Overview of Antibiotic-Induced Nephrotoxicity.

Drug-induced nephrotoxicity accounts for up to 60% of cases of acute kidney injury (AKI) in hospitalized patients and is associated with increased morbidity and mortality in both adults and children. Antibiotics are one of the most common causes of drug-induced nephrotoxicity. Mechanisms of antibiotic-induced nephrotoxicity include glomerular injury, tubular injury or dysfunction, distal tubular obstruction from casts, and acute interstitial nephritis (AIN) mediated by a type IV (delayed-type) hypersensitivity response. Clinical manifestations of antibiotic-induced nephrotoxicity include acute tubular necrosis (ATN), AIN, and Fanconi syndrome. Given the potential nephrotoxic effects of antibiotics on critically ill patients, the use of novel biomarkers can provide information to optimize dosing and duration of treatment and can help prevent nephrotoxicity when traditional markers, such as creatinine, are unreliable. Use of novel kidney specific biomarkers, such as cystatin C and urinary kidney injury molecule-1 (KIM-1), may result in earlier detection of AKI, dose adjustment, or discontinuation of antibiotic and development of nonnephrotoxic antibiotics.

The Immune System and Idiopathic Nephrotic Syndrome.

Idiopathic nephrotic syndrome often responds to immunosuppressive treatment. Nevertheless, this syndrome-and the drugs used to treat it-remain important causes of patient morbidity. Idiopathic nephrotic syndrome is usually caused by minimal change disease or FSGS, diseases that primarily affect the podocytes. In spite of decades of research, the underlying causes of both diseases remain incompletely understood. There is, however, a large body of observational and experimental data linking the immune system with both minimal change disease and FSGS, including associations with systemic infections and hematologic malignancies. Perhaps most compellingly, many different immunomodulatory drugs are effective for treating idiopathic nephrotic syndrome, including biologic agents that have well-defined immune targets. In fact, the unexpected efficacy of targeted therapeutic agents has provided important new insights into the pathogenesis of these diseases. Given the large number of drugs that are available to deplete or block specific cells and molecules within the immune system, a better understanding of the immunologic causes of idiopathic nephrotic syndrome may lead to better diagnostic and therapeutic approaches.