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.
“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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“For instance, if diabetes was the cause of end-stage renal disease (ESRD) or if it was indicated that the patient suffered from diabetes on the recipient registration survey, we considered that patient to be a diabetic.”
BackgroundIncidence and Predictors of Myocardial Infarction after Kidney Transplantation
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“The impact of poor compliance on graft outcome may be even greater in later periods after transplantation (37).”
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“We previously reported an increased risk of graft failure for kidney transplant recipients with GI complications whose MMF dose was reduced or discontinued (16,17).”
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BackgroundRENAL TRANSPLANT PATIENT COMPLIANCE WITH FREE IMMUNOSUPPRESSIVE MEDICATIONS1
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“The importance of strict compliance to treatment regimens for optimizing graft outcome has been well documented (1,2,20).”
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Griffin, K. J., & Elkin, T. D. (2001) · Pediatric Transplantation · doi:10.1034/j.1399-3046.2001.005004246.x · Cited by 101 · cited 1× · see citing works
“On the other hand, factors associated with poor compliance were consistent with other literature (5).”
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Chisholm, M. A. (2002) · Drugs · doi:10.2165/00003495-200262040-00002 · Cited by 95 · see citing works
HLA matching for kidney transplantation
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“The increased hazards after censoring at death with a functioning graft may indicate that poor compliance affects immune regulation rather than the general health of the recipient since a similar effect is seen with patients receiving HLA-matched transplants (32).”
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“The majority of studies have used surveys to obtain a patient self-report of compliance (1,2,10).”
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“In contrast, mycophenolate mofetil (MMF) is usually given at fixed doses since therapeutic drug monitoring was deemed unnecessary due to its favorable safety profile (22).”
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Willoughby, L. M., Fukami, S., Bunnapradist, S., Gavard, J. A., Lentine, K. L., Hardinger, K. L., Burroughs, T. E., Takemoto, S. K., & Schnitzler, M. A. (2006) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2006.00639.x · Cited by 46 · see citing works
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Transplant Outcomes and Economic Costs Associated with Patient Noncompliance to Immunosuppression
Pinsky, B. W., Takemoto, S., Lentine, K. L., Burroughs, T. E., Schnitzler, M. A., & Salvalaggio, P. R. D. O. (2009) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2009.02798.x · Cited by 331 · see citing works
“Using this methodology, we recently found that poor compliance with MMF was associated with 43–46% increased risk of graft failure (14).”
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“2007 (19) USA N = 40 (adolescents out of larger study) Retrospective analysis Prescription refill Medication possession ratio (MPR) over a 1–3-year time period (divided in quartiles using time dependent analysis): high adherence >98% MPR; medium between 81 and 98%, low between 69 and 81%; and poor: <69% 44% Adherence…”
BackgroundNonadherence Consensus Conference Summary Report
Fine, R. Ν., Becker, Y. T., Geest, S. D., Eisen, H. J., Ettenger, R. B., Evans, R., Rudow, D. L., McKay, D. B., Neu, A. M., Nevins, T. E., et al. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02495.x · Cited by 297 · see citing works
“<95% adherence to the immunosuppressive regimen) are sufficient to result in poor outcomes (10,14).”
BackgroundInterventions to improve medication-adherence after transplantation: a systematic review
Bleser, L. D., Matteson, M., Dobbels, F., Russell, C. L., & Geest, S. D. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00881.x · Cited by 248 · see citing works
“2 Counseling/behavioral interventions targeted, shaped, and/or reinforced behavior, empowered patients to participate in their care, positively changed a patient’s skill level or normal routine [3,7,8].”
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“Finally, transplant professionals require good quality instruments that do not pose an extra burden in terms of workload and time investment (7, 9) and that are reliable, valid, and responsive to change.”
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“Nonadherence was reported to be similar between the groups (16 % for African American recipients, compared to 9 %), but it was not stated how adherence was assessed and it is difficult to measure this accurately (Jensen et al. 2011; Takemoto et al. 2007).”
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“While the risk with non-adherence is a continuum, even very small degrees of non-adherence confer a significantly increased risk of graft rejection or graft loss [16,18].”
