Copyright ©The Author(s) 2023.
World J Transplant. Sep 18, 2023; 13(5): 254-263
Published online Sep 18, 2023. doi: 10.5500/wjt.v13.i5.254
Table 1 Tacrolimus intra-patient variability in heart transplantation: Main findings
Heart transplantation
Sample size
Donor type
Tac-IPV, assessment
Gueta et al[22], 201872DeceasedCVHigh trough level variability is associated with higher rates of graft rejection, and trough level variability during the first year is associated with increased risk of rejection after HT
Shuker et al[23], 201886DeceasedMADA high IPV was not associated with the development and progression of cardiac allograft vasculopathy or development of acute cellular rejection
González-Vílchez et al[24], 20221581DeceasedCVIPV levels had limited influence on mid-term outcomes in heart transplant, however high IPV may predispose to rejection in initially stable patients
Baker et al[25], 201967DeceasedTTRHigher TTR was not associated with a lower rate of Acute Cellular Rejection within the first 30 d after heart transplant
Pollock-Barziv et al[26], 2010144DeceasedSDAssociated Tac IPV with late rejection as well as worse patient and graft survival, but it is worth to mention that few heart transplant recipients were included in this study
Sirota et al[27], 2021118DeceasedSDSD ≥ 3 is associated with increased risk of poor outcomes
Table 2 Tacrolimus intra-patient variability in lung transplantation: main findings
Lung transplantation
Sample size
Donor type
Tac-IPV assessment
Gallagher et al[28], 2015110Non specifiedSDPatients with highly variable trough tacrolimus levels in the second half of the first post-transplant year will likely have similar variability in the second year and are at high risk for subsequent chronic lung allograft dysfunction and death
Kao et al[29], 2021157Non specifiedCV and TTRThe results suggest that tacrolimus TTR, time in therapeutic range, and variability are not related to the presence of ACR in LTRs
Ensor et al[30], 2018292Non specifiedTTRTacrolimus TTR was predictive of clinical outcomes of ACR, CLAD, infection, and death in lung transplant recipients at 1 yr in this investigation after adjusting for potential confounders
Katada et al[31], 202290Living and deceasedTTRA lower tacrolimus TTR is a predictor of late acute rejection
Table 3 Tacrolimus intra-patient variability and liver transplantation: Main findings
Liver transplantation
Sample size
Tac-IPV assessment
Lieber et al[18], 2013988Not specifiedSDNon-adherence among liver transplant recipients is associated with increased risk of graft failure
Stuber et al[19], 200896Not specifiedSDThe SD has utility of monitoring routine tac blood levels in pediatric recipients for detecting non-adherence prior to clinical rejection
Venkat et al[32], 2008101Not specifiedSDVariations in tac blood levels is associated with an increased risk of late allograft rejection in pediatric recipients
Shemesh et al[33], 2017400Both living and deceased donorSD; MLVIMLVI predicts late acute rejection in pediatric liver transplantation recipients
de Oliveira et al[34], 201750Both living and deceased donorSD; MLVIMLVI may be a nice indicator of the risk of medication non-adherence in child-age
Defrancq et al[35], 201941Both living and deceased donorCVHigh Tac IPV may be associated with adverse patient outcomes. Also, there is some impact of biological factors on IPV and therapy adherence
Christina et al[36], 2014150Not specifiedSD; MLVIThe MLVI is associated with and can predict rejection, possibly related to non-adherence in adult recipients
Del Bello et al[37], 2018116Deceased donor onlyCVTac IPV could be useful to identify patients with a greater risk of graft rejection and pf developing de novo DSA after liver transplantation
Rayar et al[38], 2018812Deceased donor onlyCVHigh CV of Tac concentrations was found to be predictive of Tac-related toxicity and poorer survival
van der Veer et al[39], 2019326Both living and deceased donorCVHigh IPV in Tac exposure beyond 6 mo after liver transplantation was not associated with imune-mediated graft injury
Dopazo et al[40], 2022140Deceased donor onlyCVHigh IPV between the third and sixth months appears to be an early and independent predictor of poorer liver transplant outcomes
Kim et al[41], 2022636Both living and deceased donorCVHigh Tac IPV was associated with increased risks of overall mortality and HCC recurrence in liver transplantation recipients with HCC
Table 4 Tacrolimus intra-patient variability and kidney transplantation: Main findings
Kidney transplantation
Sample size
Donor type
Tac-IPV assessment
Borra et al[47], 2010297Both living and deceased donorMADSignificant relationship between high Tac-IPV and long-term graft failure
Ro et al[45], 2012249Both living and deceased donorMADTAC IPV had a significant impact on rejection-free survival. The effect was influenced by CYP3A5 polymorphism
