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US 10,539,575 B2Granted
Biomarkers related to kidney function and methods using the same
AssigneeMetabolon, Inc.
InventorsRegis Perichon, Jeffery Edmond Cobb, Meredith V. Brown, Adam Kennedy
Life of this patent
Estimating the term…
Abstract
Biomarkers of kidney function and methods for using said biomarkers for assessing kidney function, monitoring kidney function, diagnosing acute kidney injury, and diagnosing chronic kidney disease are provided. Also provided are suites of small molecule entities as biomarkers for chronic kidney disease.
Claims17
A method of determining and treating kidney function impairment in a subject, the method comprising:
- a) extracting small molecules from a biological sample obtained from the subject to produce an analytical sample;
- b) performing or having performed an assay on the analytical sample to determine the level(s) of one or more biomarkers, wherein the one or more biomarkers are selected from the group consisting of the following biomarkers:
- N-acetylthreonine, N-acetylalanine, arabitol, N-acetylserine, erythronate, 4-acetamidobutanoate, N6-carbamoylthreonyladenosine, N-acetylcarnosine, arabonate, xylonate, N-formylmethionine, O-methylcatechol sulfate, N-acetylmethionine, N2,N5-diacetylornithine, ribose, pyroglutamine, 5-methylthioadenosine (MTA), 1-methylurate, pro-hydroxy-pro, N-acetyl-3-methylhistidine, 2,3-dihydroxyisovalerate, trigonelline (N′-methylnicotinate), X-11564, and X-17299;
- c) determining kidney function impairment in the subject by comparing the level(s) of the one or more biomarkers in the sample to kidney function reference levels of the one or more biomarkers in order to determine impaired kidney function in the subject;
- and
- d) administering an effective treatment to the subject having impaired kidney function, wherein effective treatment comprises one or more of weight loss, healthy diet, smoking cessation, high blood pressure treatment, performing or having performed dialysis, or performing or having performed a kidney transplant.
3 more elements
A method of preventing impaired kidney function in a subject being considered for treatment with a composition wherein the composition is selected from the group consisting of a chemotherapeutic agent, an antibiotic, and a contrast imaging agent, wherein the composition may have a toxic effect on the kidneys, the method comprising:
- a) extracting small molecules from a biological sample obtained from the subject to produce an analytical sample;
- b) performing, or having performed, an assay on the analytical sample to determine the level(s) of one or more biomarkers, wherein the one or more biomarkers are selected from the group consisting of the following biomarkers:
- N-acetylthreonine, N-acetylalanine, arabitol, N-acetylserine, erythronate, 4-acetamidobutanoate, N6-carbamoylthreonyladenosine, N-acetylcarnosine, arabonate, xylonate, N-formylmethionine, O-methylcatechol sulfate, N-acetylmethionine, N2,N5-diacetylornithine, ribose, pyroglutamine, 5-methylthioadenosine (MTA), 1-methylurate, pro-hydroxy-pro, N-acetyl-3-methylhistidine, 2,3-dihydroxyisovalerate, trigonelline (N′-methylnicotinate), X-11564, and X-17299;
- and
- c) performing or having performed an assay on the analytical sample to determine the level(s) of one or more additional biomarkers selected from the group consisting of the following biomarkers:
- trans-4-hydroxyproline, myo-inositol, kynurenine, tryptophan, 3-methylhistidine, erythritol, urea, 3-methylglutarylcarnitine (C6), S-adenosylhomocysteine (SAH), N1-methyladenosine, N2,N2-dimethylguanosine, p-cresol sulfate, succinylcarnitine, 2-methylbutyrylcarnitine (C5), N4-acetylcytidine, N1-Methyl-2-pyridone-5-carboxamide, 1-methylhistidine, tiglyl carnitine, isobutyrylcarnitine, indolelactate, glutarylcarnitine (C5), choline, hydroxyisovaleroyl carnitine, scyllo-inositol, quinate, salicyluric glucuronide, 2-mannopyranosyl tryptophan (2-MPT), creatinine, phenylacetyl-L-glutamine, 3-indoxylsulfate, pseudouridine, N6-acetyllysine, threitol and 2-hydroxyhippurate (salicylurate);
- and
- d) using the determined levels of the one or more biomarkers and, optionally, the one or more additional biomarkers, in a mathematical model to calculate an estimated glomerular filtration rate (GFR);
- e) using the estimated GFR to determine kidney function in the subject, and
- i. administering the chemotherapeutic agent, antibiotic, and/or contrast imaging agent to the subject having normal kidney function,
- ii. decreasing the dosage of the chemotherapeutic agent, antibiotic, and/or contrast imaging agent or selecting a different chemotherapeutic agent, antibiotic, and/or contrast imaging agent to administer to the subject having moderately impaired kidney function, or
- iii. decreasing the dosage of the chemotherapeutic agent, antibiotic, and/or contrast imaging agent, selecting a different chemotherapeutic agent, antibiotic, and/or contrast imaging agent, or selecting a different treatment intervention or diagnostic test for the subject having severely impaired kidney function.
