Alpha-2-macroglobulin and albumin are useful serum proteins to detect subclinical peritonitis in the rat.
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 (alpha2M) 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, alpha2M 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 alpha2M and albumin were measured at various time points.


RESULTS
In the first study, serum alpha2M 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 alpha2M was clearly dependent on the inoculum concentration. Peak values of alpha2M were found at days 1 and 3. At all time points after inoculation, alpha2M 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 alpha2M > 40 mg/L and albumin < 32 g/L had a specificity of 100% for peritonitis.


CONCLUSIONS
Measurement of alpha2M 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 alpha2M > 40 mg/L and albumin < 32 g/L are strong indicators for peritonitis. However, normal values do not exclude infectious peritonitis.
Department of Nephrology, Academic Medical Center, University of Amsterdam, The Netherlands. roosvanw@comcast.net
Roos
R
van Westrhenen
Wytske M
WM
Westra
Jacob
J
van den Born
Raymond T
RT
Krediet
Eelco D
ED
Keuning
Johan
J
Hiralall
Cindy
C
Dragt
Liesbeth H P
LH
Hekking
D000818:Animals; D015415:Biomarkers / Q000097:blood; D015314:Dialysis Solutions / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010538:Peritonitis / Q000097:blood* / Q000209:etiology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D012720:Severity of Illness Index; D000511:alpha-Macroglobulins / Q000378:metabolism*
D015415:Biomarkers; D015314:Dialysis Solutions; D012709:Serum Albumin; D000511:alpha-Macroglobulins