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A Retrospective Analysis of Immunosuppression Compliance, Dose Reduction and Discontinuation in Kidney Transplant Recipients
Open accessAbstract
We describe factors associated with poor compliance and dose reductions and examine the relative impact of compliance, dose reduction and discontinuation on graft outcome. Medicare claims for MMF in 7062 deceased donor renal recipients with at least 1 year of graft function were used to calculate compliance and dose reductions. Compliance was modeled using medication possession ratio to define quartiles for poor, low, medium and high compliance. The relative impact of compliance, dose reduction and discontinuation on graft outcome was assessed with Cox proportional hazards. Pediatric (Age 0-18, Odds ratio = 1.71, 95% CI 1.11-2.63, p = 0.014) and adolescent recipients (19-24, 1.57, 1.23-2.00, p < 0.001) were more likely poorly compliant compared to adults age 25-44. Poor compliance was also associated with physical limitations, hypertension, delayed graft function, rejection, infection and GI conditions. Poor (1.43, 1.11-1.84, p = 0.005) and low (1.46, 1.13-1.88, p = 0.004) compliance was associated with an increased hazard of graft loss as was >50% dose reduction (1.69, 1.15-2.50, p = 0.008) and discontinuation (8.34, 6.85-10.2, p < 0.001). Medication possession ratios lower than the 3-year mean were associated with an increased risk of graft loss. These results may indicate that interventions to improve compliance among kidney transplant recipients should strive for high rather than discourage low compliance.
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“Other groups used the discrepancy between immunosuppressant dosages and prescription refills or data from health insurances for the assessment of adherence[35,36].”
From Adherence is associated with a favorable outcome after lung transplantation (2019) · cites this paper as [36]
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“The patients with gastrointestinal adverse reactions have to reduce the dose or even stop mycophenolic acid treatment, which lead to an increased risk of rejection and affect the outcome of the transplantation (Knoll et al. 2003; Takemoto et al. 2007).”
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“Calculating the medication possession ratio is also feasible [20,21], but such data are not available to physicians in real-time.”
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“However, under current transplantation protocols, and despite non-adherence being so common (6) spontaneous tolerance is very rarely observed.”
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“Pediatric adolescent patients have even a higher (50% to 65%) rate of nonadherence to medications.(20) African-American patients as a function of socioeconomic class have repeatedly been shown to have noncompliance issues.”
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“Introduction Immunosuppressive medication nonadherence (MNA) in kidney transplant recipients leads to increased morbidity and mortality including rehospitalizations, acute and chronic rejection, transplant failure, and death.(1,2) These poor outcomes result in thousands of additional healthcare costs.”
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“Retrospective studies using Medicare data in the United States reported that low IPRs were associated with graft failure [11, 12, 15, 36].”
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“More recently, a once-daily, modified-release preparation of tacrolimus (Tac-QD, Advagraf, Astellas Pharma) has become available for clinical use [1,2].”
BackgroundAdherence to the Immunosuppressive Regimen in Adult and Pediatric Kidney Transplant Recipients
Dobbels, F., & Fine, R. Ν. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1690-7_22 · Cited by 2
Patient‐reported medication adherence and tolerability: Results of a prospective observational study
Keys, A., Pilch, N. A., Perez, C., Patel, N., Meadows, H. B., Fleming, J. N., & Taber, D. J. (2020) · JACCP JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACY · doi:10.1002/jac5.1365 · Cited by 2
“These are then multiplied together (1-25) to get a specific score for each side effect.”
BackgroundPatient self-management in kidney transplantation. definition, measurement, and intervention
Schäfer‐Keller, P. (2009) · edoc (University of Basel) · doi:10.5451/unibas-004970378 · Cited by 2
“Consensus, evidence-based guidelines recognize the clinical importance of nonadherence after renal transplantation, and recommend that transplant professionals should intervene to promote adherence [30].”
BackgroundInfluentialJyothindrakumar, J., Rajasekar, D., Natarajan, G., Thanigachalam, D. K., & Rajendran, P. (2021) · Indian Journal of Transplantation · doi:10.4103/ijot.ijot_123_20 · Cited by 1
Maizaud, F., Zava, S. A., Sayadi, H., Fromage, Y., Marquet, P., Woillard, J., & Monchaud, C. (2025) · PLoS ONE · doi:10.1371/journal.pone.0330854 · Cited by 1
Non Adherence – Non Response in der Transplantationsmedizin
Spengler, U. (2010) · Therapeutische Umschau · doi:10.1024/0040-5930/a000056 · Cited by 1
“Einnahmefehler bei der Immunsuppression sind ein Hauptfaktor für späte Abstoßungen und verkürzen das Überleben nach der Transplantation [6 – 8].”
BackgroundGuidelines and standards in medication adherence research
Bekker, C. L., Aslani, P., & Chen, T. F. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91888-6.00009-0 · Cited by 1
Abbas, A. A., Ahmed, M. E., Mohammed, S. M. E. H., Gar-Alnabi, S. S., Mohammed, W. A., Ahmed, M., Ahmed, M. H., & Badi, S. (2022) · Sudan Journal of Medical Sciences · doi:10.18502/sjms.v17i3.12085 · Cited by 1
Adherence in Pediatric Transplant Recipients
Foster, B. J. (2023) · Springer eBooks · doi:10.1007/978-981-19-6909-6_13 · Cited by 1
Terranella, S. L., Poirier, J., Chan, E. Y., Hertl, M., & Olaitan, O. K. (2020) · Annals of Transplantation · doi:10.12659/aot.924061 · Cited by 1
Taking a broader perspective on medication adherence : the importance of system factors
Berben, L. (2011) · edoc (University of Basel) · doi:10.5451/unibas-005676553 · Cited by 1
Clinical Allograft Rejection Syndromes in Kidney Transplantation
Nankivell, B. J. (2014) · Wiley eBooks · doi:10.1002/9781118873434.ch69
Maintenance Immunosuppressive Therapy
Hardinger, K. L., Brennan, D. C., & Klein, C. L. (2014) · doi:10.1002/9781118873434.ch66
Pharmacokinetics and Pharmacodynamics of Mycophenolate in Patients After Renal Transplantation
Rath, T., & Kpper, M. (2012) · InTech eBooks · doi:10.5772/26647
“In addition, gastrointestinal (GIT) side effects affect medical adherence of the patients with consecutive risk for graft failure (51).”
