US 10,300,108 B2Granted

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

AssigneesAstute Medical, Inc., University of Pittsburgh—Of the Commonwealth System of Higher Education

InventorsPaul McPherson, John A. Kellum

Life of this patent

Estimating the term…

Loading patent…

Abstract

It is an object of the present invention to provide methods and compositions for protection of subjects from acute kidney injury by treating the subject with compounds that modulate the cell cycle. Modulating the cell cycle can comprise inducing G0/G1 cell cycle arrest, and/or inducing cell cycle progression. As demonstrated below, even a single administration of a compound which induces G0/G1 cell cycle arrest can protect subjects from AKI, and may be used prophylactically in advance of, or as a treatment following, various treatments or conditions that are known to be injurious to the kidney, followed optionally by release of the arrest. Once AKI is established, cell cycle progression can be induced to increase replacement of lost and damaged cells.

Claims10

Dependent claims

A method of prophylactically treating a subject at risk of an acute kidney injury, comprising:

(i) measuring a Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) level in combination with an Insulin-like Growth Factor Binding Protein-7 (IGFBP7) level in a first body fluid sample obtained from the subject to provide a first TIMP-2 assay result and a first IGFBP7 assay result;
(ii) following obtaining the first body fluid sample, administering an effective amount of one or more agents that modulate G0/G1 cell cycle arrest of renal epithelial cells to the patient for a time sufficient to induce cell cycle arrest in a population of the renal epithelial cells but insufficient to induce nephrotoxicity as measured by progression of the patient to acute renal failure (ARF);
(iii) measuring TIMP-2 and IGFBP7 levels in a second body fluid sample obtained from the subject 24 hours after the administering step to provide a second TIMP-2 assay result and a second IGFBP7 assay result;
comparing the first TIMP-2 assay result to the second TIMP-2 assay result and the first IGFBP7 assay result to the second IGFBP7 assay result, wherein
if the first TIMP-2 assay result is not elevated relative to the second TIMP-2 assay result, and the first IGFBP7 assay result is elevated relative to the second IGFBP7 assay result, identifying the subject as having been successfully treated prophylactically.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/101,118Filed 3 Dec 2014 · us provisional application
Priority: 3 Dec 2013
Published: US 2016/0303187 A120 Oct 2016
Granted: 28 May 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification21 codes

A61K 38/13
Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C: cyclosporins
A61K 31/357
Having oxygen as the only ring hetero atom, e.g. fungichromin: having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
A61K 31/366
Lactones: having six-membered rings, e.g. delta-lactones
A61K 31/436
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a six-membered ring having oxygen as a ring…