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

Patent metadata

Field	Value
Publication number	US-9459261-B2
Application number	US-201214241005-A
Country	US
Kind code	B2
Filing date	Aug 24, 2012
Priority date	Aug 26, 2011
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

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 Heat shock 70 kDa protein 1, Alpha-1-antitrypsin Neutrophil elastase complex, Stromelysin-1:Metalloproteinase inhibitor 2 complex, 72 kDa type IV collagenase:Metalloproteinase inhibitor 2 complex, Insulin-like growth factor 1 receptor, Myeloid differentiation primary response protein MyD88, Neuronal cell adhesion molecule, and Tumor necrosis factor ligand superfamily member 10 as diagnostic and prognostic biomarkers in renal injuries.

First claim

We claim:

1. A method for evaluating renal status in a subject, comprising:
performing one or more assays configured to detect Stromelysin-1:Metalloproteinase inhibitor 2 complex, on a body fluid sample obtained from the subject to provide an assay result;
correlating the assay result(s) to the renal status of the subject by introducing the body fluid sample obtained from the subject into an assay instrument which contacts all or a portion of the body fluid sample with a binding reagent which specifically binds for detection Stromelysin-1:Metalloproteinase inhibitor 2 complex, and (ii) generates an assay result indicative of binding of Stromelysin-1:Metalloproteinase inhibitor 2 complex to the binding reagent; and
correlating the assay result generated by the assay instrument to the renal status of the subject by using the assay result to assign the subject to a predetermined subpopulation of individuals having a known predisposition of a future acute renal injury within 72 hours of the time at which the body fluid sample is obtained; and
treating the patient based on the predetermined subpopulation of individuals to which the patient is assigned, wherein the treatment comprises 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 said assay result comprises a measured concentration of Stromelysin-1:Metalloproteinase inhibitor 2 complex.

3. A method according to claim 1 , wherein a plurality of assay results are combined using a function that converts the plurality of assay results into a single composite result.

4. 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.

5. 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.

6. A method according to claim 1 , 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) within 48 hours of the time at which the body fluid sample is obtained.

7. A method according to claim 1 , 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) within 24 hours of the time at which the body fluid sample is obtained.

8. A method according to claim 1 , wherein the subject is in RIFLE stage 0 or R.

9. A method according to claim 8 , wherein the subject is in RIFLE stage 0 or R, and said correlating step comprises assigning a likelihood that the subject will reach RIFLE stage I or F within 72 hours.

10. A method according to claim 1 , wherein the subject is not in acute renal failure.

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P41/00

  Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title