Hospitals Complex, PMB 5538 Ile-Ife, Osun State, Nigeria

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Chronic renal failure (CRF) remains a major cause of morbidity and mortality world-wide and consumes substantial percentage of health budgets in the developed countries. Dialysis, in particular, continuous ambulatory peritoneal dialysis (CAPD), as a form of therapy in the management of CRF, has its own side effects and can contribute to the morbidity and mortality. The end result of these side effects is loss of effective surface area consequent on the development of peritoneal sclerosis. Peritoneal sclerosis in CAPD occurs gradually over repeated number of dialysis sessions. Serial observations of changes in the peritoneum, as a dialyzing surface, are difficult and it is only available by peritoneal biopsy, which is an invasive procedure. However, the discovery of some markers in the effluents of CAPD patients as a measure of peritoneal membrane status has reduced the need for this invasive procedure. In particular, the discovery of cancer antigen 125 (CA 125) in the effluent has provided a much-needed tool to follow the changes in peritoneal membrane of CAPD patients and prevent the occurrence of much dreaded peritoneal sclerosis.

Keywords: Chronic renal failure, CAPD, Peritoneal membrane markers, Cancer antigen CA

How to cite this article:
Sanusi A A, Arogundade F A, Akinsola A. Cancer Antigen (CA) 125, a Novel Peritoneal Membrane Marker in CAPD Patients. Saudi J Kidney Dis Transpl 2003;14:462-8

How to cite this URL:
Sanusi A A, Arogundade F A, Akinsola A. Cancer Antigen (CA) 125, a Novel Peritoneal Membrane Marker in CAPD Patients. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2022 Jan 26];14:462-8. Available from: https://www.sjkdt.org/text.asp?2003/14/4/462/32910

   Introduction Top

Chronic renal failure (CRF) is a condition that leaves its sufferers in a state of constant suffering. But unlike classical cancers, CRF patients do not die over a period of time but live an uncomfortable life followed by a slow death.

Over the years (2-3 centuries), [1] mankind has engaged in searching for how best this suffering could be treated to bring succour and provide good quality of life to the sufferers. Replacement of renal function by dialysis is a major effort man has developed to achieve this. Dialysis is a means by which blood is purified of its toxic wastes, hitherto the function performed by the dying kidneys. There are two main forms of dialysis that are available to man for improving the quality and longevity of life of CRF patients. These are: (a) hemodialysis and (b) peritoneal dialysis (PD), each with its indications and contra­indications. The focus of this write up is on peritoneal membrane markers in CAPD particularly CA 125.

Peritoneal dialysis is a process by which blood is purified using the peritoneal membrane as filter. The peritoneal membrane does this job with dexterity but, at a cost because the membrane was not designed for this function but it was brought into use out of desperate efforts of man to save life. It was Rev. Stephen Hales (1743) [1] who first considered continuous peritoneal lavage in patients. Although the technique he proposed was similar to the technique later used in peritoneal dialysis, the goal of his suggestion was opposite to the aim of the dialysis treatment. The following century witnessed a lot of animal experimental works in elucidating the usefulness of perito­neal cavity as lavage and dialyzing membrane. Putnam, in 1923, was the first to describe the living peritoneum as a dialyzing membrane. [2] Ganter in the same year published his obser­vations in two uremic patients, treated with the intra-peritoneal administration of physio­logical saline. [3] Heusser and Werder using two catheters provided continuous peritoneal dialysis during experiments in dogs. They advocated similar technique in humans. [4] From 1946, many studies on peritoneal dialysis were published using either continuous or intermittent method. Thus, in 1946 and 1947 Kop [5] working under the supervision of Kolff, well known for the development of the artificial kidney, treated 21 uremic patients with 35 peritoneal dialysis sessions. For peritoneal irrigation, he used the "Kolff- solution", a solution with similar composition as used in the artificial kidney. [5] After several years of ups and downs in the fight against CRF using peritoneal dialysis, Popovich, Moncrief and co-workers presented their work titled "The definitions of a novel portable-wearable equili­brium peritoneal technique". [6] This work was a landmark second only to the introduction of the Tenckoff catheter, a silicone rubber catheter developed with two dacron cuffs for permanent peritoneal access. [5] Popovich, Moncrief and co-workers' report of 1976 gave birth to the current appellation of CAPD (Continuous Ambulatory Peritoneal Dialysis). 7 Another landmark was made at the Toronto Western Hospital when the cumbersome bottle filled fluid was changed to collapsible plastic bags that could be worn with ease by the patients. [8]

