title: Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis.
abstract: Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.
authors: Division and Laboratory of Nephrology, Cliniques Universitaires Saint-Luc, Institute of Experimental and Clinical Research, Université Catholique de Louvain Medical School.
authors: Johann
authors: J
authors: Morelle
authors: Division and Laboratory of Nephrology, Cliniques Universitaires Saint-Luc, Institute of Experimental and Clinical Research, Université Catholique de Louvain Medical School.
authors: Amadou
authors: A
authors: Sow
authors: Division and Laboratory of Nephrology, Cliniques Universitaires Saint-Luc, Institute of Experimental and Clinical Research, Université Catholique de Louvain Medical School.
authors: Nicolas
authors: N
authors: Hautem
authors: Imaging Platform, Institute of Experimental and Clinical Research, and.
authors: Caroline
authors: C
authors: Bouzin
authors: School of Public Health, Université Catholique de Louvain Medical School, Brussels, Belgium; and.
authors: Ralph
authors: R
authors: Crott
authors: Division and Laboratory of Nephrology, Cliniques Universitaires Saint-Luc, Institute of Experimental and Clinical Research, Université Catholique de Louvain Medical School Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland olivier.devuyst@uzh.ch eric.goffin@uclouvain.be.
authors: Olivier
authors: O
authors: Devuyst
authors: Division and Laboratory of Nephrology, Cliniques Universitaires Saint-Luc, Institute of Experimental and Clinical Research, Université Catholique de Louvain Medical School olivier.devuyst@uzh.ch eric.goffin@uclouvain.be.
authors: Eric
authors: E
authors: Goffin
mesh_terms: D000328:Adult; D001692:Biological Transport; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009995:Osmosis; D010530:Peritoneal Dialysis / Q000009:adverse effects; D056627:Peritoneal Fibrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D014867:Water / Q000494:pharmacology*
chemical_list: D014867:Water
keywords: peritoneal dialysis; ultrafiltration; vascular endothelial growth factor; water channels
references: Q J Exp Physiol. 1987 Oct;72(4):409-37
references: 3321140
references: J Am Soc Nephrol. 2002 Feb;13(2):470-9
references: 11805177
references: Kidney Int. 1991 Aug;40(2):315-25
references: 1942781
references: J Am Soc Nephrol. 1991 Aug;2(2):122-35
references: 1954325
references: Basic Res Cardiol. 1994 Sep-Oct;89(5):397-410
references: 7535519
references: Nature. 1996 Apr 4;380(6573):435-9
references: 8602241
references: J Clin Invest. 1997 Dec 15;100(12):3131-9
references: 9399960
references: J Clin Invest. 1998 Jun 1;101(11):2567-78
references: 9616228
references: Am J Physiol. 1998 Jul;275(1 Pt 2):H234-42
references: 9688919
references: Kidney Int. 1998 Dec;54(6):2207-17
references: 9853287
references: Am J Kidney Dis. 1999 Feb;33(2):383-8
references: 10023655
references: Perit Dial Int. 2004 Nov-Dec;24(6):562-70
references: 15559486
references: Kidney Int. 2004 Dec;66(6):2437-45
references: 15569337
references: J Cell Sci. 2005 Oct 15;118(Pt 20):4731-9
references: 16188933
references: Kidney Int. 2006 Mar;69(5):927-33
references: 16518353
references: Nephrol Dial Transplant. 2006 Apr;21(4):1032-9
references: 16364990
references: Kidney Int. 2006 May;69(9):1518-25
references: 16508653
references: Perit Dial Int. 1999 Nov-Dec;19(6):517-25
references: 10641771
references: J Am Soc Nephrol. 2000 Apr;11(4):717-28
references: 10752531
references: J Clin Invest. 2000 Jul;106(1):55-62
references: 10880048
references: Perit Dial Int. 2000;20 Suppl 4:S5-21
references: 11098926
references: J Am Soc Nephrol. 2001 May;12(5):1046-51
references: 11316864
references: Kidney Int Suppl. 2003 Dec;(88):S43-9
references: 14870877
references: Perit Dial Int. 2001;21 Suppl 3:S30-4
references: 11887840
references: J Am Soc Nephrol. 2003 Dec;14(12):3205-16
references: 14638919
references: Adv Perit Dial. 2003;19:169-75
references: 14763056
references: Am J Physiol. 1984 Apr;246(4 Pt 2):R597-607
references: 6720931
references: Perit Dial Int. 2000;20 Suppl 4:S43-55
references: 11098928
references: Kidney Int Suppl. 2001 Feb;78:S42-7
references: 11168981
references: Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2604-9
references: 11226286
references: J Thromb Haemost. 2006 Jun;4(6):1186-93
references: 16706957
references: Am J Physiol Renal Physiol. 2007 Mar;292(3):F1035-43
references: 17090782
references: Adv Perit Dial. 2007;23:107-11
references: 17886614
references: Clin J Am Soc Nephrol. 2008 May;3(3):720-8
references: 18272828
references: Clin J Am Soc Nephrol. 2009 Jul;4(7):1222-9
references: 19541815
references: Kidney Int. 2010 May;77(10):904-12
references: 20375981
references: J Am Soc Nephrol. 2010 Jul;21(7):1077-85
references: 20448020
references: Kidney Int. 2010 Sep;78(6):611-8
references: 20571473
references: Nephrol Dial Transplant. 2011 Jan;26(1):291-8
references: 20566569
references: Arch Intern Med. 2011 Jan 24;171(2):110-8
references: 20876398
references: Perit Dial Int. 2011 May-Jun;31(3):269-78
references: 21454391
references: Perit Dial Int. 2011 May-Jun;31(3):245-8
references: 21555409
references: Nature. 2011 May 19;473(7347):298-307
references: 21593862
references: Nat Rev Nephrol. 2011 Sep;7(9):528-38
references: 21808281
references: Nephrol Dial Transplant. 2011 Dec;26(12):4142-5
references: 21940485
references: J Am Soc Nephrol. 2012 Mar;23(3):533-44
references: 22302194
references: Nat Med. 2012 Jul;18(7):1028-40
references: 22772564
references: J Cell Mol Med. 2012 Aug;16(8):1934-45
references: 22117756
references: PLoS One. 2012;7(11):e48647
references: 23144917
references: J Thromb Haemost. 2012 Dec;10(12):2428-37
references: 23020315
references: Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1329-38
references: 23580145
references: Kidney Int. 2014 Apr;85(4):750-8
references: 23802191
references: Am J Pathol. 1989 Apr;134(4):879-93
references: 2705508