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“Evidence from previous research, showing that minimal deviations from the dosing schedule were associated with increased risk of late acute rejection episodes in adult heart (42) and renal (2,30) transplant recipients, supports this stringent cut-off.”
MethodResultLow, J. K., Williams, A. F., Manias, E., & Crawford, K. (2014) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfu204 · Cited by 158 · see citing works
“It is therefore evident that non-adherence not only increases the risk of hospitalization [26] but also causes poor long-term kidney outcomes [37], which negatively impact on the patient’s health and quality of life.”
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Rianthavorn, P., & Ettenger, R. B. (2005) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2005.00358.x · Cited by 147 · see citing works
Leino, A. D., King, E. C., Jiang, W., Vinks, A. A. T. M. M., Klawitter, J., Christians, U., Woodle, E. S., Alloway, R. R., & Rohan, J. M. (2018) · American Journal of Transplantation · doi:10.1111/ajt.15199 · Cited by 123 · see citing works
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“However, an autoregressive covariance structure (AR(1)) was incorporated into themodel to account for the influence of previous behavior”
BackgroundMethodWeng, F. L., Chandwani, S., Kurtyka, K., Zacker, C., Chisholm‐Burns, M. A., & Demissie, K. (2013) · BMC Nephrology · doi:10.1186/1471-2369-14-261 · Cited by 105 · see citing works
“clinicians’ collateral reports [30,31], serum assays for immunosuppressive medication concentrations [32-34], pill counts, and prescription refill and claims records [35].”
BackgroundPsychopathological aspects of kidney transplantation: Efficacy of a multidisciplinary team
Pasquale, C. D. (2014) · World Journal of Transplantation · doi:10.5500/wjt.v4.i4.267 · Cited by 101 · see citing works
Psychosocial Predictors of Mortality Following Lung Transplantation
Smith, P. J., Blumenthal, J. A., Trulock, E. P., Freedland, K. E., Carney, R. M., Davis, R. D., Hoffman, B. M., & Palmer, S. M. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13447 · Cited by 93 · see citing works
Prihodová, L., Nagyová, I., Rosenberger, J., Majerníková, M., Roland, R., Groothoff, J. W., & van Dijk, J. P. (2014) · Journal of Advanced Nursing · doi:10.1111/jan.12447 · Cited by 89 · see citing works
Dobbels, F., Decorte, A., Roskams, A., & Damme‐Lombaerts, R. V. (2009) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2009.01197.x · Cited by 88 · see citing works
“Limited evidence shows that a taking adherence of <98% is already sufficient to be associated with late acute rejections (13) and graft loss (14).”
Schmid‐Mohler, G., Thut, M. P., Wuthrich, R. P., Denhaerynck, K., & Geest, S. D. (2009) · Clinical Transplantation · doi:10.1111/j.1399-0012.2009.01056.x · Cited by 87 · see citing works
Factors Predictive of Medication Nonadherence After Renal Transplantation
Couzi, L., Moulin, B., Morin, M.-P., Albano, L., Godin, M., Barrou, B., Alamartine, É., Morélon, E., Girardot-Seguin, S., Mendes, L. P., et al. (2012) · Transplantation · doi:10.1097/tp.0b013e318271d7c1 · Cited by 83 · see citing works
“NA to immunosuppressive therapy is associated with a significant increase in serum creatinine level over time (5), an increased number of late acute rejections (5Y8), increased risk of graft loss (2, 7, 9, 10), and higher treatment costs (11).”
BackgroundMedication-taking among adult renal transplant recipients: barriers and strategies
Gordon, E. J., Gallant, M. P., Sehgal, A. R., Conti, D., & Siminoff, L. A. (2009) · Transplant International · doi:10.1111/j.1432-2277.2008.00827.x · Cited by 80 · see citing works
“Medication nonadherence is common, occurring in 5% to more than 45% of renal transplant recipients [5,11,12], and adherence declines over time [13].”
