Atorvastatin Improves Peritoneal Sclerosis Induced by Hypertonic PD Solution in Rats

Abstract

Peritoneal sclerosis is a complication of peritoneal dialysis and results in ultrafiltration failure. It is related to chronic peritoneal injury due to dialysis solution content and recurrent peritonitis. Statins have anti-inflammatory properties which may be of value in modulating responses to injury. We evaluated the capacity of atorvastatin to modify peritoneal alterations secondary to hypertonic glucose. Thirty-two non-uremic rats were divided into three groups: group I (Sham) rats received no treatment (n=11), group II received hypertonic (3.86%, 10 ml/day) PD solution (n=10) and group III received hypertonic PD solution (10 ml/day) plus 80 mg/L atorvastatin in drinking water (n=11). After four weeks, a one-hour peritoneal equilibration test (PET) was performed with 3.86% PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D 1 /D 0 glucose), ultrafiltration volume (UF), dialysate protein, TGF-beta 1 and VEGF levels were determined. Administration of atorvastatin resulted in preserved UF (4.9+/-0.8 vs 7.5+/-0.6 mL, p <0.01), protein loss (2.2+/-0.2 vs 2.1+/-0.1 g/L, p >0.05), and peritoneal thickness (53+/-3 vs 26+/-4 microm, p <0.01). D 1 /D 0 glucose was significantly reduced in the dextrose group (0.70+/-0.02 vs 0.56+/-0.04, p <0.01). Both higher levels of TGF-ss 1 (206+/-40 vs 474+/-120 pg/mL, p<0.05), and VEGF in dialysate effluent (4+/-0.4 vs 7.9+/-3 pg/mL, p>0.05), was determined in the dextrose group. Exposure to hypertonic glucose solution resulted in alterations in peritoneal transport manifested by a rapid dissipation of the glucose gradient and resultant impaired UF response. Administration of atorvastatin led to prevention of these alterations. We suggest that the anti-inflammatory properties of statins are useful in providing protection of the peritoneal membrane from the effects of hypertonic glucose.