Blockage of the renin-angiotensin system in peritoneal dialysis.

Correspondence to: Hugo Abensur. University Hospital, School of Medicine of the University of São Paulo. AV. Macuco, no 58, apto 11. São Paulo, SP, Brazil. CEP: 04523-000. E-mail: [email protected] Blockade of the renin-angiotensin system (RAS) in patients on peritoneal dialysis offers three potential benefits: reduced cardiovascular mortality, preservation of residual renal function, and maintenance of peritoneal membrane integrity. No studies have examined the specific effects of RAS blockade on the mortality of patients on peritoneal dialysis. But evidence suggests patients with chronic kidney disease on hemodialysis may benefit from RAS blockade.1,2 However, Wong et al.3 reported a correlation between angiotensin converting enzyme activity, macroangiopathy, and death in 49 diabetic patients on peritoneal dialysis. Residual renal function preservation is a determining factor in the survival of patients undergoing peritoneal dialysis.4 RAS blockade is an important therapeutic tool to prevent the progression of chronic kidney disease.4-6 A large observational study enrolling over 1000 patients on peritoneal dialysis showed that patients on angiotensin converting enzyme inhibitors had delayed development of anuria.7 Li et al.8 reported that ramipril protected residual renal function of patients on peritoneal dialysis. The 2006 American guidelines for peritoneal dialysis recommend the use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers to preserve residual renal function in patients on peritoneal dialysis.9 However, some authors have failed to demonstrate the benefits of RAS blockade in preserving residual renal function of patients on peritoneal dialysis.10,11 Over the course of peritoneal dialysis the peritoneal membrane thickens, loses its mesothelial layer, undergoes neoangiogenesis, and develops fibrosis. These changes are caused by uremia, insults resulting from episodes of peritonitis, lack of bio-compatibility with the dialysis solution, and presence of a peritoneal dialysis catheter. The high concentration of glucose in the dialysis solution has been identified as the main causal agent of damages to the peritoneal membrane. These insults stimulate the production of inflammatory cytokines such as interleukin-6, transforming growth factor-β (TGF-β), and vascular endothelium growth factor (VEGF), among others.12 Mesothelial cells are believed to turn into mesenchymal cells, which then infiltrate the submesothelial layer and produce various cytokines that promote vascular proliferation and fibrosis.13 These histopathological changes have been correlated with fast transport patterns characterized by rapid absorption of glucose from the dialysate intraperitoneally, early dissipation of the osmotic gradient, and reduced ultrafiltration. The final pathway of this inflammatory process is sclerosing peritonitis, which in its most severe form has been associated with intestinal obstruction in what is called sclerosing encapsulating peritonitis.14 Various measures have been studied in the areas of prophylactic care and treatment of peritoneal injuries, such as the use of more biocompatible dialysis solutions, antioxidants such as N-acetylcysteine,15 antifibrotic agents such as tamoxifen,16 immunosuppressants,16 corticosteroids, and others. RAS activation has been correlated with fibrosis, mainly due to