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

Patent metadata

Field	Value
Publication number	US-10324093-B2
Application number	US-201013508363-A
Country	US
Kind code	B2
Filing date	Nov 5, 2010
Priority date	Nov 7, 2009
Publication date	Jun 18, 2019
Grant date	Jun 18, 2019

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 one or more assays configured to detect a kidney injury marker selected from the group consisting of Cathepsin B, Renin, Dipeptidyl Peptidase IV, Neprilysin, Beta-2-microglobulin, Carbonic anhydrase IX, and C-X-C motif chemokine 2 as diagnostic and prognostic biomarkers in renal injuries.

First claim

We claim:

1. A method for evaluating and treating renal status in a subject, comprising:
obtaining a body fluid sample from a subject selected for evaluation based on a determination that the subject is at risk of a future or current acute renal injury;
performing an analyte binding assay configured to detect C-X-C motif chemokine 2 by introducing the 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 specific binding reagent which specifically binds C-X-C motif chemokine 2, and (ii) generates an assay result indicative of binding of C-X-C motif chemokine 2 to the specific binding reagent;
displaying the assay result generated by the assay instrument in a human-readable form; and
correlating the assay result to the renal status of the subject by assigning the subject to a predetermined subpopulation of individuals having a known predisposition of a future acute renal injury, the assignment made by comparing the assay result or a value derived therefrom to a threshold value obtained from a population study, wherein the threshold separates the population into a first subpopulation above the threshold which is at an increased predisposition for future acute renal injury meeting the definition of RIFLE I or F within 48 hours of the time the body fluid sample is obtained relative to a second subpopulation below the threshold; and
treating the subject based on the predetermined subpopulation of individuals to which the subject is assigned, wherein when the assay result or value derived therefrom is above the threshold value, the subject is treated by one or more of initiating renal replacement therapy, withdrawing delivery of compounds that are known to be damaging to the kidney, delaying or avoiding procedures that are known to be damaging to the kidney, and modifying diuretic administration.

2. A method according to claim 1 , wherein a plurality of assay results for a plurality of biomarkers, one of which plurality of assay results is the assay result indicative of binding of C-X-C motif chemokine 2 to the specific binding reagent, are combined using a function that converts the plurality of assay results into a single composite result, and the assay results displayed in human readable form comprise the single composite result.

3. A method according to claim 1 , 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.

4. A method according to claim 1 , 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, sepsis, injury to renal function, reduced renal function, or ARF, or based on undergoing or having undergone major vascular surgery, coronary artery bypass, or other cardiac surgery, or based on exposure to NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamide, heavy metals, methotrexate, radiopaque contrast agents, or streptozotocin.

5. A method according to claim 1 , wherein the threshold separates the population into a first subpopulation above the threshold which is at an increased predisposition for future acute renal injury meeting the definition of RIFLE I or F within 24hours of the time the body fluid sample is obtained relative to a second subpopulation below the threshold.

Assignees

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

Inventors

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

Classifications

• G01N33/6893

  related to diseases not provided for elsewhere · 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

• G01N33/6842 Primary

  Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins · CPC title

• G01N2333/96413

  Cysteine endopeptidases (3.4.22) · CPC title

• G01N2800/56

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