The "peritoneal membrane" used as a dialysis membrane consists of at least three layers: the mesothelium, the peritoneal capillaries and the interstitial tissue. The mesothelium is the last structure that is encountered before the peritoneal cavity. Mesothelial cells originate from the embryonic mesodermal layer just as endothelial cells. These cells are flattened epithelial cells that probably originate from subserosal multipotent cells (mesenchymal stem-cells). The mesothelium consists of a flat layer of polygonal cells forming a mosaic structure. They are covered with microvilli and are often motile. Mesothelial cells are active secretory cells as can be judged from extensive rough endoplasmic reticulum, golgi apparatus and numerous lamellar bodies. [9] The mesothelium during PD has some special features: the cells have a more cubic form and the number of cells per unit of surface area is increased.

The peritoneal cavity is the space formed by the visceral peritoneum, covering the majority of internal organs, and the parietal perito­neum, which lines the inner abdominal wall. [10] Normally, this cavity contains less than 100 ml of fluid, a surfactant-like-fluid containing phosphatidylcholine secreted by the lamellar­bodies in the mesothelial cells. [11] Anatomi­cally, various studies have suggested the surface area of peritoneum to be between 1m 2 and 2m 2 . [12],[13] However, it could be concluded that the effective surface area of the peritoneal membrane (i.e. the parts that actually participate in solute transport) is considerably less than 1m 2 . This suggests that the anato­mical surface area of the membrane is larger than the functional "effective surface area during peritoneal dialysis". [5]

   Changes in Peritoneal Membrane Top

Changes in structure and function of the peritoneal membrane are inevitable when the membrane is used for dialysis. Morphological alterations during dialysis occur in all layers of the membrane. These changes include: (a) activation of mesothelial cells and degene­ration seen in long-term patients, (b) replace­ment of the mesothelium by hyalinized collagen, (c) neo-angiogenesis mimicking that seen in diabetic retinopathy, (d) deposition of collagen IV in the extra cellular matrix, (e) stroma fibrosis probably consisting mainly of collagen I, III and IV and (f) deposition of advanced glycosylation end-products (AGE) in meso­thelium stroma and capillaries. [12],[14],[15],[16],[17],[18],[19] These changes are brought about by a number of factors. These factors include (a) bio-incom­patible nature of dialysate that exposes the peritoneal membrane to unphysiological pH due to lactate (b) the use of glucose as osmotic agent and (c) occurrence of episodes of infe­ctious peritonitis. In patients on long-term peritoneal dialysis the peritoneal cavity may become unavailable due to fibrosis, thus leading to considerable morbidity and mortality. [20],[21]

Markers of Peritoneal Membrane Status

Changes in peritoneal structure and function can be studied by peritoneal biopsy, a proce­dure that is not routinely done because of its invasive nature though it can be performed during the insertion and removal of peritoneal catheter. [14],[22],[23] In view of this, the in-vivo studies of peritoneal membrane structure have to rely on some markers that are assayed in the effluent of PD which are secreted by the various layers of the peritoneal membrane.

