Sex differences in transplantation

Abstract

Sex plays a role in the incidence and progression of a wide variety of diseases and conditions related to transplantation. Additionally, a growing body of clinical and experimental evidence suggests that sex can impact the pharmacokinetics and pharmacodynamics of several commonly used immunosuppressive and anti-infective drugs in transplant recipients. A better understanding of these sex differences will facilitate advances in individualizing treatment for patients and improve outcomes of solid organ transplantation. Here, we provide a review of sex-related differences in transplantation and highlight opportunities for future research directions.

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

“…36 In transplantation, several complications are associated with sex, including acute rejection, graft loss and viral (re)activations. 11,13,37,38 However, the underlying reasons for these sex differences are not well understood; possible causes include the hormonal regulation of the immune system, the effects of pregnancy, and differences in the metabolism of drugs routinely employed in transplantation. 11 For example, there is tentative evidence of sexrelated differences in the pharmacokinetics of (val)ganciclovir.…”

“…11,13,37,38 However, the underlying reasons for these sex differences are not well understood; possible causes include the hormonal regulation of the immune system, the effects of pregnancy, and differences in the metabolism of drugs routinely employed in transplantation. 11 For example, there is tentative evidence of sexrelated differences in the pharmacokinetics of (val)ganciclovir. 11,12 Thus, ganciclovir clearance has been observed to be 24% faster in female transplantation patients, suggesting higher activity of the organic anion transporter 1.…”

“…11 For example, there is tentative evidence of sexrelated differences in the pharmacokinetics of (val)ganciclovir. 11,12 Thus, ganciclovir clearance has been observed to be 24% faster in female transplantation patients, suggesting higher activity of the organic anion transporter 1. 11,12 Furthermore, it has been shown repeatedly that women and men have different anti-CMV immunological profiles, with an impact in the graft function and even the phenotype of the immune system as a whole.…”

“…Interestingly, there is evidence of sex differences in both ganciclovir pharmacokinetics and the anti-CMV immune response. [11][12][13][14][15][16][17][18] Thus, female patients have been shown to have a faster ganciclovir clearance, and distinct anti-CMV immunological profiles e.g. higher number of secreting anti-CMV T cells.…”

“…higher number of secreting anti-CMV T cells. [11][12][13][14]18 In spite of this, there are to our knowledge still no studies on the influence of sex on the clinical outcomes of CMV prevention strategies. In this work, we provide evidence that prophylaxis might be associated with inferior transplantation outcomes in female patients.…”