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Biomarkers in Urine and Use of Creatinine

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General Methods in Biomarker Research and their Applications

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Abstract

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common and profound issues for human health. Functional biomarkers such as serum creatinine (Scr) have been used as diagnostic indexes for AKI and CKD. In AKI, however, kidney damage precedes functional change. Therefore, novel biomarker candidates have been explored using urine sample. Among these candidates, neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, interleukin-18, and kidney injury molecule-1 are well examined in patients with AKI in specific clinical settings. Furthermore, besides albuminuria known as the established biomarker in CKD, the usefulness of these urinary biomarkers in CKD is also being recognized. The general use of urinary biomarkers for AKI and CKD has not been qualified, but the incorporation must help understand the renal condition. Meanwhile, when the alteration in urinary biomarkers is evaluated, the fluctuation of urine volume (UV) should be corrected because the fluctuation causes the varied concentration of urinary biomarkers. Urinary biomarker excretion rate (UBER) corrected by UV itself is known as a gold standard method and is calculated as a product of urinary biomarker concentration and UV, which requires timed urine collection. Alternatively, urinary biomarker-to-creatinine ratio (UBCR) corrected by urinary creatinine is used to substitute UBER and is calculated as a quotient of dividing urinary biomarker concentration by urinary creatinine concentration, for which spot urine is available. In the case that creatinine kinetics is under a nonsteady state, UBCR is influenced in a positive and negative way. As a positive way, the reliability of UBCR to detect kidney damage can be enhanced due to the decreased urinary creatinine. As a negative way, the change of UBCR is offset due to the increased urinary creatinine, resulting in the overlook of kidney damage. Therefore, the influence of the nonsteady state of creatinine on the kinetics should be considered when the alteration in urinary biomarkers is evaluated.

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Abbreviations

ACR:

Albumin-to-Creatinine Ratio

ADQI:

Acute Dialysis Quality Initiative

AER:

Albumin Excretion Rate

AKI:

Acute Kidney Injury

AKIN:

Acute Kidney Injury Network

ARF:

Acute Renal Failure

BUN:

Blood Urea Nitrogen

Ccr:

Creatinine Clearance

Cin:

Inulin Clearance

CKD:

Chronic Kidney Disease

CKD-EPI:

Chronic Kidney Disease Epidemiology Collaboration

CysC:

Cystatin C

ER:

Endoplasmic Reticulum

FA:

Fatty Acid

FABP:

Fatty Acid-Binding Protein

GFcr:

Glomerular-Filtrated Creatinine

GFin:

Glomerular-Filtrated Inulin

GFR:

Glomerular Filtration Rate

IL18:

Interleukin-18

KDIGO:

Kidney Disease: Improving Global Outcomes

KIM-1:

Kidney Injury Molecule-1

L-FABP:

Liver-Type Fatty Acid-Binding Protein

MATE1:

Multidrug and Toxin Extrusion-1

MDRD:

Modification of Diet in Renal Disease

NGAL:

Neutrophil Gelatinase-Associated Lipocalin

OAT:

Organic Anion Transporter

OCT2:

Organic Cation Transporter-2

Scr:

Serum Creatinine

Sin:

Serum Inulin

TScr:

Tubular-Secreted Creatinine

UBCR:

Urinary Biomarker-to-Creatinine Ratio

UBER:

Urinary Biomarker Excretion Rate

UBM:

Urinary Biomarker

Ucr:

Urinary Creatinine

Uin:

Urinary Inulin

UV:

Urine Volume

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Authors and Affiliations

  1. Drug Safety Evaluation, Research Laboratories for Development, Shionogi & Co., Ltd., 3-1-1, Futabacho, 561-0825, Toyonaka, Osaka, Japan

    Yutaka Tonomura

  2. Division of Molecular Medicine, Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, 2-1, Seiryomachi, Aoba-ku, 980-8575, Sendai, Miyagi, Japan

    Mitsunobu Matsubara

  3. Department of Physiology I, Tohoku University Graduate School of Medicine, 2-1, Seiryomachi, Aoba-ku, 980-8575, Sendai, Miyagi, Japan

    Itsuro Kazama

Authors
  1. Yutaka Tonomura
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  2. Mitsunobu Matsubara
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  3. Itsuro Kazama
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Correspondence to Yutaka Tonomura .

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Editors and Affiliations

  1. Department of Nutrition and Dietetics, Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom

    Victor R. Preedy

  2. Faculty of Science & Technology, Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Tonomura, Y., Matsubara, M., Kazama, I. (2015). Biomarkers in Urine and Use of Creatinine. In: Preedy, V., Patel, V. (eds) General Methods in Biomarker Research and their Applications. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7696-8_18

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