Urine Retinol-Binding Protein 4: A Functional Biomarker of the Proximal Renal Tubule

被引:65
作者
Norden, Anthony G. W. [1 ]
Lapsley, Marta [2 ]
Unwin, Robert J. [3 ]
机构
[1] Cambridge Univ Teaching Hosp NHS Trust, Addenbrookes Hosp, Dept Clin Biochem, Cambridge, England
[2] St Helier Hosp, South West Thames Inst Renal Res, Sutton, Surrey, England
[3] Royal Free Campus & Hosp, UCL Med Sch, UCL Ctr Nephrol, London, England
来源
ADVANCES IN CLINICAL CHEMISTRY, VOL 63 | 2014年 / 63卷
关键词
MOLECULAR-WEIGHT PROTEINS; ACUTE KIDNEY INJURY; GELATINASE-ASSOCIATED LIPOCALIN; MASS-SPECTROMETRIC IMMUNOASSAY; IDIOPATHIC FANCONI-SYNDROME; LINKED-IMMUNOSORBENT-ASSAY; HIV-INFECTED PATIENTS; BASENJI DOGS; HUMAN PLASMA; INTERSTITIAL NEPHRITIS;
D O I
10.1016/B978-0-12-800094-6.00003-0
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Measurement of retinol-binding protein 4 in urine (uRBP4) is arguably the most sensitive biomarker for loss of function of the human proximal renal tubule. Megalin- and cubilin-receptor-mediated endocytosis normally absorbs >99% of the approximately 1.5 g/24 h of protein filtered by the renal glomerulus. When this fails there is "tubular proteinuria," comprising uRBP4, albumin, and many other proteins and peptides. This tubular proteinuria is a consistent feature of the renal Fanconi syndrome (FS) and measurement of uRBP4 appears to be an excellent screening test for FS. FS occurs in rare inherited renal diseases including cystinosis, Dent disease, Lowe syndrome, and autosomal dominant FS. Acquired FS occurs in paraproteinemias, tubulointerstitial renal disease, oncogenic osteomalacia, Chinese herbs nephropathy, and Balkan endemic nephropathy. Though poorly understood, FS may be associated with HIV disease and antiretroviral treatment; cadmium poisoning may cause FS. In addition to FS, uRBP4 measurement has a different role: the early detection of acute kidney injury. Urine RBP4 comprises several isoforms, including intact plasma RBP4, MW 21.07 kDa, and C-terminal truncated forms, des-L- and des-LL-RBP4, also probably plasma derived. In FS, uRBP4 levels are about 10(4)-fold above the upper limit of normal and small increments are frequently seen in carriers of some inherited forms of FS and in acquired disease. The very high levels in disease, frequent assay nonlinearity, lack of defined calibrants, and multiple uRBP4 isoforms make accurate assay challenging; top-down mass spectrometry has brought advances. Assays for uRBP4 with defined molecular targets allowing good interlaboratory comparisons are needed.
引用
收藏
页码:85 / 122
页数:38
相关论文
共 162 条
[1]   Urine High and Low Molecular Weight Proteins One-Year Post-Kidney Transplant: Relationship to Histology and Graft Survival [J].
Amer, H. ;
Lieske, J. C. ;
Rule, A. D. ;
Kremers, W. K. ;
Larson, T. S. ;
Palacios, C. R. Franco ;
Stegall, M. D. ;
Cosio, F. G. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2013, 13 (03) :676-684
[2]  
[Anonymous], CRYST REF HUM SER RE
[3]   Renal Effects of Exposure to Natural and Depleted Uranium: A Review of the Epidemiologic and Experimental Data [J].
Arzuaga, Xabier ;
Rieth, Susan H. ;
Bathija, Ambika ;
Cooper, Glinda S. .
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS, 2010, 13 (7-8) :527-545
[4]   Urinary biomarkers in septic acute kidney injury [J].
Bagshaw, Sean M. ;
Langenberg, Christoph ;
Haase, Michael ;
Wan, Li ;
May, Clive N. ;
Bellomo, Rinaldo .
INTENSIVE CARE MEDICINE, 2007, 33 (07) :1285-1296
[5]   Urinary retinol binding protein in Indo-Asian patients with idiopathic interstitial nephritis [J].
Ball, ST ;
Lapsley, M ;
Norden, AGW ;
Cairns, TDH ;
Palmer, ABD ;
Taube, DH .
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, 2003, 96 (05) :363-367
[6]  
Batuman V, 2007, CONTRIB NEPHROL, V153, P87
[7]   Vitamin A deficiency associated with urinary retinol binding protein wasting in Dent's disease [J].
Becker-Cohen, Rachel ;
Rinat, Choni ;
Ben-Shalom, Efrat ;
Feinstein, Sofia ;
Ivgi, Heftziba ;
Frishberg, Yaacov .
PEDIATRIC NEPHROLOGY, 2012, 27 (07) :1097-1102
[8]  
Bergeron M., 2006, SCRIVERS ONLINE META
[9]   Renal dysfunction induced by cadmium: biomarkers of critical effects [J].
Bernard, A .
BIOMETALS, 2004, 17 (05) :519-523
[10]   EFFECT OF RENAL-INSUFFICIENCY ON THE CONCENTRATION OF FREE RETINOL-BINDING PROTEIN IN URINE AND SERUM [J].
BERNARD, A ;
VYSKOCYL, A ;
MAHIEU, P ;
LAUWERYS, R .
CLINICA CHIMICA ACTA, 1988, 171 (01) :85-93