Clinical utility of a rapid test for uristatin.

Objectives: Uristatin is a trypsin inhibitor present in urine that is increased in most patients with bacterial or viral infections and in many with inflammatory disorders. We included the assay of uristatin as part of a screening program carried out by pediatricians on 4207 Japanese schoolchildren to judge the ability of uristatin to identify those with an infection and (or) inflammation of any cause. We used urine dipsticks for the assay of uristatin, creatinine, albumin, blood, leukocyte esterase, and protein. We also performed quantitative assays for uristatin and creatinine. Another aim was to estimate the reference range for uristatin in schoolchildren, ages 5 to 14 yr.

Methods: We prepared dipstick pads that were impregnated with a chromogenic substrate for trypsin and measured the uristatin-caused inhibition of trypsin in urine. We measured creatinine so that the ratio of uristatin to creatinine could be calculated to correct for urine concentration.

Results: We obtained quantitative uristatin and creatinine results for 4207 children. Of these, 177 had an abnormal urine dipstick for albumin or blood or protein or leukocyte esterase or a combination of these. We used data from 3622 children to establish the reference range for the uristatin dipsticks. The 3622 were diagnosed by their pediatricians as free from an infection or inflammation of any cause and with normal urine dipstick tests. We recommend an upper reference limit for uristatin by dipstick of < or = 7.5 mg uristatin/g creatinine. The leftover 408 children ( [4207-3622-177] = 408) fell into two groups: 205 with diagnoses of no infection, possible infection, or possible inflammatory disorders. The remaining 203 children were renal disease follow-up cases. The diagnoses were based on a physical examination, microscopic urinalysis plus urine dipstick tests for albumin, blood, creatinine, protein, leukocyte esterase and a complete blood count. In the 205 children, 46 had an abnormal uristatin dipstick test, 39 had an abnormal uristatin by immunoassay, 41 had an abnormal erythrocyte sedimentation rate (ESR), 27 had an abnormal serum C-reactive protein (CRP), and one had an abnormal urine microscopic exam. For the first 938 children in the study, the agreement was 93% of negative dipstick uristatin results and immunoassays. The agreement of positive uristatin dipsticks with immunoassays was 85%. We assumed that the immunoassay results were correct. In the evaluation of 189 children with fever, 62 also had an abnormal uristatin by dipstick.

Discussion: A rapid dipstick test for uristatin read on a reflectance photometer gave values that compared well with a quantitative immunoassay method. The uristatin test is sensitive but not specific for any cause of infection or inflammation. Uristatin is easy to determine and appears to be a better indicator than fever, ESR, or CRP for the diagnosis of an infection or inflammation.