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Basic |
Department of Nephrology,1 Academic Medical Center, University of Amsterdam; Department of Molecular Cell Biology and Immunology,2 VU University Medical Center, Amsterdam; Department of Clinical Chemistry,3 Academic Medical Center, University of Amsterdam, The Netherlands
Correspondence to: R. van Westrhenen, Department of Nephrology, F4-215, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.roosvanw{at}comcast.net
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 (
2M) 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, 2M 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
2M and albumin were measured at various time points. Results: In the first study, serum 2M 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 2M was clearly dependent on the inoculum concentration.
Peak values of 2M were found at days 1 and 3. At all time points after
inoculation, 2M 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 2M >40 mg/L and albumin <32 g/L had a
specificity of 100% for peritonitis. Conclusions: Measurement of 2M 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 2M >40 mg/L
and albumin <32 g/L are strong indicators for peritonitis. However, normal
values do not exclude infectious peritonitis.
KEY WORDS: Albumin; alpha-2-macroglobulin; peritonitis; rat model; chronic peritoneal exposure.
Received 3 October 2004; accepted 8 June 2005.
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