Biomarkers related to organ function

Patent metadata

Field	Value
Publication number	US-12259397-B2
Application number	US-202016823842-A
Country	US
Kind code	B2
Filing date	Mar 19, 2020
Priority date	Sep 23, 2013
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

Disclosed herein are methods of identifying biomarkers (such as genes (e.g., RNA or mRNA), proteins, and/or small molecules) that can be used to predict organ or tissue function or dysfunction. In some embodiments, the methods include ex vivo perfusion of the organ or tissue, collection of samples from the organ or tissue (for example, perfusate, fluids produced by the organ (such as bile or urine), or tissue biopsies) and measuring the level of one or more biomarkers in the sample. It is also disclosed herein that an analysis of biomarkers (such as genes (e.g., RNA or mRNA), proteins, and/or small molecules) present in a biological sample from an organ, tissue, or subject can be used to identify whether the organ, tissue, or subject is at risk for (or has) organ dysfunction or organ failure.

First claim

We claim:

1. A method for identifying organ dysfunction, comprising:
measuring an amount of one or more biomarkers from a biological sample obtained from an organ undergoing machine perfusion, wherein the one or more biomarkers comprise ribulose, ribose, glycolate, oxidized homo-glutathione (GSSG), and ethanolamine;
comparing the amount of the ribulose, ribose, glycolate, oxidized homo-glutathione (GSSG), and ethanolamine to the amount of ribulose, ribose, glycolate, oxidized homo-glutathione (GSSG), and ethanolamine in a control sample or reference value;
determining that the amount of ribose, ribulose, and glycolate is decreased compared to the control sample or reference value and the amount of GSSG and ethanolamine is increased compared to the control sample or reference value and is an indicator of organ dysfunction;
utilizing the amount of ribulose, ribose, glycolate, GSSG, and ethanolamine to select the organ undergoing machine perfusion when the amount of ribose, ribulose, glycolate, GSSG and ethanolamine is a predictor of organ function; and
transplanting the selected organ into a transplant recipient.

2. The method of claim 1 , wherein the sample from the organ comprises a tissue sample, a perfusate from the organ, or a fluid produced by the organ.

3. The method of claim 1 , wherein the organ is a liver, a kidney, a lung, a heart, a pancreas, a small intestine, a limb, an extremity, or a portion of any one thereof.

4. The method of claim 1 , wherein the organ is being evaluated for its viability following transplantation into a subject.

5. The method of claim 1 , wherein the organ is undergoing machine perfusion with a perfusion solution comprising a hemoglobin-based oxygen carrier.

6. The method of claim 5 , wherein the perfusion solution comprises about 3-4 g/dL cross-linked hemoglobin, 25-30 mM NaCl, 1-2 mM KCl, 17-19 mM KH 2 PO 4 , 55-65 mM sodium gluconate, 6-8 mM sodium lactate, 3-4 mM magnesium gluconate, 0.6-0.8 mM CaCl 2 ) dihydrate, 15-16 mM NaOH, 3-4 mM adenine, 6-8 mM dextrose, 2-3 mM glutathione, 6-8 mM HEPES, 3-4 mM ribose, 20-25 mM mannitol, 35-40 g/L hydroxyethyl starch, and 40-60 mg/dL N-acetyl-L-cysteine.

7. The method of claim 1 , wherein the control sample or reference value comprise one or more organs that are known to have organ dysfunction.

8. The method of claim 1 , wherein the control sample or reference value comprise one or more organs that are known not to have organ dysfunction.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Chaves Fontes Paulo Artur
• Kellum John A

Classifications

• G01N2800/60

  Complex ways of combining multiple protein biomarkers for diagnosis · CPC title

• G01N2800/50

  Determining the risk of developing a disease · CPC title

• G01N2800/085

  Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin · CPC title

• G01N2570/00

  Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes · CPC title

• G01N2333/57

  IFN-gamma · CPC title