[Frontiers in Bioscience S2, 591-615, January 1, 2010] 591 Clinical biomarkers in kidney diseases Francesca Bonomini 1 , Eleonora Foglio 1 , Luigi Fabrizio Rodella 1 , Rita Rezzani 1 1 Unit of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia TABLE OF CONTENTS 1.Abstract 2.Introduction 3.Acute Renal Failure 3.1.Causes of ARF in the critically ill patient 3.2.Histopathology of ARF 3.3.Epidemiology of ARF 3.4.Definition and classification systems for ARF 3.4.1.RIFLE classification 3.4.2.Modifications of the RIFLE criteria 3.5.Diagnostic approach 3.6.Emerging biomarkers for AKI 3.6.1.Interleukin-18 3.6.2.Neutrophil Gelatinase-Associated Lipocalin 3.6.3.Kidney injury molecule-1 3.6.4.Cystatin C 3.6.5.Fatty Acid-Binding Protein 3.6.6.Other biomarkers 3.6.7.Tubular enzymes and markers of tubular dysfunction 4.Biomarkers for monitoring progression from acute to chronic kidney diseases 5.Chronic Kidney Disease 5.1.Histopathology of CKD 5.2.Emerging biomarkers for CKD 5.2.1.Neutrophil Gelatinase-Associated Lipocalin 5.2.2.Cystatin C 5.2.3.Asymmetric Dimethylarginine 5.2.4.Liver associated- Fatty Acid-Binding Protein 6.Summary and Perspective 7.Ackowledgements 1. ABSTRACT Biomarkers are “biological parameters that can be objectively measured and evaluated, which act as indicators of normal or pathogenic processes, or of the pharmacological response to a therapeutic intervention”.Renal failure can be broadly divided in acute and chronic renal diseases, two classes of renal pathology that are well distinct each other, not only on the basis of duration and reversibility of loss of kidney function, but also because of their different aetiopathological processes and their different histopathological characteristics.Unlikely, the conventional measures used for monitoring kidney function are not ideal in the diagnosis of neither acute or chronic kidney diseases and has impaired our ability to institute potentially effective therapies.Therefore, researchers are seeking new early, predictive, non-invasive biomarkers that can aid in the diagnosis for both acute and chronic diseases.These biomarkers will be useful for assessing the duration and severity of kidney disease, and for predicting progression and adverse clinical outcomes.This review article summarized our current understanding of the acute and chronic renal diseases and discussed the most promising biomarkers for facilitating early detection and predicting clinical outcomes. 2. INTRODUCTION The kidney normally performs a variety of functions essential for the regulation of a constant environment and the maintenance of metabolic homeostasis (1).In order to sustain glomerular filtration and renal metabolism, the renal vascular bed receives a disproportionately large blood flow, averaging 20-25% of resting cardiac output. As a result, cells of the renal vasculature, glomerula, tubules and interstitium are exposed to high volumes of toxicants.The tubular epithelium is especially susceptible to injury, as a result of 1) solute and water reabsorption along the nephron, producing greater concentration of filtered toxicants in the tubular fluid than those seen in the general circulation; 2) transport processes resulting in high intracellular concentration of toxicants and their metabolites; 3) high energy requirements necessary to support epithelial cell metabolism and solute transport.The effects of toxicants on the kidney are protean, with a multitude of different compounds and varying mechanism of injury implicated.Injury may occur secondary to altered renal hemodynamics, direct cellular damage to the tubular epithelium, tubular obstruction of urinary flow due to the precipitation of toxins or their metabolites, interstitial