Skip to main content
Log in

Factors relevant to medication non-adherence in kidney transplant: a systematic review

  • Review Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Medication non-adherence is a major issue after transplant that can lead to misdiagnosis, rejection, poor health affecting quality of life, graft loss or death. Several estimations of adherence and related factors have previously been described but conclusions leave doubt as to the most accurate assessment method. Aim of the review To identify the factors most relevant to medication non-adherence in kidney transplant in current clinical practice. Method This systematic review is registered in the PROSPERO data base and follows the Prisma checklist. Articles in English in three databases from January 2009 to December 2014 were analysed. A synthesis was made to target adherence assessment methods, their prevalence and significance. Results Thirty-seven studies were analysed rates of non-adherence fluctuating from 1.6 to 96%. Assessment methods varied from one study to another, although self-reports were mainly used. It appears that youth (≤50 years old), male, low social support, unemployment, low education, ≥3 months post graft, living donor, ≥6 comorbidities, ≥5 drugs/d, ≥2 intakes/d, negative beliefs, negative behavior, depression and anxiety were the factors significantly related to non-adherence. Conclusion As there are no established guidelines, consideration should be given to more than one approach to identify medication non-adherence although self-reports should remain the cornerstone of adherence assessment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Tielen M, van Exel NJA, van Buren MC, Maasdam L, Weimar W. Attitudes towards medication non-adherence in elderly kidney transplant patients: a Q methodology study. Nephrol Dial Transplant. 2011;26:1723–8.

    Article  PubMed  Google Scholar 

  2. Brahm MMT, Manfro RC, Mello D, Cioato S, Gonçalves LFS. Evaluation of adherence to immunosuppressive drugs in kidney transplantation by control of medication dispensing. Transplant Proc. 2012;44:2391–3.

    Article  CAS  PubMed  Google Scholar 

  3. Chisholm-Burns MA, Spivey CA, Wilks SE. Social support and immunosuppressant therapy adherence among adult renal transplant recipients. Clin Transplant. 2010;24:312–20.

    Article  PubMed  Google Scholar 

  4. Denhaerynck K, Dobbels F, Cleemput I, Desmyttere A, Schäfer-Keller P, Schaub S, et al. Prevalence, consequences, and determinants of nonadherence in adult renal transplant patients: a literature review. Transpl Int. 2005;18:1121–33.

    Article  PubMed  Google Scholar 

  5. Dharancy S, Giral M, Tetaz R, Fatras M, Dubel L, Pageaux G-P. Adherence with immunosuppressive treatment after transplantation: results from the French trial PREDICT. Clin Transplant. 2012;26:E293–9.

    Article  PubMed  Google Scholar 

  6. Gordon EJ, Gallant M, Sehgal AR, Conti D, Siminoff LA. Medication-taking among adult renal transplant recipients: barriers and strategies. Transpl Int Off J Eur Soc Organ Transplant. 2009;22:534–45.

    Article  Google Scholar 

  7. Hardinger KL, Hutcherson T, Preston D, Murillo D. Influence of pill burden and drug cost on renal function after transplantation. Pharmacotherapy. 2012;32:427–32.

    Article  PubMed  Google Scholar 

  8. Pinsky BW, Takemoto SK, Lentine KL, Burroughs TE, Schnitzler MA, Salvalaggio PR. Transplant outcomes and economic costs associated with patient noncompliance to immunosuppression. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2009;9:2597–606.

    Article  CAS  Google Scholar 

  9. Couzi L, Moulin B, Morin M-P, Albano L, Godin M, Barrou B, et al. Factors predictive of medication nonadherence after renal transplantation: a French observational study. Transplantation. 2013;95:326–32.

    Article  PubMed  Google Scholar 

  10. Russell C, Conn V, Ashbaugh C, Madsen R, Wakefield M, Webb A, et al. Taking immunosuppressive medications effectively (TIMELink): a pilot randomized controlled trial in adult kidney transplant recipients. Clin Transplant. 2011;25:864–70.

    Article  PubMed  Google Scholar 

  11. Goldfarb-Rumyantzev AS, Wright S, Ragasa R, Ostler D, Van Orden J, Smith L, et al. Factors associated with nonadherence to medication in kidney transplant recipients. Nephron Clin Pract. 2011;117:c33–9.

