The uristatin dipstick is useful in distinguishing upper respiratory from urinary tract infections

Pugia, Michael J.; Sommer, Ronald G.; Corey, Paul F.; Anderson, Linda; Gleason, S L; Jortani, Saeed A.; Elin, Ronald J.; Gopual, Darryl L.; Valdes, Roland; Lott, John

doi:10.1016/j.cccn.2003.10.019

Cited by 11 publications

(22 citation statements)

References 16 publications

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“…The Ͼ50-kDa bands we detected here most likely correspond to heavy chain components, P␣I or ITI. The 21-kDa BK we found corresponds to either the ϳ25-kDa BK form identified by Suzuki et al (43) as deglycosylated BK or a 20-kDa fragment of BK, also known variously as urinary trypsin inhibitor 2 (UTI-2) (15,22) or uristatin (37). LMM bands (Ͻ20 kDa) are products of proteolytic degradation.…”

Section: Discussionmentioning

confidence: 57%

Urine protein markers distinguish stone-forming from non-stone-forming relatives of calcium stone formers

Bergsland

Kelly²,

Coe³

et al. 2006

American Journal of Physiology-Renal Physiology

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We have investigated urine protein inhibitors of calcium oxalate crystallization to determine whether variations in these proteins are associated with kidney stone disease and whether protein measurements improve the identification of stone formers compared with conventional risk factors (RF). Using Western blotting, we studied variations in the electrophoretic mobility patterns and relative abundances of crystallization-inhibitory proteins in urine from 50 stone-forming (SF) and 50 non-stone-forming (NS) first-degree relatives of calcium SF patients, matched by gender and age. Standard urine chemistry stone risk measurements were also made. Multivariate discriminant analysis was used to test the association of these proteins with nephrolithiasis. Differences in form and abundance of several urine proteins including inter-␣-trypsin inhibitor (ITI), prothrombin fragment 1 (PF1), CD59, and calgranulin B (calB) were found to be associated with stone formation. By multivariate discriminant analysis, measurements of forms of PF1, ITI, and calB in men and ITI and CD59 in women, classified 84% of men and 76% of women correctly by stone status. In contrast, standard urine chemistry RF identified only 70% of men correctly and failed to distinguish female SF from NS. Thus a small subset of protein measurements distinguished SF from NS far better than conventional RF in a population of relatives of calcium SF,

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Section: Discussionmentioning

confidence: 57%

Urine protein markers distinguish stone-forming from non-stone-forming relatives of calcium stone formers

Bergsland

Kelly²,

Coe³

et al. 2006

American Journal of Physiology-Renal Physiology

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“…The prevalent uTi forms include Bikunin (molecular weight=E30 kDa) and its Uristatin fragments, which lack the chondroitin sulfate chain. These fragments are generally o17 KDa, and all exhibit trypsin inhibitory activity (7,8).…”

Section: Introductionmentioning

confidence: 99%

Sensitive noninvasive marker for the diagnosis of probable bacterial or viral infection

Jortani

Pugia

Elin

et al. 2004

Clinical Laboratory Analysis

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Urinary trypsin inhibitor (uTi) is a product of elastase-mediated degradation of interleukin-alpha-inhibitor (I-alpha-I). Its activity increases in the urine of patients with a malignancy, inflammation, or infection, or in late pregnancy. The objective of this study was to compare the sensitivity of uTi in urine with that of serum quantitative C-reactive protein (CRP) for diagnosing infection, as indicated by white cell response and clinical assessment. Ninety controls and 171 patients with various systemic infections were enrolled. We measured uTi enzymatically on a Cobas Fara (Roche Diagnostics). Patients were separated into bacterial, probable bacterial, viral, or probable viral groups based on the results of a complete blood count with differential (CBC), urinalysis (UA), and clinical assessment. In the bacterial (n=70) and control (n=90) groups, the uTi values (mean+/-SE) were 25.3+/-3.1 mg/L and 2.8+/-0.8 mg/L, respectively. uTi (at 2.7 mg/L) had a diagnostic sensitivity of 91% and specificity of 82% (AUC=0.889), whereas CRP (at a cutoff of 10 mg/L) had a sensitivity and specificity of 82% and 96%, respectively (AUC=0.921). As a marker of infection (positive in both bacterial and viral groups), uTi had a sensitivity of 91% (AUC=0.884) vs. 89% (AUC=0.828) for CRP. Our data indicate that uTi has sufficient clinical sensitivity for screening systemic infections, and may have diagnostic value as a noninvasive test.

