Methods for prognosis of future acute renal injury and acute renal failure

Patent metadata

Field	Value
Publication number	US-10830773-B2
Application number	US-201013517244-A
Country	US
Kind code	B2
Filing date	Dec 20, 2010
Priority date	Dec 20, 2009
Publication date	Nov 10, 2020
Grant date	Nov 10, 2020

Abstract

The present invention relates to methods 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 one or more markers selected from the group consisting of Insulin-like growth factor-binding protein 7 and Metalloproteinase inhibitor 2 as diagnostic and prognostic biomarkers in renal injuries.

First claim

We claim:

1. A method of treating a subject at risk of having acute kidney injury, comprising:
obtaining a body fluid sample from the subject;
performing a first analyte binding assay configured to detect a level of Insulin-like growth factor-binding protein 7 in the sample to generate a first assay result and a second analyte binding assay configured to detect a level of Metalloproteinase inhibitor 2 in the sample to generate a second assay result;
combining the first and second assay results using a function that converts the first and second assay results into a single composite result; correlating the single composite result to an increased risk of the subject having acute kidney injury within 72 hours of the time at which the sample is obtained when the single composite result is above a predetermined threshold; and
treating the subject having an increased risk of having acute kidney injury within 72 hours with a compatible treatment regimen, wherein the compatible treatment regimen comprises one or more of initiating renal replacement therapy, withdrawing delivery of compounds that are known to be damaging to the kidney, delaying procedures that are known to be damaging to the kidney and modifying diuretic administration.

2. The method according to claim 1 , wherein the subject is selected for evaluation based on a determination that the subject is at risk of injury to renal function, reduced renal function, improvement in renal function, or acute kidney injury.

3. The method according to claim 1 , wherein said first and second assay results comprise a measured concentration of Insulin-like growth factor-binding protein 7, and a measured concentration of Metalloproteinase inhibitor 2, respectively.

4. The method according to claim 3 , wherein said function that converts said assay results into a single composite result is a multiplication of the first and second assay results.

5. The 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 acute kidney injury.

6. The 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, aneurism, chronic lung disease, acute lung injury, HIV infection, volume depletion, hypotension, shock, sepsis, injury to renal function, reduced renal function, or acute kidney injury; 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 based on one or more risk scores.

7. The method according to claim 1 , 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 acute kidney injury based on the composite result.

8. The method according to claim 1 , wherein said correlating step comprises correlating the composite result to an increased risk of the subject having acute kidney injury within 48 hours of the time at which the sample is obtained.

9. The method according to claim 1 , wherein said correlating step comprises correlating the composite result to an increased risk of the subject having acute kidney injury within 24 hours of the time at which the sample is obtained.

10. The method according to claim 1 , wherein said correlating step comprises correlating the composite result to an increased risk of the subject having acute kidney injury within 12 hours of the time at which the sample is obtained.

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

12. The method according to claim 11 , wherein the subject is in RIFLE stage R.

13. The method according to claim 1 , wherein the subject is in RIFLE stage 0, R, or I.

14. The method according to claim 1 , wherein the subject does not have acute kidney injury.

15. The method according to claim 1 , wherein the increased risk of having acute kidney injury within 72 hours is the increased risk of having future acute kidney injury.

16. A method of testing a subject at risk of having or developing acute kidney injury comprising: obtaining a body fluid sample from the subject; performing a first assay configured to detect a level of Insulin-like growth factor-binding protein 7 within the sample; and performing a second assay configured to detect a level of Metalloproteinase inhibitor 2 in the sample.

17. The method of claim 16 , wherein the sample is obtained within 7 days after an acute medical event which predisposes the subject for developing acute kidney injury, wherein the acute medical event comprises shock, sepsis, hemorrhage, an ischemic surgery, increased intra-abdominal pressure with acute decompensated heart failure, ischemia, pulmonary embolism, pancreatitis, a burn, or excess diuresis.

18. The method of claim 16 , wherein the sample is obtained within 7 days after an acute medical event which predisposes the subject for developing acute kidney injury, wherein the acute medical event comprises exposure to NSAIDs, cyclosporines, tacrolimus, aminoglycosides, foscarnet, ethylene glycol, hemoglobin, myoglobin, ifosfamid, heavy metals, methotrexate, radiopaque contrast media, or streptozotocin.

19. The method of claim 16 , further comprising measuring a volume of urine output, urine flow rate, serum creatinine, or urine creatinine within 7 days after the sample is obtained.

20. The method of claim 16 , further comprising: obtaining a second body fluid sample from the subject within 7 days from the obtaining the first sample; performing a third assay configured to detect a level of Insulin-like growth factor-binding protein 7 within the second sample; and performing a fourth assay configured to detect a level of Metalloproteinase inhibitor 2 in the second sample.

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 Primary

  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

• 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

• G01N33/53

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title