    Article  PubMed  Google Scholar 

  12. Germani G, Lazzaro S, Gnoato F, Senzolo M, Borella V, Rupolo G, et al. Nonadherent behaviors after solid organ transplantation. Transplant Proc. 2011;43:318–23.

    Article  CAS  PubMed  Google Scholar 

  13. De Geest S, Dobbels F. Transplantation: increasing adherence to immunosuppression: a clinical priority. Nat Rev Nephrol. 2010;6:139–40.

    Article  PubMed  Google Scholar 

  14. Terebelo S, Markell M. Preferential adherence to immunosuppressive over nonimmunosuppressive medications in kidney transplant recipients. Transplant Proc. 2010;42:3578–85.

    Article  CAS  PubMed  Google Scholar 

  15. Griva K, Davenport A, Harrison M, Newman SP. Non-adherence to immunosuppressive medications in kidney transplantation: intent vs. forgetfulness and clinical markers of medication intake. Ann Behav Med. 2012;44:85–93.

    Article  PubMed  Google Scholar 

  16. Fine RN, Becker Y, De Geest S, Eisen H, Ettenger R, Evans R, et al. Nonadherence consensus conference summary report. Am J Transplant. 2009;9:35–41.

    Article  CAS  PubMed  Google Scholar 

  17. Hugon A, Roustit M, Lehmann A, Saint-Raymond C, Borrel E, Hilleret M-N, et al. Influence of intention to adhere, beliefs and satisfaction about medicines on adherence in solid organ transplant recipients. Transplantation. 2014;98:222–8.

    Article  PubMed  Google Scholar 

  18. The express scripts. 2014 Drug Trend Report. 14-EME27270. Available from: https://www.google.fr/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwiFzti3joXRAhXDsxQKHSIkAPEQFggaMAA&url=http%3A%2F%2Flab.express-scripts.com%2F~%2Fmedia%2FPDFs%2FDrug%2520Trend%2520Report%2FExpressScripts_DrugTrendReport.ashx&usg=AFQjCNFMm2ea1pg0vV62TL0oJPRH0c3O8g&sig2=tt0y89ea7ntS8dcfYkCytw&cad=rja. Last seen 29th Dec 2016.

  19. Dew MA, Dabbs AD, Myaskovsky L, Shyu S, Shellmer DA, DiMartini AF, et al. Meta-analysis of medical regimen adherence outcomes in pediatric solid organ transplantation. Transplantation. 2009;88:736–46.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mathis AS. Managed care implications of improving long-term outcomes in organ transplantation. Am J Manag Care. 2015;21:s24–30.

    PubMed  Google Scholar 

  21. Russell CL, Cetingok M, Hamburger KQ, Owens S, Thompson D, Hathaway D, et al. Medication adherence in older renal transplant recipients. Clin Nurs Res. 2010;19:95–112.

    Article  PubMed  Google Scholar 

  22. Carrasco FR, Moreno A, Ridao N, Calvo N, Pérez-Flores I, Rodríguez A, et al. Kidney transplantation complications related to psychiatric or neurological disorders. Transplant Proc. 2009;41:2430–2.

    Article  CAS  PubMed  Google Scholar 

  23. World Health Organisation. Adherence to long-term therapies. 2003. ISBN 92 4 154599 2. http://www.who.int/chp/knowledge/publications/adherence_full_report.pdf?ua=1. Last seen 29th Dec 2016.

  24. Vrijens B, De Geest S, Hughes DA, Przemyslaw K, Demonceau J, Ruppar T, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012;73:691–705.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Baudrant-Boga M, Lehmann A, Allenet B. Thinking differently the patient medication compliance: from an injunctive posture to a working alliance between the patient and the healthcare provider: concepts and determinants. Ann Pharm Fr. 2012;70:15–25.

    Article  CAS  PubMed  Google Scholar 

  26. Prendergast MB, Gaston RS. Optimizing medication adherence: an ongoing opportunity to improve outcomes after kidney transplantation. Clin J Am Soc Nephrol. 2010;5:1305–11.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Spivey CA, Chisholm-Burns MA, Damadzadeh B, Billheimer D. Determining the effect of immunosuppressant adherence on graft failure risk among renal transplant recipients. Clin Transplant. 2014;28:96–104.

