Influence of renin-angiotensin-aldosterone system-blocking drugs on peritoneal membrane in peritoneal dialysis patients.
Therapy with renin-angiotensin-aldosterone system (RAAS)-blocking drugs prevents the development of fibrosis and angiogenesis in animal models and humans. In our study we have evaluated the systemic effect of RAAS blockade and the effect on peritoneal growth factors, cytokine production and membrane transport characteristics in patients on peritoneal dialysis. Thirty-seven peritoneal dialysis (PD) patients were enrolled in our cross-sectional study. Aldosterone and angiotensin II concentrations were measured in serum to determine the RAAS activity. The inflammatory and profibrotic activity was evaluated by measuring the concentration of C-reactive protein (CRP), serum albumin, and peritoneal concentration of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β (TGF-β) and cancer antigen-125 (CA-125). The transport characteristics of the peritoneal membrane were analyzed with a peritoneal equilibration test (PET). Results were compared between the group with RAAS-blocking drugs (RAAS group) and the group without them (non-RAAS group). Mean serum aldosterone concentration was significantly lower in patients treated with ARB-blocking drugs (P = 0.001) and serum angiotensin II concentration was lower in patients treated with ACE inhibitors (P = 0.009). RAAS blockade resulted in lower peritoneal PAI-1 levels (748.1 to 1222.7 ng/L; P = 0.07) without any influence on CRP, peritoneal concentrations of IL-6, VEGF, TGF-β and CA-125, or alteration in peritoneal membrane characteristics tested by PET. RAAS-blocking drugs could be effective in preventing peritoneal fibrosis due to possible reduction of peritoneal PAI-1 concentrations that have already been etiologically linked with fibrin deposition in the pathogenesis of encapsulating peritoneal sclerosis.
Department of Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Alijana
A
Trošt Rupnik
Jernej
J
Pajek
Andrej
A
Guček
Joško
J
Osredkar
Damjan
D
Kovač
Andrej
A
Bren
Dimitrij
D
Klančič
Silvan
S
Saksida
Igor
I
Rus
Mateja
M
Globokar
Andrej
A
Drozg
Marjeta
M
Lešnik
Zala
Z
Plešivčnik
Robert
R
Ekart
Simona
S
Lopert
Jelka
J
Lindič
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000805:Angiotensin III / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001692:Biological Transport; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D056627:Peritoneal Fibrosis / Q000209:etiology / Q000517:prevention & control; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D017395:Plasminogen Activator Inhibitor 1; D000805:Angiotensin III; D000450:Aldosterone
Encapsulating peritoneal sclerosis; Peritoneal dialysis; Peritoneal transport; Plasminogen activator inhibitor-1; Renin-angiotensin-aldosterone system blocking drugs; Renin-angiotensinaldosterone system