Hemolytic-uremic syndrome tacrolimus nephrotox

Tacrolimus acute nephrotoxicity can manifest itself as clinically significant acute renal failure, asymptomatic changes in glomerular filtration rate [254,527-533] or hemolytic-uremic syndrome [534-538]. Even being a cause of hemolytic-uremic syndrome, tacrolimus has been advocated as an alternative treatment for patients with CsA-induced hemolytic-uremic syndrome [539, 540]. However, cases of patients with CsA-induced hemolytic-uremic syndrome that recurred after conversion from CsA to tacrolimus have been reported, indicating that this approach is not completely safe [541]. 

Toxicities of the PSIs can include profound myelosuppression (especially thrombocytopenia), hepatotoxicity, diarrhea, hypertriglyceridemia, pneumonitis, and headache. Because nephrotoxicity is of major concern when administering calcineurin inhibitors, there is interest in increased early use of PSIs since renal toxicity is less common with these agents. However, increased use in stem cell transplantation regimens as graft-versus-host disease prophylaxis, particularly when combined with tacrolimus, has revealed an increased incidence of hemolytic-uremic syndrome. 

In 16 renal transplant patients with suspected ciclosporin nephrotoxicity, the addition of mycophenolate allowed safe reduction in the dosage of ciclosporin, with subsequent improvement in renal function and arterial blood pressure over 6 months (1). It might allow the rapid withdrawal of glucocorticoids in patients taking ciclosporin or tacrolimus, and therefore reduce the incidence of glucocorticoid-induced post-transplant diabetes, hypercholesterolemia, and hypertension (2). There have been several reports of patients with ciclosporin-associated thrombotic micro-angiopathy/hemolytic-uremic syndrome in whom mycophenolate was successfully substituted (3,4). 

The nephrotoxicity profile of tacrolimus is very similar to that of CsA. Tacrolimus induces acute and reversible functional changes in renal function, chronic renal irreversible structural injury, electrolyte disturbances, renal tubular acidosis and hemolytic-uremic syndrome. There are some few and important differences tacrolimus induces less hypertension but more glucose metabohsm impairment than CsA [242, 515-521]. Also resembling CsA, tacrolimus association with drugs that interfere with the cytochrome P-450 metabolism or with other nephrotoxic drugs, can precipitate acute renal dysfunction [522-526]. ... 

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