Atorvastatin Improves Peritoneal Sclerosis Induced by Hypertonic PD Solution in Rats

Abstract

Background 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. Methods 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 (D1/D0 glucose), ultrafiltration volume (UF), dialysate protein, TGF-ß1 and VEGF levels were determined. Results 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 μm, p <0.01). D1/D0 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-ß1 (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. Conclusion 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.