Angiogenic Activity of the Peritoneal Mesothelium: Implications for Peritoneal Dialysis

Drawing from diverse sources including epidemiological and clinical data, surgical observations, histopathology, serosal healing responses to fibrin and fibrinolysis, tissue reaction to chronic exposure, and to exo and endotoxins, new information on mesothelial stem cells, autocrine and paracrine influences on their proliferation and collagen synthesis, and the effect of glucose on fibroconnective tissue, we have begun to piece together the pathogenetic jigsaw of fibrosis in continuous ambulatory peritoneal dialysis (CAPD). The reaction of peritoneal mesothelium and stroma to the stress of continual dialysis results in a spectrum of alterations ranging from opacification through a tanned peritoneum syndrome to sclerosing encapsulating peritonitis (SEP). Any agent that causes irritation of the mesothelial layer and induces serositis, or single severe or multiple episodes of peritonitis resulting in mesothelial loss, predisposes the peritoneum to fibroneogenesis. An accurate definition of the histopathological changes of peritoneal thickening is a prerequisite for defining pathogenesis. This paper is the first attempt to create such a framework. It is evident from many areas of study that fibrin deposition and fibrinolysis, hyalinization of the superficial stromal collagen possibly tanned through nonenzymatic glycosylation by dialysate glucose and the proliferative potential of mesothelial stem cells play an important and possibly interdependent role in excessive fibroneogenesis in certain patients on CAPD. Many of the pieces of the jigsaw are obviously still missing, and the picture is most surely incomplete. Nevertheless, the outline of the pathologic and etiologic landscape should now be discernible.

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Phosphatidylcholine Synthesis by Peritoneal Mesothelium: Its Implications for Peritoneal Dialysis

American Journal of Kidney Diseases ◽

10.1016/s0272-6386(88)80068-4 ◽

1988 ◽

Vol 12 (1) ◽

pp. 31-36 ◽

Cited By ~ 66

Author(s):

James W. Dobbie ◽

Thomas Pavlina ◽

John Lloyd ◽

Robert C. Johnson

Keyword(s):

Peritoneal Dialysis ◽

Peritoneal Mesothelium ◽

Phosphatidylcholine Synthesis

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Transport asymmetry in peritoneal dialysis: application of a serial heteroporous peritoneal membrane model

AJP Renal Physiology ◽

10.1152/ajprenal.2001.280.4.f599 ◽

2001 ◽

Vol 280 (4) ◽

pp. F599-F606 ◽

Cited By ~ 15

Author(s):

Daniele Venturoli ◽

Bengt Rippe

Keyword(s):

Molecular Weight ◽

Peritoneal Dialysis ◽

Hydraulic Conductance ◽

Small Radius ◽

Capillary Endothelium ◽

Large Radius ◽

Peritoneal Membrane ◽

Small Pore ◽

Peritoneal Mesothelium ◽

Transport Of Macromolecules

The transport of macromolecules during peritoneal dialysis is highly selective when they move from blood to dialysate but nearly completely unselective in the opposite direction. Aiming at describing this asymmetry, we modeled the peritoneal barrier as a series arrangement of two heteroporous membranes. First a three-pore membrane was considered, crossed by small [radius of the small pore ( rs) ≈ 45 Å], large [radius of the large pore ( rL) ≈ 250 Å], and transcellular pores accounting for 90, 8, and 2% to the hydraulic conductance, respectively, and with a corresponding pore area over diffusion distance ( A0/Δ x) set to 50,000 cm. We calculated the second membrane parameters by fitting simultaneously the bidirectional clearance of molecules ranging from sucrose [molecular weight = 360, permeating solute radius ( ae) ≈ 5 Å] to α2-macroglobulin (molecular weight = 820,000, ae≈ 90 Å). The results describe a second two-pore membrane with very large pores ( rL≈ 2,300 Å) accounting for 95% of the hydraulic conductance, minor populations of small ( rs≈ 67 Å) and transcellular pores (3 and 2%, respectively), and an A0/Δ x≈ 65,000 cm. The estimated peritoneal lymph flow is ≈0.3 ml/min. The two membranes can be identified as the capillary endothelium and an extracellular interstitium lumped with the peritoneal mesothelium.

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P1205ESTABLISHMENT OF HYPOCHLORITE-INDUCED PORCINE MODEL OF PERITONEAL FIBROSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1205 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Chun-Yuan Chao ◽

Chin-Ho Wu ◽

Yi-Ting Chen ◽

SHUEI-LIONG LIN ◽

Pei-Shiue Tsai

Keyword(s):

