The first manifestation of disease is typically a sharp increase in serum creatinine concentration on routine laboratory examination. Recent exposure to a known nephrotoxin strongly suggests the diagnosis of ATN, whereas hemodynamic compromise may cause either prerenal state or ATN. Thus distinguishing between prerenal state and ATN is often an important part of the differential diagnosis. As described in the overview of AKI, the distinction between prerenal and intrarenal disease can often be established based on the response to an intravenous fluid bolus, as well as laboratory markers such as FENa and the BUN : creatinine ratio. Microscopic analysis of urine may also facilitate the diagnosis. In the prerenal state, urine either appears normal or contains hyaline casts, which form when Tamm-Horsfall protein, secreted in the distal tubule, becomes concentrated and aggregates. In contrast, ATN often features “muddy-brown” granular casts or epithelial casts.