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      The impact of lipocalin-type-prostaglandin-D-synthase as a predictor of kidney disease in patients with type 2 diabetes

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          Abstract

          Hypertension and diabetes are clinical conditions which contribute to the development of chronic kidney disease as well as risk factors for cardiovascular events. In recent years, lipocalin-type-prostaglandin-D-synthase (beta trace protein; BTP) has increasingly been studied as an alternative to creatinine for the evaluation of renal function as well as for being a possible biomarker for cardiovascular disease. It is expected that the levels of BTP in patients with cardiovascular disease are elevated, as is the case with patients with renal dysfunction. The objective of this study is to realize a systematic review of the pertinent literature in respect to BTP as a biomarker of renal dysfunction in diabetic patients. Using the database MEDLINE, a search up to year 2014 was conducted using the follow descriptors: “lipocalin type prostaglandin d synthase” AND “diabetes”; “lipocalin type prostaglandin d synthase” and “diabetic nephropathy”; “beta trace protein” AND “diabetes”; “beta trace protein” AND “diabetic nephropathy”. The criteria used for inclusion were the presence of the referring to terms in title or abstract and study conducted in humans. About 17 articles were selected, of which six articles were duplicates, and of which six articles did not investigate any possible relationship between the protein (BTP) and either diabetes or nephropathy. The final result yielded five articles to be analyzed. This review found BTP is not influenced by race, by body mass index nor by patient’s sex. BTP can be considered as a reliable early biomarker of renal dysfunction in diabetics. BTP is associated with metabolic syndrome and is also associated with greater cardiovascular risk. Prospective data establishing a correlation between BTP and mortality would have been of great interest, but such articles were not found in this review.

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          Most cited references 12

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          β-Trace protein: a marker of GFR and other biological pathways.

          β-Trace protein (BTP), also known as lipocalin prostaglandin D2 synthase (L-PGDS; encoded by the PTGDS gene), is a low-molecular-weight glycoprotein and an emerging novel marker of glomerular filtration rate. BTP is an important constituent of cerebral spinal fluid and is found in much lower concentrations in blood. Its serum origin and renal handling remain poorly understood. Unlike serum creatinine, BTP is not physiologically inert. It possesses both ligand-binding and enzymatic properties. BTP catalyzes the conversion of prostaglandin H2 (PGH2) to PGD2. PGD2 is an eicosanoid involved in a variety of important physiologic processes, including platelet aggregation, vasodilation, inflammation, adipogenesis, and bone remodeling. Several studies now have documented BTP's strong association with glomerular filtration rate, end-stage renal disease, cardiovascular disease, and death in a variety of different patient populations. This review provides an overview of the biochemistry, physiology and metabolism, biological functions, and measurement of BTP; summarizes the evidence for BTP as a marker of both kidney function and cardiovascular disease; and then considers the interplay between its biological properties, serum concentration, and patient outcomes.
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            Comparison of serum concentrations of β-trace protein, β2-microglobulin, cystatin C, and creatinine in the US population.

            β-trace protein (βTP), β2-microglobulin (β2M), and cystatin C (CysC) have advantages over creatinine for estimating GFR and prognosis. This study compares the distribution of all four markers in the general population and their associations with possible determinants of GFR. βTP and β2M were measured in 7596 participants (aged ≥12 years) of the Third National Health and Nutrition Examination Survey (1988-1994). βTP and β2M concentrations and the proportion of persons with elevated (≥99th percentile for young healthy participants) βTP (≥0.81 mg/L), β2M (≥2.80 mg/L), standardized CysC (≥1.03 mg/L), and creatinine (≥1.2 mg/dl for men and ≥1.0 mg/dl for women) were compared across demographic and clinical factors. Elevated βTP, β2M, and CysC showed stronger associations with age than elevated serum creatinine, the prevalence of elevated levels reaching 47%, 44%, 58%, and 26%, respectively, by age 80 years. βTP, CysC, and creatinine were higher in men but β2M was not associated with sex. Mexican Americans had lower βTP, β2M, CysC, and creatinine compared with non-Hispanic whites. Hypertension and higher C-reactive protein were associated with elevations in all markers, whereas non-Hispanic black race, body mass index, diabetes, smoking status, triglycerides, HDL cholesterol, and education were not associated in a consistent manner across the different markers. βTP, β2M, CysC, and creatinine differ in their associations with demographic and clinical factors, suggesting variation in their non-GFR determinants. Future studies should examine these markers with measured GFR to determine their diagnostic and prognostic utility.
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              β-Trace protein: from GFR marker to cardiovascular risk predictor.

              β-Trace protein, also known as Lipocalin type prostaglandin D synthase, is a low-molecular mass glycoprotein (between 23,000 and 29,000 Da depending on the degree of glycosylation) that converts prostaglandin H2 into prostaglandin D2. β-Trace protein was initially isolated from cerebrospinal fluid and served as a marker of cerebrospinal fluid leakage; however, its cDNA and gene have been isolated in numerous human body tissues, including central nervous system, retina, melanocytes, heart, and male genital organs. In recent years, β-trace protein has emerged as a promising novel endogenous marker of GFR, representing a more sensitive marker for mild kidney dysfunction than serum creatinine. In this regard, β-trace protein has been proposed as an alternative marker to Cystatin C for measuring kidney function. Beyond its role for estimating renal function, β-trace protein is also emerging as a novel biomarker in cardiovascular risk. It has been associated with several cardiovascular disorders, playing a potential role for prognostic stratification in patients with acutely decompensated heart failure and acute coronary syndromes and being advocated as a novel marker for cardiovascular risk prediction.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                22 June 2015
                : 9
                : 3179-3182
                Affiliations
                [1 ]General Practice Department, Federal University of São Paulo, São Paulo, Brazil
                [2 ]Clinical Analysis Laboratory, ABC Medical School, Federal University of São Paulo, São Paulo, Brazil
                [3 ]Biological Sciences Department, Federal University of São Paulo, São Paulo, Brazil
                Author notes
                Correspondence: Marcelo Rodrigues Bacci, General Practice Department, ABC Medical School, Av Principe de Gales, 821, Santo Andre, São Paulo 09060-650, Brazil, Tel +55 11 981937005, Email mrbacci@ 123456yahoo.com
                Article
                dddt-9-3179
                10.2147/DDDT.S82100
                4482380
                26124640
                © 2015 Bacci et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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