IP Library Granted Patent US 11,965,896
Granted Patent B2
US 11,965,896 · App. 17/873,968 · Granted Apr 23, 2024

Methods of treating patients at risk for renal injury and renal failure

Inventors: Richard A. Zager (Seattle, WA); Donald Jeffrey Keyser (Southlake, TX); Alvaro F. Guillem (Lantana, TX)
Assignee: Renibus Therapeutics, Inc.
G01N33/6893A61K31/277A61K31/409A61K33/26G01N2800/347
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Quick Facts
Patent No.
US 11,965,896
App. No.
17/873,968
Granted
Apr 23, 2024
Kind
B2
Abstract

The p21 biomarker is utilized in the evaluation of whether a patient is suffering from kidney injury or failure, and can be used in methods of treating kidney injury or failure by determining the appropriateness of 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.

Claims (14)

1. A method of treating a patient at risk for having suffered kidney injury or kidney disease progression comprising:

(a) performing an assay to determine the level of cyclin-dependent kinase inhibitor p21 in the patient; and

(b) if the patient exhibits an elevated level of the cyclin-dependent kinase inhibitor p21, treating the patient to reduce the risk of further kidney injury, wherein the treatment comprises one or more of administration of one or more steroids, ACE inhibitors, nuclear factor erythroid 2-related factor 2 (NRF2) activators, Angiotensin II receptor blockers, antioxidants, aldosterone antagonists, anti-inflammatory, anti-fibrotic, vasopressin antagonists, Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors, immunosuppressive agents, organ protection with a combination of iron or iron sucrose and a heme protein degradation inhibitor, or acute kidney injury treatments, or 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, wherein the cyclin-dependent kinase inhibitor p21 is of SEQ ID NO. 1, wherein (a) performing an assay to determine the level of p21 in the patient, also comprises performing an assay to determine the level of microalbumin, ferritin, hemopexin, and haptoglobin in the patient.

2. A method of treating a patient determined to be at risk for future kidney injury comprising:

(a) performing an assay to determine the level of the cyclin-dependent kinase inhibitor p21 in the patient;

(b) performing an assay to determine the level of urinary albumin in the patient; and

(c) if the patient exhibits elevated levels of the cyclin-dependent kinase inhibitor p21 and albumin, treating the patient to reduce the risk of further kidney injury, wherein the treatment comprises one or more of administration of one or more steroids, ACE inhibitors, NRF2 activators, antioxidants, aldosterone antagonists, anti-inflammatory, anti-fibrotic, vasopressin antagonists, SGLT-2 inhibitors, immunosuppressive agents, organ protection with a combination of iron or iron sucrose and a heme protein degradation inhibitor, or acute kidney injury treatments, or 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, wherein the cyclin-dependent kinase inhibitor p21 is of SEQ ID NO. 1, wherein (a) performing an assay to determine the level of p21 in the patient, also comprises performing an assay to determine the level of microalbumin, ferritin, hemopexin, and haptoglobin in the patient.

3. A method of treating a patient at risk for having suffered kidney injury or kidney disease progression comprising:

(a) performing an assay to determine the level of cyclin-dependent kinase inhibitor p21 in the patient; and

(b) if the patient exhibits an elevated level of the cyclin-dependent kinase inhibitor p21, treating the patient to reduce the risk of further kidney injury, wherein the treatment comprises one or more of administration of one or more steroids, ACE inhibitors, nuclear factor erythroid 2-related factor 2 (NRF2) activators, Angiotensin II receptor blockers, antioxidants, aldosterone antagonists, anti-inflammatory, anti-fibrotic, vasopressin antagonists, Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors, immunosuppressive agents, organ protection with a combination of iron or iron sucrose and a heme protein degradation inhibitor, or acute kidney injury treatments, or 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, wherein the cyclin-dependent kinase inhibitor p21 is of SEQ ID NO. 1, wherein the patient has undergone a kidney transplant.

4. A method of treating a patient determined to be at risk for future kidney injury comprising:

(a) performing an assay to determine the level of the cyclin-dependent kinase inhibitor p21 in the patient;

(b) performing an assay to determine the level of urinary albumin in the patient; and

(c) if the patient exhibits elevated levels of the cyclin-dependent kinase inhibitor p21 and albumin, treating the patient to reduce the risk of further kidney injury, wherein the treatment comprises one or more of administration of one or more steroids, ACE inhibitors, NRF2 activators, antioxidants, aldosterone antagonists, anti-inflammatory, anti-fibrotic, vasopressin antagonists, SGLT-2 inhibitors, immunosuppressive agents, organ protection with a combination of iron or iron sucrose and a heme protein degradation inhibitor, or acute kidney injury treatments, or 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, wherein the cyclin-dependent kinase inhibitor p21 is of SEQ ID NO. 1, wherein the patient has undergone a kidney transplant.

Assignments (2)
SECURITY INTEREST Recorded Jun 4, 2026
From: RENIBUS THERAPEUTICS, INC.
To: AVENUE VENTURE OPPORTUNITIES FUND II, L.P.
Reel/Frame 074858/0020 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 26, 2022
From: ZAGER, RICHARD A.; KEYSER, DONALD JEFFREY; GUILLEM, ALVARO F.
To: RENIBUS THERAPEUTICS, INC.
Reel/Frame 060628/0809 →
Continuity (4)
Continuation 16422156 · May 24, 2019
Provisional Application 62715508 · Aug 7, 2018
Provisional Application 62676157 · May 24, 2018
Related Publication 20230314448A1 · Oct 5, 2023