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Identification of Diagnostic Urinary Biomarkers for Acute Kidney Injury
  1. Sanju A. Varghese, MD*,
  2. Thomas B. Powell, MD*,
  3. Michael G. Janech, PhD*,
  4. Milos N. Budisavljevic, PhD*†,
  5. Romesh C. Stanislaus, PhD,
  6. Jonas S. Almeida, PhD,
  7. John M. Arthur, MD, PhD*†
  1. From the *Department of Medicine, Division of Nephrology, Medical University of South Carolina; †Department of Medicine, Ralph H. Johnson VA Medical Center, Charleston, SC; and ‡Department of Biostatistics and Applied Mathematics, University of Texas MD Anderson Cancer Center, Houston, TX.
  1. Received August 11, 2009, and in revised form December 7, 2009.
  2. Accepted for publication January 10, 2010.
  3. Reprints: John M. Arthur, MD, PhD, Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC, 96 Jonathan Lucas St, PO Box 250623, Charleston, SC 29425. E-mail: arthurj{at}musc.edu.
  4. Supported by R01DK080234 and with Federal funds as part of the NHLBI Proteomics Initiative from the National Heart, Lung, and Blood Institute, National Institutes of Health, under contract no. N01-HV-28181. Additional support for this project came from the Department of Veterans Affairs.

Abstract

Acute kidney injury (AKI) is an important cause of death among hospitalized patients. The 2 most common causes of AKI are acute tubular necrosis (ATN) and prerenal azotemia (PRA). Appropriate diagnosis of the disease is important but often difficult. We analyzed urine proteins by 2-dimensional gel electrophoresis from 38 patients with AKI. Patients were randomly assigned to a training set, an internal test set, or an external validation set. Spot abundances were analyzed by artificial neural networks to identify biomarkers that differentiate between ATN and PRA. When the trained neural network algorithm was tested against the training data, it identified the diagnosis for 16 of 18 patients in the training set and all 10 patients in the internal test set. The accuracy was validated in the novel external set of patients where conditions of 9 of 10 patients were correctly diagnosed including 5 of 5 with ATN and 4 of 5 with PRA. Plasma retinol-binding protein was identified in 1 spot and a fragment of albumin and plasma retinol-binding protein in the other. These proteins are candidate markers for diagnostic assays of AKI.

Key Words
  • acute kidney injury
  • biomarkers
  • diagnosis
  • kidney
  • urine

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