Interstitial and vascular structures of the peritoneal membrane can be studied by the presence of IL-6 and IL-8 in peritoneal effluent. Interstitial fibroblasts secrete IL-6 and IL-8 upon stimulation. [24],[25] Collagen formation may be reflected in effluent concen­trations of pro-collagen peptides I and III and its intra-peritoneal production has been demonstrated. [26],[27] Advanced glycosylation end-products (AGE) have been studied and their production within the peritoneal cavity has been suggested for the presence of glycated albumin and glycated IgG in peritoneal effluent. [28],[29] Pentosidine concentrations in peritoneal effluent represent part of the non­enzymatic glycosylation products derived from the interstitium. [30] The peritoneal vascu­lature can be studied using the von-Willebrand factor in the effluent; Krediet and co­workers found higher value of the von­Willebrand factor in the effluent of stable CAPD patients indicating that it is also locally released. [31],[32] The mesothelial cell is important in peritoneal dialysis because an intact mesothelial layer prevents friction between the various abdominal organs, thereby preven­ting the formation of adhesions, and the mesothelium is also involved in local host defence. In vitro, it has been shown that mesothelial cells are capable of secreting a large variety of substances. These include phosphatidylcholine, hyaluronan, coagulation and fibrinolytic factors, extensive pro and anti-inflammatory mediators, such as cytokines and chemokines and cancer antigen 125 (CA 125). [33] These substances have all been identified in peritoneal effluent. The in-vivo study of the mesothelial cell mass has become possible with finding of CA 125 in peritoneal effluent by various workers. [34],[35],[36] Serum con­centrations of CA 125 have originally been used for the identification and follow-up of patients with ovarian neoplasm, liver diseases [37],[38],[39],[40] and mesothelioma of the lung [41],[42] where increases in serum CA 125 have been shown to correlate with tumor load. [41],[42] In peritoneal dialysis without ovarian pathology or liver disease, elevated serum CA 125 concentrations have been found. This was attributed to peritoneal irritation by peritonitis or catheter implant­ation, [43] and to a limited clearance of CA 125 by the peritoneal membrane. [44] Immuno­cytochemistry studies have shown that meso­thelial cells express CA 125 and in fact, massive release of this substance was observed after lysis of these mesothelial cells. Sanusi et al have shown that peritoneal effluent CA 125 concentration is a reflection of the peri­toneal mesothelial cell mass. [36] Earlier studies have demonstrated CA 125 as a marker of mesothelial cell mass. [45],[46] Pannekeet et al and Ho-Dac-Pannekeet et al [47],[48] found low dialysate CA 125 concentrations in long term CAPD patients and a decrease of dialysate CA 125 with duration of CAPD; these findings are consistent with loss of mesothelial cell mass. Interestingly, not all mesothelial cells express CA 125. Koomen et al. [34] found that 50 to 80% cytokeratin-positive cells in omentum and peritoneal effluent stained positive with the monoclonal OC 125 antibody. With this finding, it was postulated that there are two populations of peritoneal mesothelial cells namely CA 125 positive and CA 125 negative mesothelial cells. This postulation was the subject of a study by our group [36] to chara­cterize the dialysate mesothelial cells into mesothelial cells positive for CA 125 and mesothelial cells negative for CA 125 and relative percentages of each population. Unlike previous study using cytokeratin to stain mesothelial cells, we used calretinin, a 29 kd calcium-binding protein to identify effluent mesothelial cells. Calretinin is a novel immuno­cytochemical marker for both normal meso­thelial and mesotheliomal cells and consistently stains both normal and tumor cells in cytolo­gical preparations. [49] The diagnostic sensitivity of this marker has been observed to reach 100%. [50] From this study we now know that up to 92% of peritoneal mesothelial cells express CA 125 and the ratio of positive to negative CA 125 mesothelial cells does not change with the duration of CAPD even though the mesothelial cell mass, as also CA 125 con­centration, decrease with time on CAPD. [36]

In conclusion, peritoneal dialysis has become a household means of treating ESRD world­wide and its use is not without some untoward side effects. The end result of these side effects is the development of peritoneal sclerosis, which results following multiple dialysis sessions. Serial observations of changes in the peritoneum leading to peritoneal sclerosis are very rare, and until recently our current knowledge on the development of this compli­cation was based on a compilation of findings in different patients who underwent peritoneal biopsy during the insertion or removal of peri­toneal catheter. Markers of peritoneal membrane status measured in peritoneal effluent have provided much-desired means of following each patient on peritoneal dialysis. Such marker as CA 125 is not only useful as a tool in the management of ovarian cancers, or any coelomic cancer but also has been found useful in the management of patients on CAPD. The peri­toneal mesothelial cell mass suffers degene­ration during long-term CAPD and it seems that CA 125 is a good marker to study in­ vivo peritoneal mesothelial cell mass or turn-over in CAPD patients.

   References Top

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Correspondence Address:
A A Sanusi
Renal Unit, Obafemi Awolowo University, Teaching Hospitals Complex, PMB 5538 Ile-Ife, Osun State
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