Peritoneal Dialysis ◽

Type I Collagen ◽

Porcine Model ◽

Large Animal Model ◽

Large Animal ◽

Type I ◽

Peritoneal Fibrosis ◽

Life Saving ◽

Peritoneal Mesothelium ◽

High Degree

Abstract Background and Aims Patients with kidney failure rely on life-saving peritoneal dialysis to facilitate waste exchange and maintain homeostasis of physical conditions. However, peritoneal dialysis often results in peritoneal fibrosis and organ adhesion that subsequently compromise the efficiency of peritoneal dialysis and normal functions of visceral organs. Despite rodent models provide clues on the pathogenesis of peritoneal fibrosis, no current large animal model which shares high degree of physiological and anatomical similarities to human is available, limiting their applications on the evaluation of pre-clinical therapeutic efficacy. Method In this study, we established for the first time, porcine model of peritoneal fibrosis by the use of a bleach-like chemical, sodium hypochlorite. We demonstrated that intraperitoneal injection of 30ml/kg B.W., 0.1%-0.2% (0.1mM-0.2mM) hypochlorite induced peritoneal fibrosis and visceral organ adhesions in 5-week-old piglets. Results A dose- and time-dependent severity of peritoneal fibrosis characterized by mesothelium fragmentation, αSMA+ myofibroblasts accumulation, organ surface thickening and type I collagen deposition were observed. We also demonstrated that hypochlorite-induced overexpression of IL1β, CX3CL1 and TGFβ on the peritoneal mesothelium mimicked the mechanism of peritoneal dialysis-induced peritoneal fibrosis in human patients. Conclusion This pig model could not only be used as a platform for studying fibrosis/scar formation, but can also be used to evaluate the efficacy of potential candidates on the prevention (e.g. compounds) and treatments (e.g. stem cells) for regenerative medicine.

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Semipermeability Imparted by Surface-Active Phospholipid in Peritoneal Dialysis

Peritoneal Dialysis International ◽

10.1177/089686080202200313 ◽

2002 ◽

Vol 22 (3) ◽

pp. 380-385 ◽

Cited By ~ 3

Author(s):

Yi Chen ◽

John R. Burke ◽

Brian A. Hills

Keyword(s):

Peritoneal Dialysis ◽

Osmotic Pressure ◽

Ussing Chamber ◽

Fine Powder ◽

Epithelial Surface ◽

Dipalmitoyl Phosphatidylcholine ◽

Lower Solubility ◽

Lipid Solvent ◽

Surface Active ◽

Peritoneal Mesothelium

Objective It has previously been demonstrated that a lining of surface-active phospholipid (SAPL) is reversibly bound (adsorbed) to normal peritoneal mesothelium. The lining acts as a boundary lubricant and release (anti-stick) agent preserving mechanical integrity of the epithelial surface. In a review of clinical trials on the use of SAPL (akin to “surfactant”) to restore ultrafiltration (UF) in patients on peritoneal dialysis (PD), speculation is that, by adsorption, the SAPL lining might also be imparting the semipermeability vital for UF. Design To evaluate the hypothesis, SAPL harvested from the spent dialysate of 5 patients with normal UF was deposited onto a porous, inert medium, and the resulting 7 “membranes” were clamped in an Ussing chamber used as an osmometer. Results With every “membrane,” a clinical concentration of glucose (2.5%) was able to induce a statistically significant osmotic pressure when dialyzed against saline. We also demonstrated how synthetic SAPL—in the form of dipalmitoyl phosphatidylcholine (DPPC) and an admixture of DPPC with phosphatidylglycerol (PG) called artificial lung-expanding compound (ALEC)—imparts greater osmotic pressure in proportion to an increasing glucose gradient. Our findings prove that human peritoneal SAPL has the physical capability to impart semipermeability when adsorbed to a surface. Comment As a lipid lining, adsorbed SAPL could also explain the high permeability of the natural membrane to lipophilic substances in PD. Administered as a very fine powder or as a solution in a lipid solvent, ALEC offers a potential treatment for restoring UF, if applied during the interdialytic interval. In various physical forms, ALEC and DPPC have both been widely used for two decades with complete safety in the treatment of respiratory distress syndrome in newborns. The question of formulation of exogenous SAPL in restoring UF is discussed as a complex physicochemical compromise between the higher surface activity of saturated phosphatidylcholine and its lower solubility in water.

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Scanning Electron Microscopy of Staphylococcus Epidermidis Adherence to Continuous Ambulatory Peritoneal Dialysis Catheters

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119429 ◽

1985 ◽

Vol 43 ◽

pp. 520-521

Author(s):

William J. Lamoreaux ◽

David L. Smalley ◽

Larry M. Baddour ◽

Alfred P. Kraus

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Peritoneal Dialysis ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Staphylococcus Epidermidis ◽

Sterile Saline ◽

Intravascular Devices ◽

Capd Patient ◽

Scanning Electron

Infections associated with the use of intravascular devices have been documented and have been reported to be related to duration of catheter usage. Recently, Eaton et al. reported that Staphylococcus epidermidis may attach to silastic catheters used in continuous ambulatory peritoneal dialysis (CAPD) treatment. The following study presents findings using scanning electron microscopy (SEM) of S. epidermidis adherence to silastic catheters in an in vitro model. In addition, sections of polyvinyl chloride (PVC) dialysis bags were also evaluated by SEM.The S. epidermidis strain RP62A which had been obtained in a previous outbreak of coagulase-negative staphylococcal sepsis at local hospitals was used in these experiments. The strain produced surface slime on exposure to glucose, whereas a nonadherent variant RP62A-NA, which was also used in these studies, failed to produce slime. Strains were grown overnight on blood agar plates at 37°C, harvested from the surface and resuspended in sterile saline (0.85%), centrifuged (3,000 rpm for 10 minutes) and then washed twice in 0.1 M phosphate-buffered saline at pH 7.0. Organisms were resuspended at a concentration of ca. 106 CFU/ml in: a) sterile unused dianeal at 4.25% dextrose, b) sterile unused dianeal at 1.5% dextrose, c) sterile used dialysate previously containing 4.25% dextrose taken from a CAPD patient, and d) sterile used dialysate previously containing 1.5% dextrose taken from a CAPD patient.

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