Figure 2.

Mechanisms of antimicrobial-induced nephrotoxicity. (a) ATN: begins with endocytosis of drug from the urine into tubular epithelial cells (a1). Once inside the cell, the drug causes damage to cell organelles (a2). This initiates the process of cellular apoptosis and death, and release of systemic inflammatory signals (a3). Renal blood flow is then reduced (a4) as a result of tubuloglomerular feedback mechanisms. (b) AIN: antigen from either freely filtered drug or drug that is circulating in the blood is deposited on the basement membrane (b1). The antigen is recognized by dendritic cells (b2), which induce a T cell-mediated immune response (b3) and interstitial inflammation with pyuria (b4). (c) Crystal (obstructive) nephropathy: drug is filtered into the urine (c1). When the urine becomes supersaturated with drug, as in the setting of decreased urine flow, the drug precipitates (often as crystals) and obstructs the tubular lumen (c2). This leads to the release of inflammatory signals into the blood (c3), as well as induction of cellular apoptosis and reduced renal blood flow via tubuloglomerular feedback mechanisms (c4).