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Application of Liquid Chromatography–Mass Spectrometry Technology for Early Detection of Microalbuminuria in Patients with Kidney Disease

(Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota;

^aaddress correspondence to this author at: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55901; fax 507-284-9758; e-mail singh.ravinder@mayo.edu)

The first 300 words of the full text of this article appear below.

Proteinuria is an early and sensitive marker of renal damage in many forms of chronic kidney disease. In diabetes mellitus, mild albuminuria occurs early in the course of renal damage, and this microalbuminuria, defined as urinary albumin excretion of 30–300 mg/day (20–200 µg/min), is the best noninvasive predictor of subsequent clinical diabetic nephropathy. Without proper treatment, early diabetic kidney damage progresses to end-stage kidney failure in 5–7 years. With early detection, however, the onset of kidney disease can be slowed, halted, and in some cases reversed through treatment with drugs such as inhibitors of angiotensin-converting enzyme and blockers of angiotensin-2 receptor, particularly if drug treatments is combined with tight blood sugar control and, possibly, decreased protein intake (1)(2). Therefore, strong interest is directed toward detecting patients at risk of diabetic nephropathy as early as possible (3).

Current microalbuminuria assays use various immunochemical methods (4). These assays may lead to underestimation of albuminuria in some patients, possibly contributing to delayed diagnosis of early diabetic nephropathy, as indicated by data generated with a recently developed, FDA-cleared size-exclusion HPLC with ultraviolet detection (SEC-HPLC-UV) method (Accumin^TM, AusAm Biotechnologies). Urine sample analysis with this assay has yielded consistently higher albumin concentrations than immunoassays (5). In one study, microalbuminuria was detected by SEC-HPLC-UV in 53% of urine samples from diabetic patients that were normalbuminic according to an immunochemical method (6). In another study, the SEC-HPLC-UV method was reported to detect microalbuminuria 1–12 years earlier than widely used commercial tests (7). It has been hypothesized that the higher values obtained with the SEC-HPLC-UV assay are attributable to detection of modified forms of albumin. These redox and glycation modifications of the albumin do not change the size of the albumin markedly, and . . . [Full Text of this Article]

The following articles in journals at HighWire Press have cited this article:

				D. Sviridov, S. K. Drake, and G. L. Hortin Reactivity of Urinary Albumin (Microalbumin) Assays with Fragmented or Modified Albumin Clin. Chem., January 1, 2008; 54(1): 61 - 68. [Abstract] [Full Text] [PDF]

				G. L. Hortin A New Era in Protein Quantification in Clinical Laboratories: Application of Liquid Chromatography-Tandem Mass Spectrometry Clin. Chem., April 1, 2007; 53(4): 543 - 544. [Full Text] [PDF]

				R. Singh, F. W. Crow, N. Babic, W. H. Lutz, J. C. Lieske, T. S. Larson, and R. Kumar A Liquid Chromatography-Mass Spectrometry Method for the Quantification of Urinary Albumin using a Novel 15N-Isotopically Labeled Albumin Internal Standard Clin. Chem., March 1, 2007; 53(3): 540 - 542. [Full Text] [PDF]