Method for the Early Detection of Renal Disease Using Proteomics

Inactive Publication Date: 2007-04-19
CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0022] The nature and advantages of the present invention will be more

Problems solved by technology

It is believed that introduction of therapy early in the disease process will reduce the mortality rate associated with the disease and shorten the time for treatment.
Acute renal failure (ARF) secondary to renal injury, including but not limited to ischemic injury and nephrotoxic injury, remains a common and potentially devastating problem in clinical nephrology.
ARF requiring dialysis also complicates up to 10% of cardiac surgeries in infants and children with congenital heart disease.
ARF persistently continues to result in a high rate of mortality despite significant advances in supportive care.
While these studies have paved the way for successful therapeutic approaches in animal models, translational research efforts in humans have yielded disappointing results, for reasons such as the multifaceted response of the kidney to ischemic injury and a paucity of early markers for ARF with a resultant delay in initiating therapy.
A major reason for the inability to provide preventive and therapeutic measures for ARF in humans is the lack of early biomarkers for ARF.
These indicators are not only insensitive and nonspecific, but also do not allow for early detection of

Method used

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  • Method for the Early Detection of Renal Disease Using Proteomics
  • Method for the Early Detection of Renal Disease Using Proteomics
  • Method for the Early Detection of Renal Disease Using Proteomics

Examples

Experimental program
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Effect test

example 1

[0075] Equal volumes (1μl) of urine were diluted 1:5 with sodium phosphate (pH 6) buffer, and 5 μl was spotted onto an NP20 protein array chip. Each spot was washed with distilled water, and a saturated sinapinic acid solution was used as matrix. The low intensity spectra were obtained with the laser set at an intensity of 145 and the high intensity spectra with the laser set at 195. The resulting spectra were calibrated using All-in-1 peptide / protein standards.

example 2

[0076] To confirm the changes in urinary proteins observed by SELDI-TOF-MS, equal levels of samples were subjected to SDS-PAGE. Briefly, 25 μl urine samples were dissolved in an equal volume of 2X SDS-PAGE loading buffer, boiled for 10 minutes, loaded on a 10-20% Tris-Tricine gel, subjected to electrophoresis, and stained with Coomassie Blue. All values are mean ±SE. SAS version 8.2 was used for statistical analysis of patient characteristics and clinical outcomes. The Mann-Whitney rank sum test was used to compare continuous variables, and Fisher's exact test was used to compare categorical variables.

[0077] Employed Method: The Biomarker Wizard (Ciphergen) was employed for initial clustering and descriptive statistics. Ciphergen Express software was used for hierarchical clustering and to generate Receiver Operating Characteristic (ROC) curves. The area under the curve was calculated to provide a measure of robustness for each biomarker. An area under the curve of 0.5 is considere...

example 3

[0078] The primary outcome of acute renal injury, defined as a 50% or greater increase in serum creatinine from baseline, occurred in 15 of 60 consecutive patients, yielding an incidence rate of 25%. Out of these, 5 patients displayed an increase in serum creatinine in the 24-48 hours after CPB, but in the other 10 patients the increase was further delayed to the 48-72 hour period after CPB. Thus, the diagnosis of acute renal injury using currently accepted clinical practices could be made only days after the inciting event. Based on the primary outcome, patients were classified into “control” and acute renal injury or “ARF” groups.

[0079] Comparisons were made between the ARF group (n=15) and age- and gender-matched controls (n=15). There were no significant differences between the two groups in ethnic origin, hourly urine output, urine creatinine, or urine specific gravity measurements at baseline. Patients in the ARF group encountered longer cardiopulmonary bypass times compared ...

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Abstract

A method for the detection of an early biomarker for assessing a change in renal status in a mammalian subject following a renal event. The method typically includes the steps of (a) providing a body fluid sample obtained from a mammalian subject; (b) analyzing the molecular weight of the proteins in the sample using proteome analysis; and (c) identifying the presence of a protein in the sample selected from the group consisting of a 6.4 kDa protein, a 28.5 kDa protein, a 33 kDa protein, a 44 kDa protein, a 67 kDa protein, and combinations thereof. The presence of one of these proteins can serve as an early biomarker for assessing a change in renal status. The levels of these proteins can be compared to predetermined levels, and thus provide a determination of the subject's renal status. The invention also includes a method of assessing the administration of aprotinin during cardio-pulmonary bypass surgery and provides for methods where the level of the 6.4 kDa biomarker in the subject's urine directs a caregiver's therapeutic decision regarding the intra-operative administration of aprotinin.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of U.S. Provisional Application No. 60 / 673,453, filed on Apr. 21, 2005.FIELD OF THE INVENTION [0002] The present invention relates generally to a method of determining the renal status of a subject, and in particular to a method of determining early impaired renal status and nephrotoxicity in a subject. BACKGROUND OF THE INVENTION [0003] Early detection of disease states in mammals has been the focus of much recent research. For disease detection, the public-health community has historically relied on laboratory tests that can sometimes take days or even weeks to return a result. The increased availability of better and faster diagnostic tests, however, promises the possibility of more automated and earlier disease detection and subsequent intervention. It is believed that introduction of therapy early in the disease process will reduce the mortality rate associated with the disease and shorten the tim...

Claims

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Application Information

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IPC IPC(8): G01N33/53
CPCG01N33/6842G01N33/6848G01N33/6851G01N2800/226G01N2800/347G01N33/6893G01N2570/00G01N2800/32G01N2800/52
Inventor DEVARAJAN, PRASAD
Owner CHILDRENS HOSPITAL MEDICAL CENT CINCINNATI
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