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A Multifaceted Medication Adherence Promotion System to Reduce Late Kidney Allograft Rejection in Children and Young Adults

  • Andrew J. Benintende
    Affiliations
    Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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  • Michael S. Wolf
    Affiliations
    General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

    Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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  • Daniela P. Ladner
    Correspondence
    Address for Correspondence: Daniela Ladner, MD, MPH, Professor of Surgery, 676 N St. Clair St, Suite 1900, Chicago, IL 60611.
    Affiliations
    Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

    Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

    Division of Transplantation, Department of Surgery, Northwestern Medicine, Chicago, Illinois
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Published:January 11, 2022DOI:https://doi.org/10.1053/j.ajkd.2021.08.020
      Related Article, p. ∗∗∗
      Medication adherence is a complex issue that has complicated the optimal care of patients with chronic medical conditions.
      • Simpson R.J.
      Challenges for improving medication adherence.
      While kidney transplantation is a life-saving procedure, a third of the grafts fail within 5 years,
      • Wang J.H.
      • Skeans M.A.
      • Israni A.K.
      Current status of kidney transplant outcomes: dying to survive.
      and medication nonadherence is known to lead to late rejection and is a major contributor to graft loss 1 year after transplant.
      • Nevins T.E.
      • Nickerson P.W.
      • Dew M.A.
      Understanding medication nonadherence after kidney transplant.
      Recipients of solid organ transplantation undergo multiple significant life changes after transplantation, including being bound to a regimen of immunosuppressive medications, a requisite to protect the integrity of their transplant.
      • Shemesh E.
      • Duncan S.
      • Anand R.
      • et al.
      Trajectory of adherence behavior in pediatric and adolescent liver transplant recipients: the medication adherence in children who had a liver transplant cohort.
      To complicate the matter, immunosuppressive medications are often just some of the many medications patients need to take. We found that kidney transplant recipients on average need to manage 10 different medications per day.
      • Patzer R.E.
      • Serper M.
      • Reese P.P.
      • et al.
      Medication understanding, non-adherence, and clinical outcomes among adult kidney transplant recipients.
      ,
      • Serper M.
      • Patzer R.E.
      • Reese P.P.
      • et al.
      Medication misuse, nonadherence, and clinical outcomes among liver transplant recipients.
      Hence, optimizing medication management and adherence is of utmost importance. To date, no single intervention has proved to be highly effective at improving medication adherence, but a combination of interventions may be effective.
      • De Bleser L.
      • Matteson M.
      • Dobbels F.
      • Russell C.
      • De Geest S.
      Interventions to improve medication-adherence after transplantation: a systematic review.
      The pediatric and young adult populations have unique issues regarding medication adherence.
      • De Bleser L.
      • Matteson M.
      • Dobbels F.
      • Russell C.
      • De Geest S.
      Interventions to improve medication-adherence after transplantation: a systematic review.
      They generally have a guardian who bears some responsibility for ensuring they take their medication, and their barriers to taking medication may be different from adults, given their different lifestyles.
      • Shemesh E.
      • Duncan S.
      • Anand R.
      • et al.
      Trajectory of adherence behavior in pediatric and adolescent liver transplant recipients: the medication adherence in children who had a liver transplant cohort.
      ,
      • De Bleser L.
      • Matteson M.
      • Dobbels F.
      • Russell C.
      • De Geest S.
      Interventions to improve medication-adherence after transplantation: a systematic review.
      In this issue of AJKD, Hooper et al

      Hooper DK, Varnell CD Jr, Rich K, et al. A medication adherence promotion system to reduce late kidney allograft rejection: a quality improvement study. Am J Kidney Dis. Published online August 2, 2021. https://doi.org/10.1053/j.ajkd.2021.06.021