Background[Improved immunosuppression leads to better kidney transplantations].
Ekberg, H. (2012) · PubMed
Wang, C., Wang, G., Yi, H., Tan, J., Xu, C., Fang, X., Yang, Y., Li, H., Chen, Q., & Chen, G. (2013) · PLoS ONE · doi:10.1371/annotation/161a6145-d670-408a-a9fc-a1107b57724a
Rodrigues, L., Macario, F. J. G. R. M., Pêgo, C., Neves, M. R., Romãozinho, C., Santos, L., Alves, R., Machado, S., Mota, A., & Campos, M. (2015)
Kim, M., Malek, S. K., & Gabardi, S. (2012) · Nephrology times · doi:10.1097/01.nep.0000422753.61747.f0
Predictors Of Immunosuppressant Adherence In Long-term Renal Transplant Recipients
Galura, S. J. (2012) · Journal of International Crisis and Risk Communication Research
Special Considerations in Pediatric Transplant Patients
Schneider, L. M., Naclerio, C., & Conrad, C. (2018) · Springer eBooks · doi:10.1007/978-3-319-94914-7_46
Lang, S. (2021) · cIRcle (University of British Columbia) · doi:10.14288/1.0396860
Deng, Y., Zhang, Z., Hong, Y., Feng, L., Su, Y., & Xu, D. (2021) · Research Square · doi:10.21203/rs.3.rs-767385/v1
“The patients with gastrointestinal adverse reactions have to reduce the dose or even stop mycophenolic acid treatment, which lead to an increased risk of rejection and affect the outcome of the transplantation [3, 4].”
BackgroundADESÃO AO TRATAMENTO IMUNOSSUPRESSOR EM PACIENTES TRANSPLANTADOS RENAIS: REVISÃO DE LITERATURA
Zanetti, H. K., Gnatta, D., Rodrigues, M. F., de Oliveira, L. M., Heineck, I., Keitel, E. E., & Garcı́a, V. D. (2012) · Brazilian Journal of Transplantation · doi:10.53855/bjt.v15i3.185
Matas, A. J. (2007) · Brazilian Journal of Transplantation · doi:10.53855/bjt.v10i4.349
(2008) · Current Opinion in Organ Transplantation · doi:10.1097/mot.0b013e32830c93ae
Kuo, F.-C., Wu, T.-H., Loong, C., Lin, N., Ou, S., & Chen, C. (2022) · Journal of the Chinese Medical Association · doi:10.1097/jcma.0000000000000822
“17 This induces a vicious cycle of proinflammation, rejection, and new immune activation.”
ลาภเจริญ, พ. (2016) · Chula Digiverse · doi:10.58837/chula.the.2016.88
Gulati, S., Ray, D. S., Siddini, V., Kute, V. B., & Jadeja, Y. (2024) · Transplantation Proceedings · doi:10.1016/j.transproceed.2024.08.002
Schiliró, D., Tunbridge, M. J., Brown, N. J., Lopez, J., Tollison, T. S., Smith, E. D., Ladowski, J. M., Martinino, A., Hu, M., Schwalb, A. M., et al. (2026) · American Journal of Transplantation · doi:10.1016/j.ajt.2026.03.007
Pawelczak, P., Karakuła‐Juchnowicz, H., & Łukasik, P. (2014) · Current Problems of Psychiatry
Metadata
- Authors
- Takemoto, S. K., Pinsky, B. W., Schnitzler, M. A., Lentine, K. L., Willoughby, L. M., Burroughs, T. E., & Bunnapradist, S.
- Affiliations
- Saint Louis University (US)
- University of California, Los Angeles (US)
- Corresponding author
- Takemoto, S.K.
- Venue
- American Journal of Transplantation
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 7
- Issue
- 12
- Pages
- 2704-2711
- ISSN
- 1600-6135 (ISSN-L)
- OpenAlex
- W2020224358
- Cited by
- 202
- References
- 40
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 12 · 2020: 7 · 2019: 14 · 2018: 8 · 2017: 6 · 2016: 7 · 2015: 9 · 2014: 20 · 2013: 15 · 2012: 23
- FWCI
- 9.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Transplantation (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK073036)
- Topics
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Keywords
- kidney transplantation, medication possession ratio, mycophenolate mofetil, dose reduction, drug discontinuation, graft loss, graft rejection, delayed graft function, hypertension, gastrointestinal diseases
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Dose-Response Relationship, Drug, Gastrointestinal Diseases, Graft Rejection, Medicare, Humans, Immunosuppressive Agents, Infant, Infant, Newborn, Insurance Claim Review, Middle Aged, Mycophenolic Acid, Patient Compliance, Retrospective Studies, Risk Factors, United States, Logistic Models, Proportional Hazards Models, Kidney Transplantation, Treatment Outcome
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