Effects of CYP3A5 polymorphism and the tacrolimus 12 h concentration on tacrolimus-induced acute renal dysfunction in patients with lupus nephritis

Abstract

1. The purpose of the present study was to investigate the effect of tacrolimus concentration in blood 12 h after administration (C_12h) on acute renal dysfunction in patients with lupus nephritis (LN) taking tacrolimus once daily.

2. Five of the 35 LN patients experienced tacrolimus-induced acute renal dysfunction.

3. The average annual C_12h of tacrolimus was higher for patients with events of elevated serum creatinine level than for patients not experiencing these events [6.4 (5.6–8.8) versus 2.8 (2.2–4.6) ng/mL, respectively, p = 0.001].

4. The average annual tacrolimus C_12h was higher for patients with CYP3A5*3/*3 (PM) than for patients with the CYP3A5*1 allele (EM) [4.6 (3.2–6.6) versus 2.5 (2.0–3.1) ng/mL, respectively, p = 0.002].

5. The area under the receiver operating characteristic was 0.887, which gave the best sensitivity (80.0%) and specificity (86.7%) at a tacrolimus C_12h (average annual C_12h or C_12h at events) threshold of 5.2 ng/mL.

6. C_12h measurements, CYP3A5 genotyping and dose adjustments of tacrolimus should be performed to prevent acute renal dysfunction in LN patients taking tacrolimus once daily.

• Acute renal dysfunction
• CYP3A5 polymorphism
• lupus nephritis
• tacrolimus
• therapeutic drug monitoring

Declaration of interest

This work was supported by a grant (No. 20722276) from the Japan Society for the Promotion of Science, Tokyo, Japan.

The authors declare no conflict of interest associated with this manuscript.