    Article  CAS  PubMed  Google Scholar 

  28. Russell CL, Owens S, Hamburger KQ, Thompson DA, Leach RR, Cetingok M, et al. Medication adherence and older renal transplant patients’ perceptions of electronic medication monitoring. J Gerontol Nurs. 2009;35:17–21.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Israni AK, Weng FL, Cen Y-Y, Joffe M, Kamoun M, Feldman HI. Electronically measured adherence to immunosuppressive medications and kidney function after deceased donor kidney transplantation. Clin Transplant. 2011;25:E124–31. doi:10.1111/j.1399-0012.2010.01340.x.

    Article  PubMed  Google Scholar 

  30. The Consort Statement 2010. http://www.consort-statement.org/. Last seen 29th Dec 2016.

  31. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Last seen 29th December 2016.

  32. Blaxter M. Criteria for the evaluation of qualitative research papers. Medical Sociology News. 1996. http://www.medicalsociologyonline.org/resources/Vol7Iss1/7.1-Criteria-for-evaluating_Blaxter.pdf. Last seen 29th December 2016.

  33. Jindal RM, Neff RT, Abbott KC, Hurst FP, Elster EA, Falta EM, et al. Association between depression and nonadherence in recipients of kidney transplants: analysis of the United States renal data system. Transplant Proc. 2009;41:3662–6.

    Article  CAS  PubMed  Google Scholar 

  34. Gelb SR, Shapiro RJ, Thornton WJL. Predicting medication adherence and employment status following kidney transplant: the relative utility of traditional and everyday cognitive approaches. Neuropsychology. 2010;24:514–26.

    Article  PubMed  Google Scholar 

  35. Denhaerynck K, Burkhalter F, Schäfer-Keller P, Steiger J, Bock A, De Geest S. Clinical consequences of non adherence to immunosuppressive medication in kidney transplant patients. Transpl Int. 2009;22:441–6.

    Article  PubMed  Google Scholar 

  36. Joost R, Dörje F, Schwitulla J, Eckardt K-U, Hugo C. Intensified pharmaceutical care is improving immunosuppressive medication adherence in kidney transplant recipients during the first post-transplant year: a quasi-experimental study. Nephrol Dial Transplant. 2014;29:1597–607.

    Article  PubMed  Google Scholar 

  37. Ortega F, Otero A, Crespo JF, Delgado JF, Borro JM, Cuervo J, et al. Satisfaction and adherence with immunosuppressant treatment in renal transplant patients living with a working graft. J Nephrol. 2013;26:297–305.

    Article  PubMed  Google Scholar 

  38. Constantiner M, Cukor D. Barriers to immunosuppressive medication adherence in high-risk adult renal transplant recipients. Dial Transplant. 2011;40:60–6. doi:10.1002/dat.20536.

    Article  Google Scholar 

  39. Ruppar TM, Russell CL. Medication adherence in successful kidney transplant recipients. Prog Transplant. 2009;19:167–72.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Eisenberger U, Wüthrich RP, Bock A, Ambühl P, Steiger J, Intondi A, et al. Medication adherence assessment: high accuracy of the new Ingestible Sensor System in kidney transplants. Transplantation. 2013;96:245–50.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Gaynor JJ, Ciancio G, Guerra G, Sageshima J, Hanson L, Roth D, et al. Graft failure due to noncompliance among 628 kidney transplant recipients with long-term follow-up: a single-center observational study. Transplantation. 2014;97:925–33.

    Article  PubMed  Google Scholar 

  42. Burkhalter H, Wirz-Justice A, Cajochen C, Weaver TE, Steiger J, Fehr T, et al. Daytime sleepiness in renal transplant recipients is associated with immunosuppressive non-adherence: a cross-sectional, multi-center study. Clin Transplant. 2014;28:58–66. doi:10.1111/ctr.12279.

    Article  PubMed  Google Scholar 

  43. Obi Y, Ichimaru N, Kato T, Kaimori J-Y, Okumi M, Yazawa K, et al. A single daily dose enhances the adherence to immunosuppressive treatment in kidney transplant recipients: a cross-sectional study. Clin Exp Nephrol. 2013;17:310–5.

