FULL PAPER Internal Medicine
Urinary albumin and transferrin as early diagnostic markers of chronic kidney disease Hiroto MAEDA1), Kazuyuki SOGAWA2)*, Kazuko SAKAGUCHI3), Saori ABE1), Wataru SAGIZAKA3), Shunsuke MOCHIZUKI4), Waka HORIE1), Toshifumi WATANABE4), Yui SHIBATA2), Mamoru SATOH5), Akihiro SANDA2), Fumio NOMURA5) and Jun SUZUKI3) 1)Maeda
Veterinary Hospital, 1–4–8 Yamatemachi, Tomakomai, Hokkaido 053–0851, Japan of Biochemistry, School of Life and Environmental Science, Azabu University, 1–17–71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252–5201, Japan 3)Department of Food Biochemistry, School of Life and Environmental Science, Azabu University, 1–17–71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252–5201, Japan 4)Veterinary Teaching Hospital, Azabu University, 1–17–71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252–5201, Japan 5)Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, 1–8–1 Inohana, Chuo-ku, Chiba, Chiba 260–8677, Japan 2)Department
(Received 19 August 2014/Accepted 16 March 2015/Published online in J-STAGE 28 March 2015) ABSTRACT.
Feline renal diseases are increasingly noted in veterinary practice. It is important to diagnose and identify the pathological basis of renal dysfunction accurately at an early stage, but there are only a few reports on this area in clinical veterinary medicine. We investigated the efficacy of measurement of urinary albumin (u-Alb) and urinary transferrin (u-Tf) for early diagnosis using 5-µl urine samples collected noninvasively by catheterization from normal (IRIS stage I) cats and cats with stage I chronic kidney disease (CKD). The u-Alb levels in normal and stage I CKD cats were 6.0 ± 4.5 and 11.2 ± 8.4 mg/dl, respectively, and the u-Tf levels were 0.09 ± 0.42 and 0.52 ± 0.79 mg/ dl, respectively. Based on ROC curve analysis, the sensitivity and specificity of u-Alb and u-Tf were higher than those of the currently used biomarker, the plasma creatinine level. The sensitivity of u-Alb was higher than that of u-Tf, whereas the specificity of u-Tf was higher than that of u-Alb. The validity of the threshold albumin level (20 mg/dl) was confirmed by measurements using SDS-PAGE. Since leakage of u-Tf in urine precedes leakage of u-Alb, inclusion of u-Tf in biochemistry tests may be appropriate for IRIS staging as a diagnostic marker of early diagnosis of renal disorder in cats. KEY WORDS: albumin, chronic kidney disease, feline, transferrin, urine doi: 10.1292/jvms.14-0427; J. Vet. Med. Sci. 77(8): 937–943, 2015
Feline renal diseases are increasingly noted in veterinary practice [16]. It is important to diagnose and identify the pathological basis of renal dysfunction accurately at an early stage. Early diagnosis and initiation of treatment of renal dysfunction delay progression of the disease, which leads to prolongation of the survival time and improvement of QOL [7]. But, there are only a few reports on this area in clinical veterinary medicine [18]. In veterinary practice, diseases are classified based on the plasma creatinine level (p-Cre) following the disease classification criteria established by the International Renal Interest Society (IRIS) [17]. Urinary protein and urinary albumin (u-Alb) tests are performed, but urinary protein positivity may be found regardless of the presence or absence of renal disease. Moreover, the uAlb test uses the method for human u-Alb measurement, and thus, the sensitivity is low, although there is homology *Correspondence to: Sogawa, K., Department of Biochemistry, School of Life and Environmental Science, Azabu University, 1–17– 71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252–5201, Japan. e-mail:
[email protected] ©2015 The Japanese Society of Veterinary Science This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License .
between the human and feline proteins. For these reasons, a method with high sensitivity and specificity for early-stage evaluation of feline renal dysfunction is required. Transferrin is an iron-transporting protein with a molecular weight similar to that of albumin, but the isoelectric point is different [6]. Therefore, the kinetics of transferrin differ from those of albumin, and thus, abnormal renal function may be evaluated at an early stage by the urinary transferrin (u-Tf). We have previously shown that u-Alb on micro two-dimensional polyacrylamide gel electrophoresis (M2D-PAGE) is useful as a diagnostic marker of early stage feline chronic kidney disease (CKD) and that the u-Alb level in M2DPAGE analysis does not exceed 20 mg/dl in normal cats. In this study, we investigated the efficacy of measurement of u-Alb and u-Tf for early diagnosis using 5-µl urine samples collected noninvasively by catheterization from normal (IRIS stage I) cats and cats with stage I CKD [9]. MATERIALS AND METHODS Animals: Urine samples collected from 31 cats with nephropathy (stage I CKD) brought to Maeda Veterinary Hospital between July 28, 2007 and July 10, 2008 (American Shorthair: 3, Chinchilla: 1, Mix: 27; 15 males and 16 females aged 3–14 years) were used in the study. Urine samples col-
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lected from 92 cats in IRIS stage I aged ≤2 years (Scottish Fold: 1, American Shorthair: 1, Mix: 90; 42 males and 50 females aged 4 months to 2 years) were used as normal controls. Regarding the diagnostic criteria, cats 1.030, UPC
