The serum creatinine continued to improve to a level of 1.23 mg/dL at week 6 of treatment. Discussion Atypical HUS (aHUS) is a rare disease of uncontrolled complement merely activation associated with high mortality and progression to end stage renal disease (6). It may be caused by genetic mutations (7), ADAMTS-13 deficiency, HIV, malignancy, #e-book randurls[1|1|,|CHEM1|]# Inhibitors,research,lifescience,medical pregnancy, autoimmune diseases and drugs (8). Typically, GiHUS is dose related with median cumulative dose reported to be 22 g/m2

(range, 4-81 g/m2) given over 7.5 months (range, 2-34 months) (9). In the four cases we report, the median cumulative gemcitabine dose was 21.2 g/m2. Other chemotherapeutic agents, have been implicated in causing thrombotic microangiopathy Inhibitors,research,lifescience,medical such as mitomycin C, cisplatin, carboplatin and bevacizumab (10,11). Of our four patients, two

had received carboplatin, one had received cisplatin and one had received bevacizumab in past treatment regimens. The pathophysiology of GiHUS is not well understood. In other forms of aHUS, it Inhibitors,research,lifescience,medical appears that there is uncontrolled proximal alternative pathway complement activation that leads to increased terminal membrane attack complex causing endothelial cell activation (6). There is evidence of activation of monocytes, neutrophils, and platelet activation and aggregation. Gemcitabine may directly damage Inhibitors,research,lifescience,medical endothelial cells, resulting in platelet aggregation and intravascular hemolysis. The typical features of HUS may not always be seen in GiHUS. All patients were anemic but had varying degrees of thrombocytopenia. Rare or no schistocytes were identified on the peripheral smear of three individuals. The renal function changes occurred in a subacute fashion in all of these patients. Because of the lack of typical characteristics features of HUS, diagnosis was delayed. Three of four patients had subtle elevation of serum creatinine 2-6 months Inhibitors,research,lifescience,medical before suspecting HUS. Gemcitabine was stopped as it was suggested

that 56% of these cases resolve with simply stopping the offending drug (12). Unfortunately, none of our patients showed improvement of renal function or hemolysis even after stopping gemcitabine for 3-5 weeks and eculizimab was initiated upon lack of clinically significant improvement even with other therapies such as corticosteroids. Eculizimab is Dacomitinib a recombinant humanized monoclonal antibody that binds to complement C5 protein, inhibiting its cleavage, and thus preventing the generation of the terminal complement attack complex C5b-9 (13). It was initially approved for treating paroxysmal nocturnal hemoglobinuria in 2004 (14). It was first used in a case of atypical HUS in 2009 treated with a single dose leading to 8 months of stable renal function and without hemolysis (15).