Use of Tacrolimus as the Primary Immunosuppression After Renal Transplant in Native Americans and Hispanics

Tacrolimus troughs and genetic determinants of metabolism in kidney transplant recipients: A comparison of four ancestry groups

“…Our findings are supported by a small study that also found no difference between doses required to maintain therapeutic tacrolimus troughs in Native Americans, Hispanics, and non-Hispanic whites. 9 Direct comparisons of our trough and dose data to published work is difficult since targeted concentrations are generally higher than contemporary trough targets, doses are reported in mg/kg, and few studies report dose-normalized troughs, which would allow for direct comparison.…”

“…3 It is well known that tacrolimus troughs and dose requirements vary between recipients of European and African ancestry, African Americans have significantly lower tacrolimus trough concentrations in comparison with European Americans and require higher tacrolimus doses to achieve similar trough concentrations. 9 Cytochromes P450 (CYP) 3A4 and 5 are the main drug metabolizing enzymes for tacrolimus and the genes encoding for these proteins contain important genetic variants. 9 Cytochromes P450 (CYP) 3A4 and 5 are the main drug metabolizing enzymes for tacrolimus and the genes encoding for these proteins contain important genetic variants.…”

“…[4][5][6] Little is known about tacrolimus trough and dose requirements in other populations, although some data suggest that Native American transplant recipients require lower tacrolimus doses possibly due to decreased oral clearance, 7,8 others found that there were no difference between tacrolimus doses between European Americans and Native Americans. 9 Cytochromes P450 (CYP) 3A4 and 5 are the main drug metabolizing enzymes for tacrolimus and the genes encoding for these proteins contain important genetic variants. [10][11][12] These variants differ by ancestry and for some significantly different minor allele frequencies (MAF).…”

Post-Transplant Diabetes Mellitus After Kidney Transplant in Hispanics and Caucasians Treated with Tacrolimus-Based Immunosuppression

“…It has been shown that PTDM significantly increases acute rejection, kidney graft loss, and mortality as well as healthcare costs [ 2 , 3 ]. Several risk factors for PTDM have been reported, including: older age [ 2 , 4 ], obesity[ 5 ], metabolic syndrome [ 6 ], family history of diabetes [ 7 ], prior history of glucose intolerance [ 8 ], African American or Hispanic race/ethnicity [ 9 – 12 ], cytomegalovirus infection [ 13 , 14 ], hepatitis C infection [ 15 ]and the use of calcineurin inhibitors [ 16 , 17 ] and corticosteroids [ 18 – 20 ]. It has been recognized that autosomal dominant polycystic kidney disease [ 21 ] and low serum magnesium levels pre- and post-transplant [ 22 , 23 ] are also risk factors for PTDM.…”

The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring

“…These patients required higher tacrolimus doses to achieve adequate exposures and trough blood levels and were at higher risk for acute rejection and graft loss (13). Other ethnic groups such as the Japanese or Hispanic populations are not different from the Caucasian population because their transplant outcomes were comparable under usual tacrolimus dosages (14, 15), although recently Mancinelli et al. have reported that Latin Americans show reduced tacrolimus absorption compared with W patients (6).…”