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Objective To evaluate the relationship between acquired peritoneal transport disorders and the presence of protein-losing enteropathy (PLE), and their contribution to the protein malnutrition in peritoneal dialysis (PD) patients. Patients and Methods We studied 31 clinically stable PD patients that received a fat overload diet for 3 days. We measured intestinal absorption of fecal fat (normal < 6 g/24-hour stool) and nitrogen (normal < 2 g/24-hr stool), intestinal protein permeability [fecal clearance of α1-antitrypsin (Cα1AT) (normal < 12 mL/24-hr stool)], and nutritional markers [normalized protein nitrogen appearance (nPNA), half-life medium-term proteins, and body mass index]. Peritoneal solute transport was measured by mass transfer coefficient (MTC), and water transport by peritoneal ultrafiltration (UF) capacity. To define protein maldigestion it was necessary to find high fecal nitrogen values with normal Cα1AT; PLE was defined when both values were elevated. Results High fecal nitrogen (mean 2.1 ± 1 g/24-hr stool) and fat (mean 5.8 ± 3.6 g/24-hr stool) were found in 15 patients; 6 patients had high Cα1AT levels (PLE). These 6 patients showed a worse nutritional status: lower albumin (3.57 ± 0.57 g/dL vs 3.98 ± 0.38 g/dL, p < 0.05) and transferrin (243 ± 70 mg/dL vs 272 ± 44.3 mg/dL, p < 0.05), as well as lower triglycerides (131.3 ± 31.7 mg/dL vs 187 ± 116 mg/dL, p < 0.05). Higher urea MTCs were found in 10 patients, normal in 7, and lower in 14. Higher creatinine MTCs were found in 8 patients, normal in 15, and lower in 8. Normal peritoneal UF capacity was found in 25 and lower in 6 patients. These 6 patients showed higher urea and creatinine MTCs and Cα1AT. A positive linear correlation between Cα1AT, urea MTC ( r = 0.56, p < 0.01), and creatinine MTC ( r = 0.46, p < 0.01) was found. A similar situation occurred between Cα1AT, fecal fat ( r = 0.45, p < 0.05), and fecal nitrogen ( r = 0.43, p < 0.05). Thirteen patients with previous history of peritonitis showed higher Cα1AT than those without peritonitis (10.2 ± 8 mL/24-hr stool vs 5.2 ± 4.4 mL/24-hr stool, p < 0.05). Conclusions We confirm that protein and fat malabsorption, maldigestion, and PLE are present in some PD patients. Higher fecal Cα1AT is associated with malnutrition and poorer showings of the viability markers of peritoneal membrane function.

The (NZB/NZW)F1 (B/W) mouse spontaneously develops an autoimmune disease comparable with systemic lupus erythematosus in humans. B-1 cells may be an important cell type in the development of autoimmunity and B-1 cells are distinguished from conventional B cells by developmental origin, surface marker expression and functions, including the production of autoantibodies. Here, we present findings that B-1 cells (but not conventional B cells) from the peritoneal cavity of B/W mice are resistant to 9 Gy of radiation in contrast to B-1 cells derived from C57BL/6 mice. Similar to NZB mice which have a point mutation near the mir-15a/16 loci on chromosome 14 associated with decreased expression of microRNAs miR-15a and miR-16, the B/W are hemizygous for this mutation and also have decreased miR-15a/16. We hypothesized that increased expression of targets of miR-16 in B-1 cells from the B/W mice (such as Bcl-2) could be responsible for the radioresistance observed. Transfection of peritoneal cells from B/W with miR-16 sensitizes the B-1 cells to irradiation. Moreover, 1 hour after irradiation, peritoneal cells from the radiosensitive C57BL/6 also demonstrated an increase in miR-16 expression. Our data indicate a possible role of microRNAs in contributing to the radiation response, with decreased miR-16 associated with radioresistance in B-1 cells derived from the B/W strain. The possible implications of these findings in the pathogenesis of autoimmune disease are under investigation.

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