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

Mathilde Prezelin-Reydit,Benoît Barrou,Christophe Mariat,Anne Parissiadis,Virginie Renac,Pierre Merville,Valérie Dubois,Isabelle Etienne,Françoise Hau,Lionel Couzi,Monique Pourtein,Cécile Vigneau,Léna Absi,Jean-Luc Taupin,Gwendaline Guidicelli,Olivier Thaunat,Laetitia Albano,Sophie Caillard,Jonathan Visentin

doi:10.3390/jcm10092032

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.

Highlights

Despite the use of potent oral immunosuppressants, an alloimmune response directed against the donor is the dominant cause of kidney graft failure (GF)
To assess the effect of medication non-adherence (MNA) on each outcome, we evaluated MNA according to the adherence status at each time of measure and the global Morisky score at the four visits
After testing different calcineurin inhibitor (CNI) trough levels, we found that patients with tacrolimus trough levels below 5 ng/mL and cyclosporine trough levels below 100 ng/mL at 24 months post-transplant had a probability to survive with a functioning graft for ≥5 years post-KT of 76.1% vs. 95.1% for patients with tacrolimus trough levels above

Summary

Introduction

Despite the use of potent oral immunosuppressants, an alloimmune response directed against the donor is the dominant cause of kidney graft failure (GF). This response involves both T cells with borderline and T-cell-mediated rejection (TCMR) and donor-specific antibodies (DSA), which lead to antibody-mediated rejection (ABMR) [1,2]. 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). MNA was assessed prospectively at 3, 6, 12, and 24 months (M) post-KT, using the Morisky scale. Results: The initial percentage of MNA patients was 17.7%, increasing to 34.6% at 24 months

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