De Bleser, L., Dobbels, F., Berben, L., Vanhaecke, J., Verleden, G., Nevens, F., & De Geest, S. (2011) · Transplant International · doi:10.1111/j.1432-2277.2011.01296.x · Cited by 89 · see citing works
“First, the majority use a single NA measurement method; in the absence of a gold standard to assess medication NA, recent studies recommend a combination of assessment methods to enhance sensitivity [4,5].”
MethodAgid, O., Foussias, G., & Remington, G. J. (2010) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2010.499125 · Cited by 79 · see citing works
“Other reports involving chronic medical conditions such as diabetes, chronic obstructive pulmonary disease (COPD) and chronic kidney disease estimate medication nonadherence to be in the range of 40 -- 60% [17-19].”
BackgroundLerret, S. M., & Weiss, M. (2011) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2011.01536.x · Cited by 73 · see citing works
Graft Failure Due to Noncompliance Among 628 Kidney Transplant Recipients With Long-term Follow-up
Gaynor, J. J., Ciancio, G., Guerra, G., Sageshima, J., Hanson, L., Roth, D., Chen, L., Kupin, W. L., Mattiazzi, A. D., Tueros, L., et al. (2014) · Transplantation · doi:10.1097/01.tp.0000438199.76531.4a · Cited by 73 · see citing works
Joost, R., Dörje, F., Schwitulla, J., Eckardt, K., & Hugo, C. (2014) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfu207 · Cited by 72 · see citing works
“While recent literature demands adherence levels of up to 95% [11, 50], it remains the major question, how this can be achieved with justifiable effort.”
Backgroundvan Gelder, T., Meziyerh, S., Swen, J. J., de Vries, A. P. J., & Moes, D. J. A. R. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01142 · Cited by 71 · see citing works
“Furthermore, non-adherence is a strong predictor for poor outcome and is related to development of donor specific antibodies and a higher risk of rejection (Takemoto et al., 2007).”
BackgroundSocial support and immunosuppressant therapy adherence among adult renal transplant recipients
Chisholm‐Burns, M. A., Spivey, C. A., & Wilks, S. E. (2009) · Clinical Transplantation · doi:10.1111/j.1399-0012.2009.01060.x · Cited by 72 · see citing works
Morales, J. M., Varó, E., & Lázaro, P. (2011) · Clinical Transplantation · doi:10.1111/j.1399-0012.2011.01544.x · Cited by 70 · see citing works
Spivey, C. A., Chisholm‐Burns, M. A., Damadzadeh, B., & Billheimer, D. D. (2013) · Clinical Transplantation · doi:10.1111/ctr.12283 · Cited by 70 · see citing works
Gordon, E. J., PROHASKA, T. R., Gallant, M. P., Sehgal, A. R., Strogatz, D. S., Yucel, R. M., Conti, D., & Siminoff, L. A. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00917.x · Cited by 68 · see citing works
“The adverse effects on graft function of medication nonadherence [10,11] are well documented, as is cigarette smoking [12,13].”
BackgroundVanhove, T., Kuypers, D. R. J., Claes, K. J., Evenepoel, P., Meijers, B. K. I., Naesens, M., Vanrenterghem, Y. F. C., Cornelis, T., & Bammens, B. (2013) · Transplant International · doi:10.1111/tri.12133 · Cited by 66 · see citing works
Dharancy, S., Giral, M., Tétaz, R., Fatras, M., Dubel, L., & Pageaux, G. (2012) · Clinical Transplantation · doi:10.1111/j.1399-0012.2012.01652.x · Cited by 65 · see citing works
Bunnapradist, S., & Ambühl, P. M. (2008) · Clinical Transplantation · doi:10.1111/j.1399-0012.2008.00892.x · Cited by 64 · see citing works
“Interestingly, one study has investigated the effect of GI complications on patients adherence to the prescribed MMF regimen (20).”
