Prospective Measures of Adherence by Questionnaire, Low Immunosuppression and Graft Outcome in Kidney Transplantation

Abstract

Background: Non-adherence with immunosuppressant medication (MNA) fosters development of de novo donor-specific antibodies (dnDSA), rejection, and graft failure (GF) in kidney transplant recipients (KTRs). However, there is no simple tool to assess MNA, prospectively. The goal was to monitor MNA and analyze its predictive value for dnDSA generation, acute rejection and GF. Methods: We enrolled 301 KTRs in a multicentric French study. MNA was assessed prospectively at 3, 6, 12, and 24 months (M) post-KT, using the Morisky scale. We investigated the association between MNA and occurrence of dnDSA at year 2 post transplantation, using logistic regression models and the association between MNA and rejection or graft failure, using Cox multivariable models. Results: The initial percentage of MNA patients was 17.7%, increasing to 34.6% at 24 months. Nineteen patients (8.4%) developed dnDSA 2 to 3 years after KT. After adjustment for recipient age, HLA sensitization, HLA mismatches, and maintenance treatment, MNA was associated neither with dnDSA occurrence, nor acute rejection. Only cyclosporine use and calcineurin inhibitor (CNI) withdrawal were strongly associated with dnDSA and rejection. With a median follow-up of 8.9 years, GF occurred in 87 patients (29.0%). After adjustment for recipient and donor age, CNI trough level, dnDSA, and rejection, MNA was not associated with GF. The only parameters associated with GF were dnDSA occurrence, and acute rejection. Conclusions: Prospective serial monitoring of MNA using the Morisky scale does not predict dnDSA occurrence, rejection or GF in KTRs. In contrast, cyclosporine and CNI withdrawal induce dnDSA and rejection, which lead to GF.

Graft Failure Due to Nonadherence among 150 Prospectively-Followed Kidney Transplant Recipients at 18 Years Post-transplant: Our Results and Review of the Literature

“…As stated in the Introduction, many studies [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ] have analyzed patient self-reporting results by focusing on “whether any immunosuppression-taking NA has occurred” (with “no” implying perfect adherence). In fact, the ordinal scale portion of the self-reporting questionnaire (BAASIS, ITAS, Morisky, or some other), which attempts to measure the extent of a patient’s NA behavior, has often not been more fully utilized.…”

“…Furthermore, in some of these NA studies, the self-reporting questionnaire was only given to patients during the first 12–24 months post-transplant, and this study along with previous reports [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ] have shown that both NA and GFNA are more likely to occur late, i.e., beyond 24 months, in the patient’s post-transplant follow-up. While use of a patient self-reporting questionnaire, as highlighted in these studies, [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ] provides a simple snapshot of patient NA behavior, usually within the most recent 4 weeks (range: 1 week–3 months), achieving an accurate picture of each patient’s NA behavior over time would most likely require serial use of patient self-reporting throughout post-transplant follow-up.…”

“…Many reports of patient nonadherence (NA) in the literature have focused on analyzing the results of patient self-reporting using the strict dichotomy, “whether any immunosuppression-taking NA has occurred”, with “no” implying perfect adherence, and “yes” implying any evidence of nonadherent (NA) behavior [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. The main problem with using such a strict dichotomy of “perfect adherence” vs. “any type of NA behavior” is the fact that this NA definition includes all levels of minor/subclinical NA behavior, including patients who (to a small degree) mistime their dose-taking, take less than the prescribed dose, and/or even skip taking some doses.…”

Measurement of the Immunosuppressant Possession Ratio by Transplant Clinical Pharmacists Captures a Non-Adherence Associated With Antibody-Mediated Rejection

“…Suspicion by the clinician of medication non-adherence underestimates this phenomenon and is frequently influenced by a poor outcome or non-adherence to follow-up [18]. Self-reported measurement of medication non-adherence is easily distorted by patients, explaining why its ability to predict rejection and graft loss is equivocal [19][20][21][22][23]. Objective methods for the measurement of non-adherence include calcineurin inhibitor trough levels and electronic monitoring.…”