Association of CYP3A5 polymorphisms and parathyroid hormone with blood level of tacrolimus in patients with end‐stage renal disease

Abstract

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iPTH is not a significant factor influencing the tacrolimus C/D ratio

“… 2 In a rat model, secondary hyperparathyroidism (SHPT) decreased CYP3A activity, whereas SHPT therapy with cinacalcet restored it. 3 Consistent with this finding, but in contrast to Suzuki et al, 4 a positive correlation between iPTH level and TAC concentration was found in the present study by Tanaka et al 1 and also a study by Hirata et al 5 …”

“…We appreciate our colleagues’ findings on the interesting association between CYP3A5 polymorphism, serum intact‐PTH (iPTH) levels, and tacrolimus (TAC) trough. 1 CYP3A4 and CYPA5 are important determinants of TAC metabolism, which can be described simply by the concentration‐to‐dose (C/D) ratio. 2 In a rat model, secondary hyperparathyroidism (SHPT) decreased CYP3A activity, whereas SHPT therapy with cinacalcet restored it.…”

“…However, the two latter studies included only a few patients (Tanaka et al: 48 patients 1 ; Hirata et al: 12 patient 5 ). Especially for small study groups, data points with extreme values have high leverage in correlation analysis.…”

Response to “iPTH is not a significant factor influencing the tacrolimus C/D ratio”

“…We welcome Westphal et al’s response to our recent publication. As they point out, our 1 and Hirata et al 2 previous retrospective studies have very small sample sizes of 48 and 12 patients, respectively. In our paper, time points of measurements for tacrolimus (TAC) and intact parathyroid hormone (iPTH) were not standardized, and logistic regression analysis did not partition TAC concentration/dose (per body weight) ratio (C/D) into a binary dependent variable.…”

“…In addition, our previous study found that the correlation coefficient of both factors increased from r = 0.305 to 0.428 by excluding these patients. 1 However, kidney transplant recipients take multiple medications for primary and comorbidities, some of which have CYP3A inhibitory activity. Thus, we also consider that iPTH levels may not correlate with TAC C/D in the entire patients who undergo kidney transplantation.…”