BackgroundSelf-citationJaber, J. J., Feustel, P. J., Elbahloul, O., Conti, A. D., Gallichio, M. H., & Conti, D. J. (2006) · Clinical Transplantation · doi:10.1111/j.1399-0012.2006.00613.x · Cited by 62 · see citing works
Sustainability of Improvements in Medication Adherence through a Mobile Health Intervention
McGillicuddy, J. W., Taber, D. J., Mueller, M., Patel, S. K., Baliga, P. K., Chavin, K. D., Sox, L. R., Favela, A. P., Brunner-Jackson, B. M., & Treiber, F. A. (2015) · Progress in Transplantation · doi:10.7182/pit2015975 · Cited by 60 · see citing works
“Exclusion criteria included (1) inability to self-administer medications, (2) inability to measure own blood pressure, (3) inability to use a mobile phone, (4) history of psychiatric illness or substance abuse, (5) pregnant, lactating, or intending to become pregnant during the trial, (6) participant in another study,…”
Clinical consequences of non adherence to immunosuppressive medication in kidney transplant patients
Denhaerynck, K., Burkhalter, F., Schäfer‐Keller, P., Steiger, J. U., Bock, A., & Geest, S. D. (2009) · Transplant International · doi:10.1111/j.1432-2277.2008.00820.x · Cited by 62 · see citing works
“[12], who found a relationship between non adherence and poor outcomes in a mycophenolate mofetil-based regimen.”
BackgroundBiological and psychological differences in the child and adolescent transplant recipient
Hsu, D. T. (2005) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2005.00352.x · Cited by 58 · see citing works
Self-Reported Non-Adherence and Beliefs About Medication in a Swedish Kidney Transplant Population
Lennerling, A., & Forsberg, A. (2012) · The Open Nursing Journal · doi:10.2174/1874434601206010041 · Cited by 58 · see citing works
“For transplant recipients, even minor variations from the prescribed immunosuppressive therapy have been shown to be associated with an increased risk for poor outcome such as late acute rejections, poor function and graft loss [8-12].”
BackgroundLamba, S., Nagurka, R., Desai, K. K., Chun, S. J., Holland, B. K., & Koneru, B. (2011) · Clinical Transplantation · doi:10.1111/j.1399-0012.2011.01489.x · Cited by 57 · see citing works
Symptom experience, nonadherence and quality of life in adult liver transplant recipients.
Drent, G., Geest, S. D., Dobbels, F., KLEIBEUKER, J. H., & Haagsma, E. B. (2009) · PubMed · Cited by 50 · see citing works
Ciancio, G., Sageshima, J., Chen, L., Gaynor, J. J., Hanson, L., Tueros, L., Velarde, E. M., Gomez, C. M. B., Kupin, W. L., Guerra, G., et al. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2012.04235.x · Cited by 49 · see citing works
“Our results indicate that reduction or withholding of MMF contributed to the higher rate of acute rejection seen during the first 12 months in the MMF group, as inadequate MMF dosing has been associated with allograft loss due to acute rejection after kidney transplantation (18).”
ResultPost‐transplant adjustment – The later years
Fredericks, E. M., Zelikovsky, N., Aujoulat, I., Hames, A., & Wray, J. (2014) · Pediatric Transplantation · doi:10.1111/petr.12366 · Cited by 48 · see citing works
Chisholm, M. A., Mulloy, L. L., & DiPiro, J. T. (2004) · Clinical Transplantation · doi:10.1111/j.1399-0012.2004.00301.x · Cited by 44 · see citing works
Lung transplantation in Australia, 1986–2018: more than 30 years in the making
Paraskeva, M. A., Levin, K., Westall, G. P., & Snell, G. I. (2018) · The Medical Journal of Australia · doi:10.5694/mja17.00909 · Cited by 43 · see citing works
Cukor, D., Halen, N. V., Pencille, M., Tedla, F. M., & Salifu, M. O. (2016) · The Nephron journals/Nephron journals · doi:10.1159/000448627 · Cited by 42 · see citing works
Psychosocial predictors of medication adherence in pediatric heart and lung organ transplantation
Killian, M. (2017) · Pediatric Transplantation · doi:10.1111/petr.12899 · Cited by 41 · see citing works
Posttransplant Medical Adherence: What Have We Learned and Can We Do Better?