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“…All active urinary trypsin inhibitors in a urine specimen can be measured by inhibition of trypsin [4][5][6]. The diagnostic use of this measurement as a nonspecific test for infection or inflammation is similar to the finding with C-reactive protein (CRP), a complete blood count (CBC) or sedimentation rate [4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…Further, they inhibited the members of the trypsin family of serine proteases. Variations owing to fragmentation of uTi and the presence in the N-linked glycoconjugate were demonstrated by Western blot analysis with an uTi polyclonal antibody (Pab) [6].…”

Section: Introductionmentioning

confidence: 99%

“…Bikunin is also part of the precursor protein pre-alpha-1-microglobulin/bikunin (AMBK). New forms of urinary trypsin inhibitors (e.g., uristatin) were discovered recently in patients with an acute phase reaction [4][5][6]. Uristatins contain either of the Kunitz inhibitor domains; however, they always lack the O-linked glycoconjugate chain.…”

Section: Introductionmentioning

confidence: 99%

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Immunological evaluation of urinary trypsin inhibitors in blood and urine: Role of N- & O-linked glycoproteins

et al. 2006

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Urinary trypsin inhibitors (uTi) suppress serine proteases during inflammation. After liberation from proinhibitors (P-alpha-I and I-alpha-I) by the white blood cell (WBC) response, uTi readily pass through the kidneys into urine. A key uTi, bikunin, is attached to O-linked and N-linked glycoconjugates. Recently, uTi inhibitors, called uristatins, were found to lack the O-linked glycoconjugates. Monoclonal antibodies were produced using purified uristatin and screened for binding differences to uristatin, bikunin, P-alpha-I, and I-alpha-I. Antibody-binding patterns were characterized using immunoaffinity binding onto protein-chip surfaces and analysis by Surface Enhanced Laser Desorption/Ionization mass spectrometry (SELDI), using specimens from patients and from purified uTi standards. Antibodies were developed and used in an enzyme-linked immunosorbent assay (ELISA) method for uTi measurement in urine and plasma specimens. ELISA was performed on specimens from normal, presumed healthy, controls and from patients who had been screened for inflammation using a high sensitivity C-reactive protein (CRP) test and a complete blood count (CBC). Polyclonal antibody against uTi showed cross-reactivity with the Tamm-Horsfall protein (THP) and with proinhibitors. Screening of anti-uTi monoclonal antibodies (Mab) revealed antibodies that did not cross-react with either of the above, thus providing a tool to measure both uristatin and bikunin in urine with Mab 3G5 and in plasma with Mab 5D11. The monoclonal antibody 5D11 cross-reacts with specific N-linked glycoconjugates of uristatin present in plasma. In ca 96% of healthy adults, uTi were present at <12 mg/l in urine and <4 mg/l in plasma. We also found that patients with an inflammation and a CRP of >2.0 mg/l had higher urinary concentrations of uTi than the control population in every subject. Free uristatin and bikunin pass readily into urine and are primarily bound to heavy chains that constitute the proinhibitor form in plasma.

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The uristatin dipstick is useful in distinguishing upper respiratory from urinary tract infections

Cited by 11 publications

References 16 publications

Urine protein markers distinguish stone-forming from non-stone-forming relatives of calcium stone formers

Urine protein markers distinguish stone-forming from non-stone-forming relatives of calcium stone formers

Sensitive noninvasive marker for the diagnosis of probable bacterial or viral infection

Immunological evaluation of urinary trypsin inhibitors in blood and urine: Role of N- & O-linked glycoproteins

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