This study examined the morphologic features of the parietal peritoneal membranes of 130 patients undergoing peritoneal dialysis (PD) and compared them with the features of the peritoneal membranes of normal individuals, uremic predialysis patients, and patients undergoing hemodialysis. The median thickness of the submesothelial compact collagenous zone was 50 µm for normal subjects, 140 µm for uremic patients, 150 µm for patients undergoing hemodialysis, and 270 µm for patients undergoing PD (P 97 mo, 700 µm (n = 19)]. Vascular changes included progressive subendothelial hyalinization, with luminal narrowing or obliteration. These changes were absent in samples from normal subjects but were present in 28% of samples from uremic patients and 56% of biopsies from patients undergoing PD. In the PD group, the prevalence of vasculopathy increased significantly with therapy duration (P = 0.0001). The density of blood vessels per unit length of peritoneum was significantly higher for patients with membrane failure and was correlated with the degree of fibrosis (P = 0.01). For the first time, a comprehensive cross-sectional analysis of the morphologic changes in the peritoneal membranes of patients undergoing PD is provided. The infrequency of fibrosis in the absence of vasculopathy suggests that vasculopathy may predispose patients to the development of fibrosis. This study provides a sufficiently large cohort of samples to allow structure-function relationships to be established, as well as providing a repository of tissue for further studies.

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Morphologic Changes in the Peritoneal Membrane of Patients with Renal Disease

https://www.ajkd.org/article/S0272-6386(12)80506-3/pdf

New Concepts in Molecular Biology and Ultrastructural Pathology of the Peritoneum: Their Significance for Peritoneal Dialysis

Patients treated with continuous ambulatory peritoneal dialysis (CAPD) may suffer from recurrent peritonitis episodes caused by Staphylococcus epidermidis. Early recruitment of granulocytes from the peripheral blood is important for the peritoneal antibacterial defense of CAPD patients. In this study, human peritoneal mesothelial cells were shown to produce high levels of interleukin-8 (IL-8) in response to IL-1 beta and tumor necrosis factor-alpha (TNF alpha) but not lipopolysaccharide or S. epidermidis. Coculture of peritoneal macrophages with S. epidermidis induced high levels of IL-1 alpha, IL-1 beta, and TNF alpha in 24-h-conditioned medium. Preincubation of this medium with anti-TNF alpha, anti-IL-1 alpha, or anti-IL-1 beta partially blocked stimulation of IL-8 production by mesothelial cells. Added together, these antibodies abolished IL-8 production to a level just above background. Migration of granulocytes to the stimulated mesothelial cell-conditioned medium could be totally blocked with rabbit polyclonal anti-IL-8 antibody. Thus, mesothelial cells are important for the recruitment of granulocytes into the peritoneal cavity.

Interleukin-8 production by human peritoneal mesothelial cells in response to tumor necrosis factor-alpha, interleukin-1, and medium conditioned by macrophages cocultured with Staphylococcus epidermidis.

Replication of the basement membrane of the peritoneal capillaries and the mesothelium is observed in all uremic patients after a period of continuous ambulatory peritoneal dialysis (CAPD). Biopsy specimens of the parietal peritoneum were taken in diabetic and non-diabetic patients on insertion or repositioning of the CAPD catheter. The basement membrane of the capillaries and mesothelium was normal in non-diabetics on insertion of the catheter, but after 2 to 66 months of CAPD, multiple replication was found. In nearly all the diabetics there was already replication of the basement membrane of the peritoneal capillaries before CAPD was begun but the basement membrane of the mesothelium was intact. After several months of CAPD thickening of the basement membrane of the capillaries was found in 36% of diabetics, sometimes to the point of occlusion. After CAPD, replication of the basement membrane of the mesothelium has been observed in both diabetics and non-diabetics although it is initially perfectly normal in both. CAPD is proposed as an experimental model for diabetic microangiopathy in man.

Peritoneal vascular changes in continuous ambulatory peritoneal dialysis (CAPD): an in vivo model for the study of diabetic microangiopathy.

The source and possible significance of hyaluronan in the peritoneal cavity

The structure of the peritoneum has been studied by scanning and transmission electron microscopy and by light microscopy in 38 biopsies of 22 patients undergoing CAPD. Before CAPD the mesothelium was characterized by flattened cells with protruding nuclei, numerous microvilli and many pinocytotic vesicles. After prolonged CAPD there is a reduction and subsequent disappearance of microvilli and a vacuolar separation of cells from the basement membrane, accompanied by widening of intercellular junctions. Neither ultrafiltration rate nor small solute clearance change with these structural alterations. During peritonitis there is extensive cellular necrosis with denuding of the basement membrane. After recovery the mesothelium is replaced by thick fibrous connective tissue.

The Morphology of the Peritoneum in CAPD Patients

In 1982 Hills(1) demonstrated by thin-layer chromatography (TLC) that the fluid which naturally wets mesothelial membranes is a phospholipid consisting of 92% phosphatidylcholine. He called this phospholipid surface-active material (SAM). In 1985 Grahame(2) suggested that SAM may play a role in the physiology of peritoneal dialysis. Surface-active material normally adheres to the visceral and parietal walls of the peritoneum and is kept in situ by the attraction between positively charged choline and the negatively charged mesothelium. We know that SAM is a strong surfactant; it causes the peritoneum to become water repellent and brings about mechanical lubrication of endoperitoneal organs. The layer of liquid stagnating on the peritoneal surface creates resistance(3) to peritoneal transport and, consequently, the degree of resistance will vary according to the thickness of this layer.

N. DiPaolo

Papers

The Morphology of the Peritoneum in CAPD Patients

Phosphatidylcholine A Physiological Modulator of the Peritoneal Membrane