    Article  CAS  PubMed  Google Scholar 

  44. Shabany Hamedan M, Mohamad Aliha J. Relationship between immunosuppressive medications adherence and quality of life and some patient factors in renal transplant patients in Iran. Glob J Health Sci. 2014;6:205–12.

    Article  PubMed  Google Scholar 

  45. Van Boekel GAJ, Kerkhofs CHH, Hilbrands LB. Treatment satisfaction in renal transplant patients taking tacrolimus once daily. Clin Ther. 2013;35:1821–1829e1.

    Google Scholar 

  46. Massey EK, Tielen M, Laging M, Beck DK, Khemai R, van Gelder T, et al. The role of goal cognitions, illness perceptions and treatment beliefs in self-reported adherence after kidney transplantation: a cohort study. J Psychosom Res. 2013;75:229–34.

    Article  PubMed  Google Scholar 

  47. Chisholm-Burns M, Pinsky B, Parker G, Johnson P, Arcona S, Buzinec P, et al. Factors related to immunosuppressant medication adherence in renal transplant recipients. Clin Transplant. 2012;26:706–13.

    Article  PubMed  Google Scholar 

  48. Russell CL, Ashbaugh C, Peace L, Cetingok M, Hamburger KQ, Owens S, et al. Time-in-a-bottle (TIAB): a longitudinal, correlational study of patterns, potential predictors, and outcomes of immunosuppressive medication adherence in adult kidney transplant recipients. Clin Transplant. 2013;27:E580–90.

    Article  PubMed  Google Scholar 

  49. Lin S-Y, Fetzer SJ, Lee P-C, Chen C-H. Predicting adherence to health care recommendations using health promotion behaviours in kidney transplant recipients within 1–5 years post-transplant. J Clin Nurs. 2011;20:3313–21.

    Article  PubMed  Google Scholar 

  50. Sabbatini M, Garofalo G, Borrelli S, Vitale S, Torino M, Capone D, et al. Efficacy of a reduced pill burden on therapeutic adherence to calcineurin inhibitors in renal transplant recipients: an observational study. Patient Prefer Adherence. 2014;8:73–81.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Weng FL, Chandwani S, Kurtyka KM, Zacker C, Chisholm-Burns MA, Demissie K. Prevalence and correlates of medication non-adherence among kidney transplant recipients more than 6 months post-transplant: a cross-sectional study. BMC Nephrol. 2013;14:261.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Nevins TE, Robiner WN, Thomas W. Predictive patterns of early medication adherence in renal transplantation. Transplantation. 2014;98:878–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Cheng C-Y. Lin BY-J, Chang K-H, Shu K-H, Wu M-J. Awareness of memory impairment increases the adherence to immunosuppressants in kidney transplant recipients. Transplant Proc. 2012;44:746–8.

    Article  PubMed  Google Scholar 

  54. Tsapepas D, Langone A, Chan L, Wiland A, McCague K, Chisholm-Burns M. A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study. Ann Transplant. 2014;19:174–81.

    Article  PubMed  Google Scholar 

  55. Lalić J, Veličković-Radovanović R, Mitić B, Paunović G, Cvetković T. Immunosuppressive medication adherence in kidney transplant patients. Med Princ Pract. 2014;23:351–6.

    Article  PubMed  Google Scholar 

  56. Kuypers DRJ, Peeters PC, Sennesael JJ, Kianda MN, Vrijens B, Kristanto P, et al. Improved adherence to tacrolimus once-daily formulation in renal recipients: a randomized controlled trial using electronic monitoring. Transplantation. 2013;95:333–40.

    Article  CAS  PubMed  Google Scholar 

  57. Cukor D, Rosenthal DS, Jindal RM, Brown CD, Kimmel PL. Depression is an important contributor to low medication adherence in hemodialyzed patients and transplant recipients. Kidney Int. 2009;75:1223–9.

    Article  PubMed  Google Scholar 

  58. Williams AF, Manias E, Gaskin CJ, Crawford K. Medicine non-adherence in kidney transplantation. J Ren Care. 2014;40:107–16.

