Factors Affecting Circulating mRNA for Nephrin

Abstract

Kidney disease affects more than 20 million individuals in the United States alone. Although the causes of kidney failure are diverse, the glomerular filtration barrier is often the target of injury. Identification of the type of disease is important for targeting therapy. One area of particular interest is the ability to predict which patients with nephrotic syndrome might respond to steroids or cytotoxic therapies and which will not (1). Often this depends on renal biopsy, an invasive procedure with some risk of complications. A noninvasive test to determine the type of renal disease would be advantageous. During the past decade, nucleic acids have been detected in the circulation, and measurements of tissue-specific DNA and mRNA offer enormous potential for diagnosis and prognosis (2). Increased amounts of nucleic acids have been reported in disease, including lung cancer (3), thyroid cancer (4)(5), stroke(6), and trauma (7). We have recently shown that measurement of total DNA in plasma is a good prognostic marker of outcome in critically ill patients (8). In another study we observed that mRNA for rhodopsin is increased in diabetic retinopathy, and it may be a useful and inexpensive way to detect and monitor diabetic patients for retinopathy (9). Nephrin, a transmembrane protein with a large extracellular portion including 8 immunoglobulin-like domains, is expressed by visceral epithelial cells (podocytes) in the slit diaphragm of the glomerulus (10). A product of the NPHS1 gene located on chromosome 19, this protein is crucial for the integrity of the slit diaphragm, and abnormalities in this protein can lead to proteinuria and …