      addressed these unique problems with an intervention called the Medication Adherence Promotion System (MAPS), which aims to optimize the systems in place to improve medication adherence and reduce rejection rates in pediatric and young adult kidney transplant recipients. The MAPS intervention is based on previously published clinical trials in children
      • Foster B.J.
      • Pai A.
      • Zhao H.
      • Furth S.
      The TAKE-IT study: aims, design, and methods.
      • Foster B.J.
      • Pai A.L.H.
      • Zelikovsky N.
      • et al.
      A randomized trial of a multicomponent intervention to promote medication adherence: the Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT).
      • Grol R.
      • Grimshaw J.
      From best evidence to best practice: effective implementation of change in patients' care.
      and consists of 7 interdisciplinary quality improvement interventions 1 year after kidney transplant: (1) adherence promotion training for clinical team members, (2) electronic health record–supported adherence risk screening, (3) systematic assessment of barriers to taking medications, (4) designation of specific team members responsible to partner with patients to address barriers, (5) patient-centered shared decision-making to develop action plans, (6) planned follow-up to assess progress and adapt action plans, and (7) optional electronic adherence monitoring. The MAPS intervention was associated with a significant reduction in the acute rejection rate, from 1.61 rejections to 0.88 rejections per 100 patient-months (incidence rate ratio [IRR], 0.50 [95% CI, 0.27-0.91]; P = 0.02).
      The work reported by Hooper et al is a quality improvement (QI) study that focuses on clinical outcomes targeted by MAPS and involves a particularly vulnerable population of transplant recipients. Therefore, this effort to improve adherence, especially in this patient population, should be applauded. The QI nature of the study allows understanding of the real-world applications and potential scalability of evidence-based strategies for promoting adherence through melding of multiple factors within a hospital system.
      • Costa E.
      • Giardini A.
      • Savin M.
      • et al.
      Interventional tools to improve medication adherence: review of literature.
      However, a notable downside of this and other QI studies is that short-term, rather than long-term, outcomes are measured and reported.
      • Lindenauer P.K.
      Effects of quality improvement collaboratives.
      Another caveat is that the described MAPS intervention itself, and its many components, are not all proven approaches. Electronic monitoring, for example, can be very variable in its application. Electronic monitoring has been investigated over the past 2 decades as the solution to medication adherence, but without clear results.
      • Denhaerynck K.
      • Schäfer-Keller P.
      • Young J.
      • Steiger J.
      • Bock A.
      • De Geest S.
      Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients.
      ,
      • Kini V.
      • Ho P.M.
      Interventions to improve medication adherence: a review.
      Also, the use of electronic adherence monitors can be functionally challenging to assimilate into a patient’s daily life.
      • Kini V.
      • Ho P.M.
      Interventions to improve medication adherence: a review.
      This might explain why among the 28 patients who were offered electronic adherence monitoring, only 16 successfully used them over the study period. Furthermore, most kidney transplant recipients take more than just their immunosuppressive drugs, and electronic adherence monitoring can be cost-prohibitive, especially for multidrug regimens. The use of a regular pill box, versus an electronic monitoring tool, can be an effective alternative to support adherence.
      • Serper M.
      • Ladner D.P.
      • Curtis L.M.
      • et al.
      Transplant regimen adherence for kidney recipients by engaging information technologies (TAKE IT): rationale and methods for a randomized controlled trial of a strategy to promote medication adherence among transplant recipients.
      Another component of MAPS, clinical staff training, focuses on the patients’ care team. As it is described by Hooper et al, clinical staff training is a very diffuse intervention, and prior studies suggest that it has limited short-term efficacy at best. Hence, the short- and long-term efficacy of this element remains unclear. Hooper et al also proposed shared responsibility among the care team so that each member would address adherence barriers within their own specialty. This approach makes sense, but the lack of a centralized person, such as a nurse coordinator to triage the concerns, risks a fragmented approach.
      Moreover, it is likely that the semiannual assessments of adherence barriers proposed by Hooper et al may be too infrequent, especially for new patients. Nonadherence over a much shorter period of time can have detrimental effects, such as rejection and even graft loss. Furthermore, their analyses are clustered around a relatively small number of individuals. Many patients enter and exit the study during the evaluation period. While the inclusion of covariates is critical, this limits their inclusion. As such, for example, known psychosocial determinants at the patient level are not included, further limiting the study.
      Hooper et al should be commended for an important contribution focusing on a highly vulnerable patient population offering promising results utilizing MAPS. A strength of their study includes recognizing and addressing various intentional versus unintentional nonadherence issues. Also, contrary to many randomized controlled trials studying medication adherence, they measure highly important clinical outcomes—namely, rejection.
      • Foster B.J.
      • Pai A.
      • Zhao H.
      • Furth S.
      The TAKE-IT study: aims, design, and methods.
      • Foster B.J.
      • Pai A.L.H.
      • Zelikovsky N.
      • et al.
      A randomized trial of a multicomponent intervention to promote medication adherence: the Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT).
      • Grol R.
      • Grimshaw J.
      From best evidence to best practice: effective implementation of change in patients' care.
      More studies to better support kidney transplant recipients are necessary to avert medication nonadherence. Integrating some of the portions of MAPS in further studies and addressing potential risks could lead to more affordable solutions that can be broadly implemented.

