Rhabdomyolysis-related Renal Tubular Damage Studied by Proton Nuclear Magnetic Resonance Spectroscopy of Urine

Abstract

Rhabdomyolysis is a common clinical and laboratory syndrome, resulting from skeletal muscle injury, that leads to the release of potentially toxic muscle cell contents, specifically myoglobin, into the plasma (1)(2). Rhabdomyolysis can be induced by many different mechanisms and has been implicated as a major cause of acute renal failure. However, when correct treatment is provided, it is usually reversible. Acute tubular necrosis after rhabdomyolysis does not always appear to parallel the degree of muscle damage, but it may be related to other factors that potentiate the effects of myoglobinuria, such as hypotension, acidosis, and volume depletion. The pathophysiology of the renal injury is not fully understood, but it probably includes a combination of hypoperfusion/ischemia, iron tubular cytotoxicity, and cast formation potentially leading to proximal tubular necrosis and acute renal failure. The combination of fibrates plus 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) is an effective and generally well-tolerated treatment for high-risk patients with mixed dyslipidemias, and side effects, mainly hepatic and muscular disorders, are rare. However, when they do occur, muscular damage may be severe, leading to rhabdomyolysis (3)(4). High-resolution proton nuclear magnetic resonance (1H-NMR) spectroscopy is a nondestructive and noninvasive technique that can provide complete structural analysis of a wide range of organic molecules in complex mixtures. NMR spectroscopy has been used for the detection of low-molecular-weight metabolites present in biological fluids as a result of changes in physiologic status, toxic insult, or disease processes (5). NMR provides quantitative information on the low-molecular-weight metabolites present in the specimen studied and allows the detection of unexpected constituents related to disease or tissue damage. Urinalysis by NMR spectroscopy has led to detailed investigation of the excretion pattern in various physiologic and pathologic situations, such as inborn errors of metabolism, organ transplantation, and renal damage produced by acute …