Tacrolimus-Induced Neutropenia in Renal Transplant Recipients

Abstract

SummaryTacrolimus has become an important cornerstone in the prevention of rejection after kidney transplantation. However, its use has been complicated by several side effects, including chronic allograft nephropathy, diabetes mellitus, arterial hypertension, and neurotoxicity. Tacrolimus-induced neutropenia is a less recognized, but potentially harmful complication. Three patients with severe neutropenia developing within 3 months after kidney transplantation are described. After having excluded other well known causes, tacrolimus was considered the most probable culprit. Definitive proof of this hypothesis was obtained by discontinuation of tacrolimus and switching to cyclosporine, which led to recovery of white blood cell count in all three patients.

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“…Persistent leukopenia was managed by extra doses of G-CSF, reduction of MMF dose, valganciclovir, trimethoprim/sulfamethoxazole, and other offending drugs that contribute to leukopenia and can be stopped temporarily. 27,28 Details of patients who developed CMV disease or rejection episodes during the study period were recorded. Associated infections were also recorded if they necessitated hospital admission.…”

“…Tacrolimus can cause more leukopenia than cyclosporine. 27,28 However, fewer patients had received tacrolimus in group 2 (P < .05), which had more leukopenia attacks. In addition, the greater numbers of patients in group 2 with cyclosporine treatment may have caused less exposure to mycophenolic acid than the tacrolimus-MMF combination in group 1.…”

“…5,6 Half of our patients received thymoglobulin (Table 1), which has a severe bone marrow suppressive effect. 27,28 Because thymoglobulin treatment was equal in both groups, we looked for other causes for the high incidence of leukopenia in group 2. Tacrolimus can cause more leukopenia than cyclosporine.…”

Replacement of Mycophenolate Acid With Everolimus in Patients Who Became Neutropenic After Renal Transplant

“…Less commonly, antithymocyte globulin, alemtuzumab, rituximab, tacrolimus (TAC), cyclosporine, sirolimus, cotrimoxazole, omeprazole, and angiotensinconverting enzyme inhibitors have been reported to cause neutropenia. [4][5][6][7][8][9][10][11] The contribution of these agents is difficult to assess because they are frequently used in combinations. Remission of neutropenia after drug elimination or discontinuation can be used as indirect evidence.…”

Polimorfismos em genes envolvidos na farmacodinâmica de tacrolimo e everolimo e sua relação com a resposta ao tratamento imunossupressor, em receptores de transplante renal

“…Uso de inibidores de calcineurina ou mTOR também foi associado com aumento de episódios de leucopenia (DE RYCKE et al, 2011).…”