Dew, M. A., Posluszny, D. M., DiMartini, A. F., Myaskovsky, L., Steel, J. L., & Dabbs, A. D. (2018) · Current Transplantation Reports · doi:10.1007/s40472-018-0195-8 · Cited by 42 · see citing works
Factors Associated with Nonadherence to Medication in Kidney Transplant Recipients
Goldfarb‐Rumyantzev, A. S., Wright, S., Ragasa, R., Ostler, D., Orden, J. V., Smith, L. D., Ефимова, Е. А., Emerson, L. L., Sandhu, G. S., & Shihab, F. S. (2010) · Nephron Clinical Practice · doi:10.1159/000319645 · Cited by 41 · see citing works
“Having a living donor was predictive of worse adherence in our study. This outcome is consistent with most prior studies that found a similar association [”
ResultMEDICINE NON‐ADHERENCE IN KIDNEY TRANSPLANTATION
Williams, A. F., Manias, E., Gaskin, C. J., & Crawford, K. (2014) · Journal of Renal Care · doi:10.1111/jorc.12063 · Cited by 40 · see citing works
Russell, C. L., Ashbaugh, C., Peace, L. J., Çetingök, M., Hamburger, K. Q., Owens, S., Coffey, D., Webb, A. W., Hathaway, D., Winsett, R. P., et al. (2013) · Clinical Transplantation · doi:10.1111/ctr.12203 · Cited by 40 · see citing works
“Even minor deviations in adherence may lead to poor outcomes, although the dose–response of nonadherence and poor outcomes remains unclear (17, 19).”
BackgroundOperational tolerance in kidney transplantation and associated biomarkers
Massart, A., Ghisdal, L., Abramowicz, M. J., & Abramowicz, D. (2017) · Clinical & Experimental Immunology · doi:10.1111/cei.12981 · Cited by 39 · see citing works
“Finally, patient noncompliance (38) has been shown to significantly increase rates of late acute kidney rejection (38) and graft loss (39, 40).”
BackgroundMedication adherence in pediatric transplantation and assessment methods: a systematic review
Hoegy, D., Bleyzac, N., Robinson, P., Bertrand, Y., Dussart, C., & Janoly-Duménil, A. (2019) · Patient Preference and Adherence · doi:10.2147/ppa.s200209 · Cited by 38 · see citing works
“Assessment methodologies Period over which adherence was assessed The majority of studies (n=24) reported the period over which adherence was assessed; this ranged from 7 days(17,42) to 36 months.(15,18)The period was related to the method used: medication event monitoring systems (MEMS) generally examined adherence o…”
MethodSamojlik, M. M., & Stabler, C. L. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.05.039 · Cited by 38 · see citing works
Adherence to immunosuppression in adult lung transplant recipients: Prevalence and risk factors
Bosma, O. H., Vermeulen, K. M., Verschuuren, E. A., Erasmus, M. E., & van der Bij, W. (2011) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2011.05.007 · Cited by 40 · see citing works
Medication Adherence After Renal Transplantation—a Review of the Literature
Rebafka, A. (2016) · Journal of Renal Care · doi:10.1111/jorc.12181 · Cited by 37 · see citing works
Prevalence and determinants of physical activity and fluid intake in kidney transplant recipients
Gordon, E. J., PROHASKA, T. R., Gallant, M. P., Sehgal, A. R., Strogatz, D. S., Conti, D., & Siminoff, L. A. (2009) · Clinical Transplantation · doi:10.1111/j.1399-0012.2009.01154.x · Cited by 37 · see citing works
“It is well documented that patient behavior, such as medication adherence, is critical to successful management after kidney transplantation (9, 10).”
BackgroundPai, A. L. H., Rausch, J. R., Tackett, A. P., Marsolo, K. A., Drotar, D., & Goebel, J. (2012) · Pediatric Transplantation · doi:10.1111/j.1399-3046.2012.01657.x · Cited by 36 · see citing works
Bleser, L. D., Geest, S. D., Vandenbroeck, S., Vanhaecke, J., & Dobbels, F. (2010) · Sensors · doi:10.3390/s100301652 · Cited by 36 · see citing works
“In transplantation, for instance, taking less than 98% of the immunosuppressive doses results in significantly more graft losses [9].”
