Methods and compositions for diagnosis and prognosis of renal injury and renal failure

Patent metadata

Field	Value
Publication number	US-2022187319-A1
Application number	US-202217681493-A
Country	US
Kind code	A1
Filing date	Feb 25, 2022
Priority date	Dec 20, 2009
Publication date	Jun 16, 2022
Grant date	—

Abstract

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a plurality of assays, one or more of which is configured to detect a kidney injury marker selected from the group consisting of Hyaluronic acid, Immunoglobulin A, Immunoglobulin G1, Immunoglobulin G2, Insulin-like growth factor-binding protein 7, Alpha-1 antitrypsin, Serum amyloid P component, Metalloproteinase inhibitor 2, Hepatocyte growth factor, Intercellular adhesion molecule 1, Beta-2-glycoprotein 1, Interleukin-1 beta, Neutrophil Elastase, Tumor necrosis factor receptor superfamily member HB, Interleukin-11, Cathepsin D, C-C motif chemokine 24, C-X-C motif chemokine 6, C-C motif chemokine 13, C-X-C motif chemokines-1, -2, and -3, Matrilysin, Interleukin-2 receptor alpha chain, Insulin-like growth factor-binding protein 3, and Macrophage colony-stimulating factor 1 as diagnostic and prognostic biomarkers in renal injuries.

First claim

We claim:

1 . A method for evaluating renal status in a subject, comprising:
performing a plurality of assays configured to detect a plurality of kidney injury markers selected from the group consisting of Hyaluronic acid, Immunoglobulin A, Immunoglobulin G1, Immunoglobulin G2, Insulin-like growth factor-binding protein 7, Alpha-1 antitrypsin, Serum amyloid P component, Metalloproteinase inhibitor 2, Hepatocyte growth factor, Intercellular adhesion molecule 1, Beta-2-glycoprotein 1, Interleukin-1 beta, Neutrophil Elastase, Tumor necrosis factor receptor superfamily member 11B, Interleukin-11, Cathepsin D, C-C motif chemokine 24, C-X-C motif chemokine 6, C-C motif chemokine 13, C-X-C motif chemokines-1, -2, and -3, Matrilysin, Interleukin-2 receptor alpha chain, Insulin-like growth factor-binding protein 3, and Macrophage colony-stimulating factor 1 on a body fluid sample obtained from the subject to provide one or more assay results; and correlating the assay results to the renal status of the subject.

2 . A method according to claim 1 , wherein said correlation step comprises correlating the assay results to one or more of risk stratification, diagnosis, staging, prognosis, classifying and monitoring of the renal status of the subject.

3 . A method according to claim 1 , wherein said correlating step comprises assigning a likelihood of one or more future changes in renal status to the subject based on the assay results.

4 . A method according to claim 3 , wherein said one or more future changes in renal status comprise one or more of a future injury to renal function, future reduced renal function, future improvement in renal function, and future acute renal failure (ARF).

5 . A method according to one of claims 1 - 4 , wherein said assay results comprise at least 2, 3, 4, or 5 of:
a measured concentration of Hyaluronic acid, a measured concentration of Immunoglobulin A, a measured concentration of Immunoglobulin G1, a measured concentration of Immunoglobulin G2, a measured concentration of Insulin-like growth factor-binding protein 7, a measured concentration of Alpha-1 antitrypsin, a measured concentration of Serum amyloid P component, a measured concentration of Metalloproteinase inhibitor 2, a measured concentration of Hepatocyte growth factor, a measured concentration of Beta-2-glycoprotein 1, a measured concentration of Interleukin-1 beta, a measured concentration of Intercellular adhesion molecule 1, a measured concentration of Neutrophil Elastase, a measured concentration of Tumor necrosis factor receptor superfamily member 11B, a measured concentration of Interleukin-11, a measured concentration of Cathepsin D, a measured concentration of C-C motif chemokine 24, a measured concentration of C-X-C motif chemokine 6, a measured concentration of C-C motif chemokine 13, a measured concentration of C-X-C motif chemokines-1, -2, and -3, a measured concentration of Matrilysin, a measured concentration of Interleukin-2 receptor alpha chain, a measured concentration of Insulin-like growth factor-binding protein 3, and a measured concentration of and Macrophage colony-stimulating factor 1.

6 . A method according to one of claims 1 - 5 , wherein said assay results are combined using a function that converts said assay results into a single composite result.

7 . A method according to claim 3 , wherein said one or more future changes in renal status comprise a clinical outcome related to a renal injury suffered by the subject.

8 . A method according to claim 3 , wherein the likelihood of one or more future changes in renal status is that an event of interest is more or less likely to occur within 30 days of the time at which the body fluid sample is obtained from the subject.

9 . A method according to claim 8 , wherein the likelihood of one or more future changes in renal status is that an event of interest is more or less likely to occur within a period selected from the group consisting of 21 days, 14 days, 7 days, 5 days, 96 hours, 72 hours, 48 hours, 36 hours, 24 hours, and 12 hours.

10 . A method according to one of claims 1 - 5 , wherein the subject is selected for evaluation of renal status based on the pre-existence in the subject of one or more known risk factors for prerenal, intrinsic renal, or postrenal ARF.

11 . A method according to one of claims 1 - 5 , wherein the subject is selected for evaluation of renal status based on an existing diagnosis of one or more of congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, hypertension, coronary artery disease, proteinuria, renal insufficiency, glomerular filtration below the normal range, cirrhosis, serum creatinine above the normal range, aneurism, congestive heart failure, preeclampsia, eclampsia, diabetes mellitus, coronary artery disease, proteinuria, renal insufficiency, chronic lung disease, acute lung injury, HIV infection, volume depletion, hypotension, shock, sepsis, injury to renal function, reduced renal function, ARF; or based on undergoing or having undergone major vascular surgery, coronary artery bypass, or other cardiac surgery; or based on previous or anticipated exposure to one or more nephrotoxic agents; or one or more risk scores.

12 . A method according to one of claims 1 - 5 , wherein said correlating step comprises assigning a diagnosis of the occurrence or nonoccurrence of one or more of an injury to renal function, reduced renal function, or ARF to the subject based on the assay result(s).

13 . A method according to one of claims 1 - 5 , wherein said correlating step comprises assessing whether or not renal function is improving or worsening in a subject who has suffered from an injury to renal function, reduced renal function, or ARF based on the assay result(s).

14 . A method according to one of claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of an injury to renal function in said subject.

15 . A method according to one of claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of reduced renal function in said subject.

16 . A method according to one of claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of acute renal failure in said subject.

17 . A method according to one of claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of a need for renal replacement therapy in said subject.

18 . A method according to one of claims 1 - 5 , wherein said method is a method of diagnosing the occurrence or nonoccurrence of a need for renal transplantation in said subject.

19 . A method according to one of claims 1 - 5 , wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of an injury to renal function in said subject.

20 . A method according to one of claims 1 - 5 , wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of reduced renal function in said subject.

21 . A method according to one of claims 1 - 5 , wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of acute renal failure in said subject.

22 . A method according to one of claims 1 - 5 , wherein said method is a method of assigning a risk of the future occurrence or nonoccurrence of a need for renal replacement therapy in said subject.

23 . A method according

Assignees

• Astute Medical Inc

Inventors

• Anderberg Joseph
• Gray Jeff
• Mcpherson Paul
• Nakamura Kevin
• Kampf James Patrick

Classifications

• G01N33/53

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title

• G01N33/6893 Primary

  related to diseases not provided for elsewhere · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N2800/347

  Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy · CPC title