    Article  PubMed  Google Scholar 

  59. Scholz U, Klaghofer R, Dux R, Roellin M, Boehler A, Muellhaupt B, et al. Predicting intentions and adherence behavior in the context of organ transplantation: gender differences of provided social support. J Psychosom Res. 2012;72:214–9.

    Article  PubMed  Google Scholar 

  60. Korb-Savoldelli V, Sabatier B, Gillaizeau F, Guillemain R, Prognon P, Bégué D, et al. Non-adherence with drug treatment after heart or lung transplantation in adults: a systematic review. Patient Educ Couns. 2010;81:148–54.

    Article  CAS  PubMed  Google Scholar 

  61. Favaro A, Gerosa G, Caforio ALP, Volpe B, Rupolo G, Zarneri D, et al. Posttraumatic stress disorder and depression in heart transplantation recipients: the relationship with outcome and adherence to medical treatment. Gen Hosp Psychiatry. 2011;33:1–7.

    Article  PubMed  Google Scholar 

  62. Denhaerynck K, Schmid-Mohler G, Kiss A, Steiger J, Wüthrich RP, Bock A, et al. Differences in Medication Adherence between Living and Deceased Donor Kidney Transplant Patients. Int J Organ Transplant Med. 2014;5:7–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Hatakeyama S, Fujita T, Yoneyama T, Yoneyama T, Koie T, Hashimoto Y, et al. A switch from conventional twice-daily tacrolimus to once-daily extended-release tacrolimus in stable kidney transplant recipients. Transplant Proc. 2012;44:121–3.

    Article  CAS  PubMed  Google Scholar 

  64. Kolonko A, Chudek J, Wiecek A. Improved kidney graft function after conversion from twice daily tacrolimus to a once daily prolonged-release formulation. Transplant Proc. 2011;43:2950–3.

    Article  CAS  PubMed  Google Scholar 

  65. Wlodarczyk Z, Squifflet J-P, Ostrowski M, Rigotti P, Stefoni S, Citterio F, et al. Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial. Am J Transplant. 2009;9:2505–13.

    Article  CAS  PubMed  Google Scholar 

  66. Shemesh E, Annunziato RA, Arnon R, Miloh T, Kerkar N. Adherence to medical recommendations and transition to adult services in pediatric transplant recipients. Curr Opin Organ Transplant. 2010;15:288–92.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Pascazio L, Nardone IB, Clarici A, Enzmann G, Grignetti M, Panzetta GO, et al. Anxiety, depression and emotional profile in renal transplant recipients and healthy subjects: a comparative study. Transplant Proc. 2010;42:3586–90.

    Article  CAS  PubMed  Google Scholar 

  68. Kadioglu ZO, Kacar S, Eroglu A, Guven B, Tilif S. Dyadic adjustment and psychological concordance of kidney transplant recipients and donors after spousal transplantation. Transplant Proc. 2012;44:1608–13.

    Article  CAS  PubMed  Google Scholar 

  69. Chisholm MA, Williamson GM, Lance CE, Mulloy LL. Predicting adherence to immunosuppressant therapy: a prospective analysis of the theory of planned behaviour. Nephrol Dial Transplant. 2007;22:2339–48.

    Article  CAS  PubMed  Google Scholar 

  70. Girerd X, Hanon O, Anagnostopoulos K, Ciupek C, Mourad JJ. Consoli S [Assessment of antihypertensive compliance using a self-administered questionnaire: development and use in a hypertension clinic]. Presse Med. 2001;30:1044–8.

    CAS  PubMed  Google Scholar 

  71. Ruiz MA, Pardo A, Rejas J, Soto J, Villasante F, Aranguren JL. Development and validation of the “Treatment Satisfaction with Medicines Questionnaire” (SATMED-Q). Value Health. 2008;11:913–26.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Alexandra Tavernier (M.A, University of Glasgow, UK; Professeur Agrégée, University of Lille, France) for reading and editing the manuscript.

Funding

No specific fundings were received.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephanie Belaiche.

Ethics declarations

Conflicts of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Belaiche, S., Décaudin, B., Dharancy, S. et al. Factors relevant to medication non-adherence in kidney transplant: a systematic review. Int J Clin Pharm 39, 582–593 (2017). https://doi.org/10.1007/s11096-017-0436-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-017-0436-4

Keywords

Navigation