BackgroundTschida, S. J., Aslam, S., Khan, T. T., Sahli, B., Shrank, W. H., & Lal, L. S. (2013) · Journal of Managed Care Pharmacy · doi:10.18553/jmcp.2013.19.1.26 · Cited by 35 · see citing works
Ko, H., Kim, H. K., Chung, C. T. Y., Han, A., Min, S., Ha, J., & Min, S. (2021) · Scientific Reports · doi:10.1038/s41598-021-84868-5 · Cited by 35 · see citing works
Adherence is associated with a favorable outcome after lung transplantation
Bertram, A., Fuge, J., Suhling, H., Tudorache, I., Haverich, A., Welte, T., & Gottlieb, J. (2019) · PLoS ONE · doi:10.1371/journal.pone.0226167 · Cited by 34 · see citing works
“Other groups used the discrepancy between immunosuppressant dosages and prescription refills or data from health insurances for the assessment of adherence[35,36].”
MethodBurkhalter, H., Wirz‐Justice, A., Cajochen, C., Weaver, T. E., Steiger, J. U., Fehr, T. H., Venzin, R. M., & Geest, S. D. (2013) · Clinical Transplantation · doi:10.1111/ctr.12279 · Cited by 35 · see citing works
Heldenbrand, S. D., Li, C., Cross, R. P., DePiero, K. A., Dick, T. B., Ferguson, K., Kim, M., Newkirk, E. N., Park, J. M., Kerr, J., et al. (2016) · Transplant Infectious Disease · doi:10.1111/tid.12609 · Cited by 33 · see citing works
Corr, M., Walker, A., Maxwell, A. P., & McKay, G. J. (2024) · Transplantation Reviews · doi:10.1016/j.trre.2024.100900 · Cited by 32 · see citing works
Influence of Pill Burden and Drug Cost on Renal Function After Transplantation
Hardinger, K. L., Hutcherson, T. C., Preston, D., & Murillo, D. (2012) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/j.1875-9114.2012.01032.x · Cited by 31 · see citing works
Brahm, M. M. T., Manfro, R. C., de Mello, D., Cioato, S. G., & Gonçalves, L. F. S. (2012) · Transplantation Proceedings · doi:10.1016/j.transproceed.2012.08.001 · Cited by 30 · see citing works
Low, J. K., Crawford, K., Manias, E., & Williams, A. F. (2016) · Journal of Clinical Nursing · doi:10.1111/jocn.13435 · Cited by 28 · see citing works
Tielen, M., van Exel, J. N. A., van Buren, M. C., Maasdam, L., & Weimar, W. W. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq642 · Cited by 27 · see citing works
“Non-adherence has been shown to be related to rejection and even graft failure [7–10].”
BackgroundBoucquemont, J., Pai, A. L. H., Dharnidharka, V. R., Hébert, D., Zelikovsky, N., Amaral, S. G., Furth, S. L., & Foster, B. J. (2019) · American Journal of Transplantation · doi:10.1111/ajt.15590 · Cited by 27 · see citing works
A New Electronic Monitoring Device to Measure Medication Adherence: Usability of the Helping Hand™
De Bleser, L., Vincke, B., Dobbels, F., Happ, M. B., Maes, B., Vanhaecke, J., & De Geest, S. (2010) · Sensors · doi:10.3390/s100301535 · Cited by 26 · see citing works
“These stringent cut-off values are based on previous work showing that minor deviations from dosing schedule are associated with late acute rejections [7,8].”