      Article Information

      Authors’ Full Names and Academic Degrees

      Andrew J. Benintende, MD, Michael S. Wolf, PhD, MPH, and Daniela P. Ladner, MD, MPH.

      Support

      None.

      Financial Disclosure

      The authors declare that they have no relevant financial interests.

      Peer Review

      Received August 26, 2021 in response to an invitation from the journal. Accepted August 28, 2021 after editorial review by an Associate Editor and a Deputy Editor.

      References

        • Simpson R.J.
        Challenges for improving medication adherence.
        JAMA. 2006; 296: 2614-2616
        • Wang J.H.
        • Skeans M.A.
        • Israni A.K.
        Current status of kidney transplant outcomes: dying to survive.
        Adv Chronic Kidney Dis. 2016; 23: 281-286
        • Nevins T.E.
        • Nickerson P.W.
        • Dew M.A.
        Understanding medication nonadherence after kidney transplant.
        J Am Soc Nephrol. 2017; 28: 2290-2301
        • Shemesh E.
        • Duncan S.
        • Anand R.
        • et al.
        Trajectory of adherence behavior in pediatric and adolescent liver transplant recipients: the medication adherence in children who had a liver transplant cohort.
        Liver Transpl. 2018; 24: 80-88
        • Patzer R.E.
        • Serper M.
        • Reese P.P.
        • et al.
        Medication understanding, non-adherence, and clinical outcomes among adult kidney transplant recipients.
        Clin Transplant. 2016; 30: 1294-1305
        • Serper M.
        • Patzer R.E.
        • Reese P.P.
        • et al.
        Medication misuse, nonadherence, and clinical outcomes among liver transplant recipients.
        Liver Transpl. 2015; 21: 22-28
        • De Bleser L.
        • Matteson M.
        • Dobbels F.
        • Russell C.
        • De Geest S.
        Interventions to improve medication-adherence after transplantation: a systematic review.
        Transpl Int. 2009; 22: 780-797
      1. Hooper DK, Varnell CD Jr, Rich K, et al. A medication adherence promotion system to reduce late kidney allograft rejection: a quality improvement study. Am J Kidney Dis. Published online August 2, 2021. https://doi.org/10.1053/j.ajkd.2021.06.021

        • Foster B.J.
        • Pai A.
        • Zhao H.
        • Furth S.
        The TAKE-IT study: aims, design, and methods.
        BMC Nephrol. 2014; 15: 139
        • Foster B.J.
        • Pai A.L.H.
        • Zelikovsky N.
        • et al.
        A randomized trial of a multicomponent intervention to promote medication adherence: the Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT).
        Am J Kidney Dis. 2018; 72: 30-41
        • Grol R.
        • Grimshaw J.
        From best evidence to best practice: effective implementation of change in patients' care.
        Lancet. 2003; 362: 1225-1230
        • Costa E.
        • Giardini A.
        • Savin M.
        • et al.
        Interventional tools to improve medication adherence: review of literature.
        Patient Prefer Adherence. 2015; 9: 1303-1314
        • Lindenauer P.K.
        Effects of quality improvement collaboratives.
        BMJ. 2008; 336: 1448-1449
        • Denhaerynck K.
        • Schäfer-Keller P.
        • Young J.
        • Steiger J.
        • Bock A.
        • De Geest S.
        Examining assumptions regarding valid electronic monitoring of medication therapy: development of a validation framework and its application on a European sample of kidney transplant patients.
        BMC Med Res Methodol. 2008; 8: 5
        • Kini V.
        • Ho P.M.
        Interventions to improve medication adherence: a review.
        JAMA. 2018; 320: 2461-2473
        • Serper M.
        • Ladner D.P.
        • Curtis L.M.
        • et al.
        Transplant regimen adherence for kidney recipients by engaging information technologies (TAKE IT): rationale and methods for a randomized controlled trial of a strategy to promote medication adherence among transplant recipients.
        Contemp Clin Trials. 2021; 103: 106294