Method for kidney disease detection by protein profiling

Abstract

The invention provides a method of generating and analysing a urinary protein fragmentation profile, in terms of the size, and sequence of particular fragments derived from intact filtered proteins together with the position where enzymes scission occurs along the protein polypeptide chain is characteristic of the diseased state of the kidney. With the recognition that filtered proteins are degraded during renal passage, the methods described in this application will be able to detect protein fragments derived from proteins generated by non-renal disease. The urinary analysis of these filtered proteins would currently not detect the intact form of these proteins. Therefore, a method as described to detect and analyse fragments resulting from degradation during renal passage that will be able to detect the seriousness of the disease.

Description

[0001] Related application reference

[0002] This application claims priority to US Provisional Application 60 / 301,251, filed June 28,2001. field of invention

[0003] The present invention relates to an improved method of detecting early stage renal disease and / or renal complications of the disease, especially diabetic complications. Background of the invention

[0004] Excessive protein, such as albumin, in the urine indicates kidney disease. Diabetic nephropathy is one such disease.

[0005] Applicants have discovered that proteins, including albumin, are normally secreted as a mixture of native proteins and fragments that are specifically produced during renal passage (Osicka T.M et al., Nephrology, 2:199-212( 1996)). During renal passage, proteins are severely degraded by the posterior glomerulus (basement membrane) including tubular cells. Lysosomes in tubular cells are responsible for degrading proteins secreted during renal passage. Figure 1 shows the progressi...

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