BackgroundTerebelo, S., & MARKELL, M. S. (2010) · Transplantation Proceedings · doi:10.1016/j.transproceed.2010.08.027 · Cited by 26 · see citing works
Evaluation of a transplantation specialty pharmacy program
Hlubocky, J., Stuckey, L. J., Schuman, A., & Stevenson, J. G. (2012) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp110350 · Cited by 26 · see citing works
Lehner, L. J., Reinke, P., Hörstrup, J. H., Rath, T., Suwelack, B. M., Krämer, B. K., Budde, K., & Banas, B. (2017) · Clinical Transplantation · doi:10.1111/ctr.13142 · Cited by 26 · see citing works
Saint‐Marcoux, F., Woillard, J., Monchaud, C., Friedl, J., Bocquentin, F., Essig, M., & Marquet, P. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.08.020 · Cited by 25 · see citing works
Tang, J., Kerklaan, J., Wong, G., Howell, M., Scholes-Robertson, N. J., Guha, C., Kelly, A., & Tong, A. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16613 · Cited by 25 · see citing works
Gruttadauria, S., Grosso, G., Mistretta, A., Pagano, D., Scianna, G., Vizzini, G. B., Cintorino, D., Spada, M., Basile, F., & Gridelli, B. G. (2011) · Digestive and Liver Disease · doi:10.1016/j.dld.2011.06.017 · Cited by 25 · see citing works
Inosine Monophosphate Dehydrogenase Polymorphisms and Renal Allograft Outcome
Shah, S., Harwood, S., Döhler, B., Opelz, G., & Yaqoob, M. (2012) · Transplantation · doi:10.1097/tp.0b013e31825b7654 · Cited by 25 · see citing works
“C1842928 IVS 7 (10) 819+10 A9G rs11706052 Intron 7 IMPDH II CCACCTGTGT[A/ G]GCAGCTCACC 19”
Brar, A., Babakhani, A., Salifu, M. O., & Jindal, R. M. (2014) · Transplantation Proceedings · doi:10.1016/j.transproceed.2013.12.051 · Cited by 25 · see citing works
Psychosocial diagnosis and treatment before and after organ transplantation
de Zwaan, M., Erim, Y., Kröncke, S., Vitinius, F., Buchholz, A., & Nöhre, M. (2023) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.m2023.0087 · Cited by 24 · see citing works
Teng, S., Shuping, Z., Zhang, W., Lin, X., Shang, Y., Peng, X., & Liu, H. (2015) · Journal of Nursing Scholarship · doi:10.1111/jnu.12157 · Cited by 24 · see citing works
“Medication adherence is an important issue for organ transplant recipients, and nonadherence to immunosuppressive medication is one of the causes of acute rejection and graft loss (Denhaerynck et al., 2005; Gaynor et al., 2014; Takemoto, 2007).”
Backgroundde Brito, D. C. S., Marsicano, E. O., Grincenkov, F. R. D. S., Colugnati, F. A. B., Lucchetti, G., & Sanders‐Pinheiro, H. (2015) · Sao Paulo Medical Journal · doi:10.1590/1516-3180.2015.01071008 · Cited by 24 · see citing works
“0% (19) 1 Palliative coping 52% (13) 24.”
Russell, C. L., Moore, S. M., Hathaway, D., Cheng, A.-L., Chen, G., & Goggin, K. (2016) · BMC Nephrology · doi:10.1186/s12882-016-0285-8 · Cited by 24 · see citing works
What is the intrapatient variability of mycophenolic acid trough levels?
Todorova, E. K., Huang, S. S., Kobrzyński, M., & Filler, G. (2015) · Pediatric Transplantation · doi:10.1111/petr.12559 · Cited by 23 · see citing works
“An added challenge is the decreased immunosuppression compliance in pediatric and particularly adolescent patients as compared to adults (34).”
BackgroundCOOPER, M. M., Salvadori, M., Budde, K., Oppenheimer, F., Sollinger, H. W., & Zeier, M. (2012) · Transplantation Reviews · doi:10.1016/j.trre.2012.02.001 · Cited by 23 · see citing works
“Rates of dose reduction and/or discontinuations of MMF are consistently high [18,21,22] and have been demonstrated to be associated with a significantly increased risk of acute rejection and graft loss [18-25].”
