Cholesterol embolization syndrome (CES) induced by thrombolytic therapy is a rare syndrome with a high incidence of morbidity and mortality. The variability in clinical presentations may cause a delay in diagnosis of CES. This article presents a comprehensive review of the English literature from January 1980 to December 2007 identifying all published case reports of CES induced by thrombolytic therapy. Multiple electronic databases were searched and relevant reference lists were hand searched to identify all case reports. Thirty cases of thrombolytic-induced CES were identified. Indications for thrombolysis were acute myocardial infarction (28 patients) and deep venous thrombosis (two patients). Skin and renal involvement were the most common presentations. Skin manifestations included livedo reticularis, rash, and skin mottling. Other clinical symptoms included cyanotic toes, gastrointestinal bleeding, or perforation, myalgias, retinal emboli, and CNS involvement. Morbidity and mortality were high. Outcomes included chronic hemodialysis in eight patients, four patients underwent amputations, seven patients developed or had progression of their chronic kidney disease, and seven deaths occurred.CES presents as multiorgan dysfunction and should be considered in the differential diagnosis of the symptom complex that may develop after thrombolytic therapy. Diagnosis of CES can be difficult as a result of the variable clinical presentations. A thorough clinical history and physical examination are essential first steps in establishing a diagnosis. Confirmatory diagnosis requires biopsy of the target organs. Measures to reduce the likelihood of recurrence should be taken and include avoidance of anticoagulation therapy and vascular procedures. Unfortunately, therapy remains supportive and the outcome is invariably poor.

Renal drug interactions can result from competitive inhibition between drugs that undergo extensive renal tubular secretion by transporters such as P-glycoprotein (P-gp). The purpose of this study was to evaluate the effect of itraconazole, a known P-gp inhibitor, on the renal tubular secretion of cimetidine in healthy volunteers who received intravenous cimetidine alone and following 3 days of oral itraconazole (400 mg/day) administration. Glomerular filtration rate (GFR) was measured continuously during each study visit using iothalamate clearance. Iothalamate, cimetidine, and itraconazole concentrations in plasma and urine were determined using high-performance liquid chromatography/ultraviolet (HPLC/UV) methods. Renal tubular secretion (CL(sec)) of cimetidine was calculated as the difference between renal clearance (CL(r)) and GFR (CL(ioth)) on days 1 and 5. Cimetidine pharmacokinetic estimates were obtained for total clearance (CL(T)), volume of distribution (Vd), elimination rate constant (K(el)), area under the plasma concentration-time curve (AUC(0-240 min)), and average plasma concentration (Cp(ave)) before and after itraconazole administration. Plasma itraconazole concentrations following oral dosing ranged from 0.41 to 0.92 microg/mL. The cimetidine AUC(0-240 min) increased by 25% (p < 0.01) following itraconazole administration. The GFR and Vd remained unchanged, but significant reductions in CL(T) (655 vs. 486 mL/min, p < 0.001) and CL(sec) (410 vs. 311 mL/min, p = 0.001) were observed. The increased systemic exposure of cimetidine during coadministration with itraconazole was likely due to inhibition of P-gp-mediated renal tubular secretion. Further evaluation of renal P-gp-modulating drugs such as itraconazole that may alter the renal excretion of coadministered drugs is warranted.

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Despite the commonly accepted indications for hemodialysis and extracorporeal depuritive techniques, some clinicians have come to rely on blood purification for clinical states where the targeted substance for removal differs from uremic waste products. Over the last decade, a number of studies have emerged to help define the application of extracorporeal blood purification (ECBP) to these "nonuremic" indications. This review describes the application of extracorporeal blood purification in clinical states including sepsis, rhabdomyolysis, congestive heart failure, hepatic failure, tumor lysis syndrome, adult respiratory distress syndrome, intravenous contrast exposure, and lactic acidosis. Additional comments are provided to review existing literature on thermoregulation and osmoregulation, including acute brain injury.