Alpha-2-Macroglobulin and Albumin are Useful Serum Proteins to Detect Subclinical Peritonitis in the Rat

Abstract

Background

In experimental peritoneal dialysis (PD) studies, the occurrence of peritonitis is a confounder in the interpretation of effects of chronic peritoneal exposure to dialysis solutions. Since fluid cannot be drained in most experimental PD models in the rat, it is impossible to diagnose peritonitis based on dialysate white blood cell counts. To study the value of serum markers for the presence of peritonitis, alpha-2-macroglobulin (α2M) and albumin were measured in rats with and without peritonitis after chronic exposure to dialysis solutions. To further investigate the time course of these markers in relation to the severity of peritonitis, nondialyzed rats were challenged with increasing numbers of bacteria and followed for 28 days.

Methods

In the first study, α2M and albumin were measured in rats exposed to glucose/lactate-based dialysis fluid before sacrifice. A comparison was made between animals with peritonitis, as judged from the presence of extensive infiltrates after sacrifice (gold standard) and/or clinical signs of peritonitis, or absence of peritonitis and infiltrates. In the second study, rats were intraperitoneally (IP) injected with 3 different concentrations of Staphylococcus aureus, and serum α2M and albumin were measured at various time points.

Results

In the first study, serum α2M was higher and serum albumin was lower in animals with peritonitis compared to animals without peritonitis (both p < 0.05). In the second study, induction of α2M was clearly dependent on the inoculum concentration. Peak values of α2M were found at days 1 and 3. At all time points after inoculation, α2M was higher in all injected groups compared to the control group. Serum albumin values decreased in the highest inoculum group and remained decreased until 28 days after IP injection. Despite a low sensitivity, serum α2M >40 mg/L and albumin <32 g/L had a specificity of 100% for peritonitis.

Conclusions

Measurement of α2M and albumin once per month is an additional tool in the diagnosis of silent peritonitis in the chronic peritoneal exposure model in the rat. Levels of α2M >40 mg/L and albumin <32 g/L are strong indicators for peritonitis. However, normal values do not exclude infectious peritonitis.