BackgroundMedication compliance and lifestyle adherence in renal transplant recipients in Kuwait
Kenawy, A. S., Gheith, O. A. A., Al-Otaibi, T., Othman, N. F., Abo-Atya, H., Al-Otaibi, M., & Nagy, M. S. (2019) · Patient Preference and Adherence · doi:10.2147/ppa.s209212 · Cited by 22 · see citing works
“4,5,17 Our fi nding was also far lower than the prevalence of good compliance noticed by Gheith et al, with 97% compliance with immunosuppressants.”
Israni, A. K., Weng, F. L., Cen, Y., Joffe, M., Kamoun, M., & Feldman, H. I. (2010) · Clinical Transplantation · doi:10.1111/j.1399-0012.2010.01340.x · Cited by 22 · see citing works
Wilks, S. E., Spivey, C. A., & Chisholm‐Burns, M. A. (2010) · Journal of Evaluation in Clinical Practice · doi:10.1111/j.1365-2753.2008.01115.x · Cited by 22 · see citing works
Vaňková, B., Ribaut, J., Dobbels, F., Gerull, S., Malá‐Ládová, K., Zullig, L. L., & Geest, S. D. (2021) · Transplantation Reviews · doi:10.1016/j.trre.2021.100671 · Cited by 23 · see citing works
Su, V., Greanya, E. D., & Ensom, M. H. H. (2011) · Annals of Pharmacotherapy · doi:10.1345/aph.1p456 · Cited by 22 · see citing works
Symptom Experienced Three Years after Liver Transplantation under Immunosuppression in Adults
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/journal.pone.0080584 · Cited by 21 · see citing works
“A link between symptom experience and nonadherence has been found in patients who have undergone other types of organ transplantations, such as heart, renal, and lung transplantations [13,17,24-26].”
BackgroundRetractedTransplant recipients are vulnerable to coverage denial under Medicare Part D
Potter, L., Maldonado, A. Q., Lentine, K. L., Schnitzler, M. A., Zhang, Z., Hess, G. P., Garrity, E. R., Kasiske, B. L., & Axelrod, D. A. (2018) · American Journal of Transplantation · doi:10.1111/ajt.14703 · Cited by 21 · see citing works
Self-citationMedication adherence in successful kidney transplant recipients.
Ruppar, T. M., & Russell, C. L. (2009) · PubMed · doi:10.1177/152692480901900211 · Cited by 20 · see citing works
Increasing adherence to immunosuppression: a clinical priority
Geest, S. D., & Dobbels, F. (2010) · Nature Reviews Nephrology · doi:10.1038/nrneph.2010.11 · Cited by 20 · see citing works
“Increasing evidence suggests that nonadherence increases the risk of poor outcomes, particularly after kidney and heart transplantation”
Andrés, A., Delgado-Arranz, M., Morales, E., Dipalma, T., Polanco, N., Gutiérrez-Solís, E., Morales, J. M., Praga, M., Gutiérrez, E., & González, E. (2010) · Transplantation Proceedings · doi:10.1016/j.transproceed.2010.07.044 · Cited by 18 · see citing works
Medication adherence in successful kidney transplant recipients
Ruppar, T. M., & Russell, C. L. (2009) · Progress in Transplantation · doi:10.7182/prtr.19.2.2652p03x0vvx7665 · Cited by 18 · see citing works
Reinke, P., Budde, K., Hugo, C., Petersen, P., Schnuelle, P., Fricke, L., Scholz, D., Sperschneider, H., Bahner, U., Kramer, S., et al. (2011) · Transplantation Proceedings · doi:10.1016/j.transproceed.2011.01.184 · Cited by 17 · see citing works
Adherence in Adolescent and Young Adult Kidney Transplant Recipients
Bethany, J., & Ahna, L. H. P. (2014) · The Open Urology & Nephrology Journal · doi:10.2174/1874303x014070100133 · Cited by 22 · see citing works
“6 times higher in those 19-24 years than among those 25-44 years old [15].”
InfluentialSterneck, M. R., Settmacher, U., Ganten, T. M., Sarrazin, C., Speidel, N., Broering, D., Heyne, N., Paulus, E., Mertens, M., & Fischer, L. (2014) · Transplantation Proceedings · doi:10.1016/j.transproceed.2013.09.026 · Cited by 17 · see citing works
- 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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