9 more elements
A method of monitoring kidney function to prevent impaired kidney function in a subject wherein the subject has been treated with a composition that may impair kidney function, wherein the composition is administered to a subject to treat a disease or condition and wherein risk of kidney damage from treatment with the composition for a subject having impaired kidney function is higher than for a subject not having impaired kidney function, the method comprising:
- a) extracting small molecules from a biological sample obtained from a subject treated with a composition that may have a toxic effect on the kidneys;
- b) performing or having performed an assay on a first biological sample from the subject to determine the level(s) of one or more biomarkers for kidney function, where the one or more biomarkers are selected from the group consisting of the following biomarkers:
- N-acetylthreonine, N-acetylalanine, arabitol, N-acetylserine, erythronate, 4-acetamidobutanoate, N6-carbamoylthreonyladenosine, N-acetylcarnosine, arabonate, xylonate, N-formylmethionine, O-methylcatechol sulfate, N-acetylmethionine, N2,N5-diacetylornithine, ribose, pyroglutamine, 5-methylthioadenosine (MTA), 1-methylurate, pro-hydroxy-pro, N-acetyl-3-methylhistidine, 2,3-dihydroxyisovalerate, trigonelline (N′-methylnicotinate), X-11564, and X-17299;
- c) performing or having performed the assay on a second biological sample from the subject to determine the level(s) of the one or more biomarkers for kidney function, wherein the second sample is obtained from the subject at a second time point;
- and
- d) monitoring kidney function in the subject by comparing the level(s) of one or more biomarkers in the second sample to the level(s) of the one or more biomarkers in (a) the first sample and/or (b) kidney function reference levels of the one or more biomarkers, and
- i. continuing to administer the composition to the subject having kidney function that remains in a normal range,
- ii. decreasing the dosage of the composition or selecting a different composition for treating the subject having kidney function that is moderately impaired, or
- iii. discontinuing treatment with the composition and selecting a different composition or treatment regimen;
- or continuing treatment by administering a decreased dosage of the composition to the subject having kidney function that is severely impaired.
7 more elements
A method to determine or aid in the determination of kidney function in a subject who is a potential kidney donor, the method comprising:
- a) extracting small molecules from a biological sample obtained from the subject to produce an analytical sample;
- b) performing or having performed an assay on the analytical sample from the subject to determine the level(s) of one or more biomarkers, wherein the one or more biomarkers are selected from the group consisting of the following biomarkers:
- N-acetylthreonine, N-acetylalanine, arabitol, N-acetylserine, erythronate, 4-acetamidobutanoate, N6-carbamoylthreonyladenosine, N-acetylcarnosine, arabonate, xylonate, N-formylmethionine, O-methylcatechol sulfate, N-acetylmethionine, N2,N5-diacetylornithine, ribose, pyroglutamine, 5-methylthioadenosine (MTA), 1-methylurate, pro-hydroxy-pro, N-acetyl-3-methylhistidine, 2,3-dihydroxyisovalerate, trigonelline (N′-methylnicotinate), X-11564, and X-17299;
- c) using the determined level(s) of the one or more biomarkers in a mathematical model to calculate an estimated glomerular filtration rate (GFR);
- d) using the estimated GFR to determine kidney function of the potential donor, and
- e) performing or having performed a kidney transplant using a kidney of the potential donor having normal kidney function.
3 more elements
Dependencies are inferred from the claim text.