J Korean Med Sci.  2020 Jun;35(24):e185. /10.3346/jkms.2020.35.e185.

Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients

• Jung HY
• Lee S
• Jeon Y
• Choi JY
• Cho JH
• Park SH
• Kim YL
• Kim HK
• Huh S
• Won DI
• Kim CD

• KMID: 2503013
• DOI: http://doi.org//10.3346/jkms.2020.35.e185

Abstract

Background
Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C0) and dose with renal transplant outcomes and adverse events.
Methods
This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C0 of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections.
Results
No differences in MPA C0 and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C0 was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C0 ≥ 3.5 μg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24–11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27–27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15–12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR.
Conclusion
Either a higher MPA C0 or dose is associated with an increased risk of cytopenia, but neither a lower MPA C0 nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.

Keyword

Mycophenolic Acid; Kidney Transplantation; Drug Monitoring; Dose; Graft Rejection

Figure

• 

  Fig. 1 Correlations between MPA C0 and MPA dose. MPA C0 was correlated with (A) daily MMF dose (R2 = 0.083, β = 0.002, P < 0.001) and (B) EC-daily MPS dose (R2 = 0.020, β = 0.001, P = 0.008).MPA = mycophenolic acid, C0 = trough concentration, MMF = mycophenolate mofetil, EC-MPS = enteric-coated mycophenolate sodium.

• 

  Fig. 2 Correlations between MPA C0 and TAC C0. MPA C0 was correlated with TAC C0 (R2 = 0.017, P < 0.001).MPA = mycophenolic acid, C0 = trough concentration, TAC = tacrolimus.

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