Sapir-Pichhadze et al[44], 2014356Both living and deceased donorMLVI/SDIncreased time-dependent TAC SD may be an independent risk factor for adverse kidney transplant outcomes
O’Regan et al[49], 2016394Both living and deceased donorCVInferior renal allograft survival was observed in recipients with higher Tac-IPV
Rodrigo et al[53], 2016310Deceased donor onlyCVTacrolimus level variability is a strong risk factor for dnDSA development and death-censored graft loss
Whalen et al[46], 2017376Both living and deceased donorMADHighly variable tacrolimus levels predict worse out- comes postrenal transplantation
Shuker et al[48], 2016808Both living and deceased donorMADA high tacrolimus IPV is an independent risk factor for adverse kidney transplant outcomes that can be used as an easy monitoring tool to help identify high-risk RTRs
Vanhove et al[56], 2016220Both living and deceased donorCV High IPV is related to accelerated progression of chronic histologic lesions before any evidence of renal dysfunction
Rozen-Zvi et al[51], 2017803Both living and deceased donorCVThe combination of high CV and exposure to low drug levels might identify high-risk patients in the early post-transplantation period
Goodall et al[50], 2017688Both living and deceased donorCVHigh tacrolimus IPV and clinic nonattendance are associated with inferior allograft survival
Sablik et al[62], 2018248Both living and deceased donorMADA high Tac IPV per se does not predispose to the development of chronic active antibody mediated rejection (c-aABMR) but is associated with inferior graft survival once c-aABMR is diagnosed
Seibert et al[57], 20181472Both living and deceased donorCVHigh variability of TAC dose increases risk of acute rejection. High variability of TAC trough increases risk of graft failure
Mo et al[54], 2019671Both living and deceased donorCVHigh IPV of Tac is associated with early deterioration of chronic histologic lesions as well as poorer long-term outcomes
Song et al[61], 20191241Living donor onlyTTRIncreasing the TTR of tacrolimus in the first year was associated with improved long-term outcomes in living kidney transplants, and TTR may be a novel valuable strategy to monitor tacrolimus exposure
Süsal et al[55], 20196638Deceased donor onlyCVEven in patients with good outcome during the first 3 post-transplant years, a high IPV was associated with inferior graft survival, indicating that a fluctuating tacrolimus trough level at years 1, 2 and 3 post-transplant is a major problem in kidney transplantation
Rahamimov et al[52], 2019878Both living and deceased donorCVMonitoring CV can help detect the high-risk patients
Gold et al[66], 20201419Deceased donor onlyMADA more intense and less variable exposure to tacrolimus could improve graft survival strongly in patients with high TAC IPV
Stefanović et al[58], 2020104Both living and deceased donorCVCombined assessment of tacrolimus IPV and tacrolimus C0/D may categorize patients towards risk of graft deterioration in the long-term post-transplantation period
Stefanović et al[59], 2021103Both living and deceased donorCVSimultaneous assessment of Tac IPV, C0/D, and CYP3A5 genotype may identify patients at risk of deterioration of graft function in the long-term post-transplantation period
Kim et al[65], 20211080Both living and deceased donorCVHigh tacrolimus IPV significantly increases the risk of graft failure and antibody mediated rejection in patients with high immunological risk
Park et al[63], 20211143Both living and deceased donorCVTAC-IPV can significantly affect allograft outcomes even with a high mean TAC-C0
Yin et al[64], 20221343Living donor onlyCVTac variability score is a novel measure of Tac IPV with higher correlation with graft survival and more convenience in clinical use than CV after kidney transplantation
Baghai Arassi et al[67], 202248Both living and deceased donorCVHigh Tac IPV is associated with an increased risk of dnDSA development and rejection episodes > year 1 posttransplant even in patients with low immunological risk profile
Nuchjumroon et al[60], 2022188Both living and deceased donorCVNo evidence that the CYP3A5 polymorphisms significantly influence tacrolimus IPV during the 6 to 12 mo after kidney transplantation
Table 5 Tacrolimus intra-patient variability in pancreas and bone marrow transplantation: Main findings
Kidney and pancreas, and bone marrow transplant
Sample size
Donor type
Tac-IPV Assessment
Torabi et al[69], 202039Both living and deceased donorCVThe once daily LCPT dosing may facilitate medication adherence and result in improved long-term outcomes
Marco et al[70], 2022128Living donor onlyCVDetermination of Tac IPV soon after alloHSCT could be useful in identifying greater risks of aGVHD