Methods and Compositions for Evaluation and Treatment of Renal Injury and Renal Failure Based on C-C Motif Chemokine Ligand 14 Measurement

Patent metadata

Field	Value
Publication number	US-2019339289-A1
Application number	US-201816475326-A
Country	US
Kind code	A1
Filing date	Jan 12, 2018
Priority date	Jan 12, 2017
Publication date	Nov 7, 2019
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 assays that detect C-C motif chemokine 14 as diagnostic and prognostic biomarker assays in renal injuries.

First claim

We claim:

1 . A method for evaluating renal status in a subject that is diagnosed as having an acute kidney injury, wherein the subject meets the definition RIFLE I or F or KDIGO Stage 2 or 3, and treating the subject based on the evaluation, comprising:
performing an analyte binding assay configured to detect C-C motif chemokine 14 by introducing a body fluid sample obtained from the subject into an assay instrument which (i) contacts all or a portion of the body fluid sample with a binding reagent which specifically binds for detection C-C motif chemokine 14 and (ii) generates an assay result indicative of binding of C-C motif chemokine 14 to the binding reagent; correlating the assay result generated by the assay instrument to a likelihood that the subject has a persistent acute kidney injury (AKI) by using the assay result to assign the subject to a predetermined subpopulation of individuals having a known predisposition persistent AKI, the assignment made by comparing the assay result or a value derived therefrom to a threshold selected in a population study, wherein the threshold separates the population into a first subpopulation above the threshold which is at an increased predisposition for having persistent AKI relative to a second subpopulation below the threshold; and treating the subject based on the predetermined subpopulation of individuals to which the human subject is assigned, wherein the correlation is used as a rule-in test for persistent AKI and if the assay result or the value derived therefrom is above the threshold, the subject's AKI is treated with renal replacement therapy (RRT), or wherein the correlation is used as a rule-out test for persistent AKI and if the assay result or the value derived therefrom is below the threshold, the subject's AKI is treated conservatively.

2 . A method according to claim 1 , wherein the correlating step comprises comparing the assay result or a value derived therefrom to at least two thresholds, the first of which is used in the rule-in test for persistent AKI and if the assay result or the value derived therefrom is above the first threshold, the subject's AKI is treated with renal replacement therapy, and the second of which is used in the rule-out test for persistent AKI and if the assay result or the value derived therefrom is below second first threshold, the subject's AKI is treated conservatively.

3 . A method according to claim 1 or 2 , wherein the body fluid is urine, blood, serum, or plasma.

4 . A method according to claim 3 , wherein said assay result is a measured urine concentration of C-C motif chemokine 14.

5 . A method according to one of claims 1 - 4 , wherein a persistent AKI is defined as acute kidney injury meeting the definition RIFLE I or F or KDIGO Stage 2 or 3 for 72 hours, where the persistence period begins from the time of sample collection to 48 hours after sample collection.

6 . A method according to one of claims 1 - 4 , wherein a persistent AKI is defined as acute kidney injury meeting the definition RIFLE F or KDIGO Stage 3 for 72 hours, where the persistence period begins from the time the body fluid sample is obtained to 48 hours after the time the body fluid sample is obtained.

7 . A method according to one of claims 1 - 6 , wherein the subject is diagnosed as having an acute kidney injury meeting the definition RIFLE F or KDIGO Stage 3 at the time the time the body fluid sample is obtained.

8 . A method according to one of claims 1 - 7 , wherein the RRT comprises hemodialysis.

9 . A method according to one of claims 1 - 8 , wherein the correlation is used as a rule in test for persistent AKI, and the threshold provides a positive predictive value of at least 0.6 for persistent AKI.

10 . A method according to claim 9 , wherein the threshold provides a positive predictive value of at least 0.75 for persistent AKI.

11 . A method according to claim 9 , wherein the threshold provides a positive predictive value of at least 0.8 for persistent AKI.

12 . A method according to one of claims 1 - 8 , wherein the correlation is used as a rule out test for persistent AKI, and the threshold provides a negative predictive value of at least 0.6 for persistent AKI.

13 . A method according to claim 9 , wherein the threshold provides a negative predictive value of at least 0.75 for persistent AKI.

14 . A method according to claim 9 , wherein the threshold provides a negative predictive value of at least 0.8 for persistent AKI.

15 . A method for evaluating renal status in a subject and treating the subject based on the evaluation, comprising:
selecting the subject for evaluation based on a measured value of one or more AKI biomarkers that exceeds a threshold indicative of an increased risk of having an acute kidney injury that meets the definition RIFLE I or F or KDIGO Stage 2 or 3; performing an analyte binding assay configured to detect C-C motif chemokine 14 by introducing a body fluid sample obtained from the subject into an assay instrument which (i) contacts all or a portion of the body fluid sample with a binding reagent which specifically binds for detection C-C motif chemokine 14 and (ii) generates an assay result indicative of binding of C-C motif chemokine 14 to the binding reagent; correlating the assay result generated by the assay instrument to a likelihood that the subject has a persistent acute kidney injury (AKI) by using the assay result to assign the subject to a predetermined subpopulation of individuals having a known predisposition persistent AKI, the assignment made by comparing the assay result or a value derived therefrom to a threshold selected in a population study, wherein the threshold separates the population into a first subpopulation above the threshold which is at an increased predisposition for having persistent AKI relative to a second subpopulation below the threshold; and treating the subject based on the predetermined subpopulation of individuals to which the human subject is assigned, wherein the correlation is used as a rule-in test for persistent AKI and if the assay result or the value derived therefrom is above the threshold, the subject's AKI is treated with renal replacement therapy (RRT), or wherein the correlation is used as a rule-out test for persistent AKI and if the assay result or the value derived therefrom is below the threshold, the subject's AKI is treated conservatively.

16 . A method according to claim 15 , wherein the AKI biomarkers are one or more of Insulin-like growth factor-binding protein 7, Metalloproteinase inhibitor 2, Neutrophil gelatinase-associated lipocalin, Cystatin-C, Interleukin-18, Hepatitis A virus cellular receptor 1, Glutathione S-transferase P, Fatty acid-binding protein, liver, Creatinine, including combinations thereof.

17 . A method according to claim 15 , wherein the measured value is calculated by multiplying an Insulin-like growth factor-binding protein 7 concentration and a Metalloproteinase inhibitor 2 concentration.

18 . A method according to one of claims 15 - 17 , wherein the correlating step comprises comparing the assay result or a value derived therefrom to at least two thresholds, the first of which is used in the rule-in test for persistent AKI and if the assay result or the value derived therefrom is above the first threshold, the subject's AKI is treated with renal replacement therapy, and the second of which is used in the rule-out test for persistent AKI and if the assay result or the value derived therefrom is below second first threshold, the subject'

Assignees

• Astute Medical Inc

Inventors

• Kampf James Patrick
• Mcpherson Paul
• Chalfin Donald

Classifications

• G01N2800/347

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

• G01N2333/521

  Chemokines · CPC title

• G01N2800/56

  Staging of a disease; Further complications associated with the disease · 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