Early marker of proteinuria in patients treated with an Anti-vegf treatment

Inactive Publication Date: 2013-02-07
MAYO FOUND FOR MEDICAL EDUCATION & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes methods and materials for detecting proteinurea in humans who receive anti-VEGF therapy. By identifying patients with proteinuriea, who may develop kidney injury or toxicity as a result of the treatment, appropriate treatment can be initiated. By identifying patients without proteinuriea, unnecessary cessation of anti-VEGF therapy can be avoided. By detecting the presence of urinary podocytes, which indicate proteinuria or a risk for it, this patent provides an effective way to identify patients who may need treatment and avoid unnecessary treatment cessation.

Problems solved by technology

However, a side effect in about 30% of cancer patients receiving anti-VEGF therapy is proteinuria (≧300 mg of total protein in a 24-hour urine sample).
Proteinuria can be associated with characteristic renal pathologic changes of glomerular endotheliosis, leading to renal toxicity.

Method used

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  • Early marker of proteinuria in patients treated with an Anti-vegf treatment

Examples

Experimental program
Comparison scheme
Effect test

example 1

A Case of Podocyturia in a Patient Receiving Anti-VEGF Therapy with Sunitinib

case study

[0034]A 67 year old female presented with a 7.2×6.1 cm mass involving the central and lower portion of the right kidney. Renal function was normal with a creatinine of 1.0 and no proteinuria. She subsequently underwent a right radical nephrectomy and retroperitoneal lymphadenectomy. Pathology confirmed Grade 2, T2, N0, M1 renal cell carcinoma, clear cell type. Sunitinib therapy was initiated, with good response.

[0035]Four months into therapy, renal function worsened with a peak creatinine of 1.5 and 467 mg of protein in 24 hours. Angiotensin receptor blockade with Diovan was initiated. Additional side effects included hypertension, hand and foot syndrome, and drug-induced hypothyroidism.

[0036]After seven months of therapy, her creatinine improved to 1.3 but she remained proteinuric, with a predicted 24 hour protein of 931 mg. At that time, a podocyturia assay was performed as described below and the presence of urinary podocytes was confirmed (FIG. 1).

Detection of Podocytes

[0037]A ...

example 2

Podocyturia in Patients Treated with VEGF Blocking Therapy for Cancer

[0041]The following was performed to determine whether podocyturia is present in patients who, while undergoing anti-VEGF therapy, develop proteinuria (Table 1). In addition, urinary podocyte excretion was compared among patients on anti-VEGF therapy with proteinuria ranging from 101 to 9720 mg / d (Table 1).

Table 1Anti-Type of CancerAge / SexVEGFGFRProteinuriaCells / HPFCholangio68 / FB66420 mg / d0Renal Cell60 / MS / nib39101 mg / d1Colorectal55 / FB1371 + dipstick1Colon66 / FB + S / nib77330 mg / d0GBM59 / FB + S / nib78152 mg / d1Renal Cell73 / MB632144 mg / d>3Renal Cell67 / FSunitib432112 mg / d>3SBC68 / MB596361 mg / d>3GBM70 / MS / nib709720 mg / d>9GBM: glioblastoma multiforme; SBC: small bowel carcinoid; B: bevacizumab; S / nib:sorafenib; HPF: 400x high power field.

[0042]These results demonstrate a higher degree of podocyturia in patients undergoing anti-VEGF therapy with proteinuria in excess of 2 gr / d compared to those treated with the same agents and...

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Abstract

This document provides methods and materials related to determining whether or not a human receiving a therapy (e.g., an anti-VEGF therapy such as a bevacizumab therapy) has developed or is at risk for developing proteinuria. For example, methods and materials for detecting urinary podocytes to determine whether or not a human receiving anti-VEGF therapy has or is at risk for developing proteinuria or kidney injury are provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001]This application claims the benefit of U.S. Provisional Application Ser. No. 61 / 288,514, filed Dec. 21, 2009. The disclosure of the prior application is considered part of (and is incorporated by reference in) the disclosure of this application.BACKGROUND [0002]1. Technical Field[0003]This document relates to methods and materials involved in determining whether or not a human receiving an anti-VEGF therapy has podocyturia (e.g., urinary excretion of podocytes). For example, this document provides methods and materials for detecting the presence or absence of podocytes in a urine sample from a human receiving an anti-VEGF therapy to determine whether or not the human has developed or is at risk for developing proteinuria or kidney injury.[0004]2. Background Information[0005]Angiogenesis has a critical role in the growth, invasion, and metastasis of malignancies. Using angiogenesis inhibitors as an approach to cancer treatment has made si...

Claims

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Application Information

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IPC IPC(8): G01N33/53
CPCG01N33/5091G01N2800/347G01N33/94G01N2800/52G01N2800/50A61K31/404A61K31/44A61K2039/505C07K16/22
Inventor GAROVIC, VESNA D.
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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