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      Urinary β-trace protein : A unique biomarker to screen early glomerular filtration rate impairment

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          Abstract

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          Abstract

          The screening for chronic kidney disease (CKD) patients needs the measurement of serum markers like creatinine. Our previous results indicated that urinary excretion of β-trace protein (BTP), a low-molecular-weight protein (23–29 kDa), is increased in CKD patients from stage 2. The aim of this study was to assess the major determinants of urinary excretion of BTP and to evaluate its feasibility as noninvasive marker of glomerular filtration rate (GFR) impairment.

          We studied 355 CKD patients (198 males), aged 15 to 83 years, in stable clinical conditions, classified in the different stages of CKD on the basis of GFR (renal clearance of 99mTc-diethylenetriamine penta-acetic acid). At the same time, we measured serum and urinary creatinine and BTP, and urinary albumin. Urinary excretion of BTP and albumin was expressed as mg/g urinary creatinine. Fractional clearance of BTP was calculated as the ratio of BTP clearance to creatinine clearance (%).

          Urinary excretion of BTP is mainly determined by its serum concentration and by the level of GFR, and to a lower extent by urinary albumin excretion. In fact, urinary BTP (U-BTP) and fractional clearance of BTP progressively and significantly increased along with the reduction of GFR and the concurrent rise in serum BTP (S-BTP). The relationship of U-BTP with GFR was very similar to that of S-BTP with GFR: U-BTP mirrors S-BTP. The accuracy of U-BTP to screen patients with GFR <90 mL/min/1.73 m 2 was good (area under the curve 0.833), its sensitivity was 76.9%, specificity 80%, and positive predictive value 84.9%. Sensitivity of U-BTP was quite similar to that of S-BTP and serum creatinine.

          The major determinants of urinary excretion of BTP are S-BTP and GFR. U-BTP may be a suitable noninvasive marker to screen the general population for detection of GFR <90 mL/min/1.73 m 2.

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          Biomarkers of renal function, which and when?

          Acute kidney injury (AKI) and chronic kidney disease (CKD) are conditions that substantially increase morbidity and mortality. Although novel biomarkers are being used in practice, the diagnosis of AKI and CKD is still made with surrogate markers of GFR, such as serum creatinine (SCr), urine output and creatinine based estimating equations. SCr is limited as a marker of kidney dysfunction in both settings and may be inaccurate in several situations, such as in patients with low muscle mass or with fluid overload. New biomarkers have the potential to identify earlier patients with AKI and CKD and in the future potentially intervene to modify outcomes.
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            Renal filtration, transport, and metabolism of low-molecular-weight proteins: a review.

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              Renal dysfunction induced by cadmium: biomarkers of critical effects.

              Cadmium (Cd) is cumulative poison which can damage the kidneys after prolonged exposure in the industry or the environment. Renal damage induced by Cd affects primarily the cellular and functional integrity of the proximal tubules, the main site of the renal accumulation of the metal. This results in a variety of urinary abnormalities including an increased excretion of calcium, amino acids, enzymes and proteins. These effects have been documented by a large number of studies conducted during more than two decades in experimental animals and in populations environmentally or occupationally exposed to Cd. There is now a general agreement to say that the most sensitive and specific indicator of Cd-induced renal dysfunction is a decreased tubular reabsorption of low molecular weight proteins, leading to the so-called tubular proteinuria. beta2-microblobulin, retinol-binding protein and alpha1-microglobulin are the microproteins the most commonly used for screening renal damage in populations at risk. Tubular dysfunction develops in a dose-dependent manner according to the internal dose of Cd as assessed on the basis of Cd levels in kidney, urine or in blood. Depending on the sensitivity of the renal biomarker and the susceptibility of the exposed populations, the thresholds of urinary Cd vary from 2 to 10 microg/g creatinine. The thresholds associated with the development of the microproteinuria, the critical effect predictive of a decline of the renal function, is estimated around 10 microg/g creatinine for both occupationally and environmentally exposed populations. Much lower thresholds have been reported in some European studies conducted on the general population. These low thresholds, however, have been derived from associations whose causality remains uncertain and for urinary protein increases that might be reversible. Cd-induced microproteinuria is usually considered as irreversible except at the incipient stage of the intoxication where a partial or complete reversibility has been found in some studies.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                December 2016
                09 December 2016
                : 95
                : 49
                : e5553
                Affiliations
                Department of Clinical and Experimental Medicine, Division of Nephrology, University of Pisa, Italy.
                Author notes
                []Correspondence: Carlo Donadio, Department of Clinical and Experimental Medicine, University of Pisa, 56123 Via Savi 10, Pisa, Italy (e-mail: carlo.donadio@ 123456med.unipi.it ).
                Article
                MD-D-16-02550 05553
                10.1097/MD.0000000000005553
                5266030
                27930558
                c1410e41-f38c-4894-92d7-bb586d5ce92c
                Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0

                History
                : 12 April 2016
                : 9 November 2016
                : 13 November 2016
                Categories
                5200
                Research Article
                Diagnostic Accuracy Study
                Custom metadata
                TRUE

                β-trace protein,chronic kidney disease,glomerular filtration rate,low-molecular-weight proteins,noninvasive screening,sensitivity,specificity

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