Methods for prevention and treatment of acute renal injury

• US 8,940,696 B2
• Filed: 10/25/2013
• Issued: 01/27/2015
• Est. Priority Date: 02/26/2008
• Status: Active Grant

• Current Assignee: Cornell University
• Original Assignee: Cornell University
• Inventors: Szeto, Hazel H., Felsen, Diane
• Primary Examiner(s): Cordero Garcia, Marcela M
• Application Number:
  US14/063,792
• Publication Number:
  US 20140107033A1
• Time in Patent Office: 459 Days
• US Class Current: 514/15.4
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: C07K 5/1016 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/1019 with the first amino acid being basic

Abstract

The disclosure relates to a method for protecting a kidney from renal injury. For example, acute renal injury may be associated with decreased or blocked blood flow in the subject'"'"'s kidney or exposure to a nephrotoxic agent, such as a radiocontrast dye. The methods include administering to the subject an effective amount of an aromatic-cationic peptide to a subject in need thereof.

Claims

1. A method for protecting a kidney from contrast-induced nephropathy in a subject in need thereof, the method comprising administering to the subject an effective amount of a peptide selected from the group consisting of Phe-D-Arg-Phe-Lys-NH₂ and D-Arg-2′

6′

Dmt-Lys-Phe-NH₂.

2. The method of claim 1, wherein the peptide is Phe-D-Arg-Phe-Lys-NH₂.

3. The method of claim 1, wherein the peptide is D-Arg-2′

6′

Dmt-Lys-Phe-NH₂.

4. The method of claim 1, wherein the contrast-induced nephropathy comprises an inflammatory response.

5. The method of claim 1, wherein the contrast-induced nephropathy comprises a decrease in glomerular filtration rate (GFR) compared to a healthy control subject.

6. The method of claim 1, wherein the contrast-induced nephropathy comprises a decrease in urinary output compared to a healthy control subject.

7. The method of claim 1, wherein the contrast-induced nephropathy comprises an increase in renal tubular apoptosis compared to a healthy control subject.

8. The method of claim 1, wherein the contrast-induced nephropathy comprises loss of renal tubular brush border and/or renal vacuolization.

9. The method of claim 1, wherein the contrast-induced nephropathy comprises increased serum Cystatin C levels and/or serum creatinine levels compared to a healthy control subject.

10. The method of claim 1, wherein the contrast-induced nephropathy comprises proteinuria and/or increased urinary creatinine levels compared to a healthy control subject.

11. The method of claim 1, wherein the peptide is administered prior to or simultaneous with a radiocontrast dye.