Method for the Early Detection of Renal Disease Using Proteomics

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...

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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 the disease.

In current clinical practice, ARF is typically diagnosed by measuring a rise in serum creatinine over time, which is an unreliable indicator for measuring acute changes in kidney function.

Currently there are no tools available for the early diagnosis of impaired renal status.

The lack of early biomarkers for acute renal injury thus has severely slowed progress in finding effective therapies within the narrow window of opportunity.

Despite considerable effort directed at early detection of ARF, no cost-effective screening tests have been developed to date.

Although two-dimensional gel electrophoresis is one of the most powerful methods in the current study of proteomics, this method is labor-intensive, time consuming, and limited in sensitivity.

The two-dimensional gel electrophoresis method also suffers from poor reproducibility.

However, until now, no early stage molecular markers have been identified for ARF.

Several tubular proteins have been measured in the urine, with conflicting and unsatisfactory results.

There is currently a lack of a reliable biomarker for the early determination of renal injury and disease caused by ischemia and / or nephrotoxicity.

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