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-11353465-B2
Application number	US-201816475326-A
Country	US
Kind code	B2
Filing date	Jan 12, 2018
Priority date	Jan 12, 2017
Publication date	Jun 7, 2022
Grant date	Jun 7, 2022

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 as a rule-in for persistent AKI-when the assay result is above a predetermined threshold and the threshold provides a positive predictive value of at least 0.6; and
treating the subject having persistent AKI with renal replacement therapy (RRT).

2. The method of claim 1 , wherein the body fluid is urine, blood, serum, or plasma.

3. The method of claim 1 , 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 the body fluid sample is obtained to 48 hours after the body fluid sample is obtained.

4. The method of claim 1 , 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.

5. The method of claim 1 , wherein the RRT comprises hemodialysis.

6. The method of claim 1 , wherein
(a) the threshold provides a positive predictive value of at least 0.75 for persistent AKI; or
(b) the threshold provides a positive predictive value of at least 0.8 for persistent AKI.

7. 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 as a rule-in for persistent AKI when the assay result is above a predetermined threshold and the threshold provides a positive predictive value of at least 0.6; and
treating the subject having persistent AKI with renal replacement therapy (RRT).

8. The method of claim 7 , 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, Liver Fatty acid-binding protein, Creatinine, including combinations thereof.

9. The method of claim 7 , wherein the body fluid is urine, blood, serum, or plasma.

10. The method of claim 9 , wherein said assay result is a measured urine concentration of C-C motif chemokine 14.

11. The method of claim 7 , 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 the body fluid sample is obtained to 48 hours after the time the body fluid sample is obtained.

12. The method of claim 7 , wherein the RRT comprises hemodialysis.

13. The method of claim 7 , wherein
(a) the threshold provides a positive predictive value of at least 0.75 for persistent AKI; or
(b) the threshold provides a positive predictive value of at least 0.8 for persistent AKI.

14. The method of claim 2 , wherein the assay result is a measured urine concentration of C-C motif chemokine 14.

15. The method of claim 1 , 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.

16. The method of claim 7 , 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.

Assignees

• Astute Medical Inc

Inventors

• Kampf James Patrick
• Mcpherson Paul
• Chalfin Donald

Classifications

• 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

• 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