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

Jeffrey J Gaynor,George W Burke,Lissett Moni,David Roth,Mariella Ortigosa-Goggins,Warren Kupin,Linda Chen,Giselle Guerra,Marina M Tabbara,Adela Mattiazzi,Gaetano Ciancio

doi:10.3390/jcm11051334

Jeffrey J Gaynor, George W Burke + Show 9 more

Open Access

https://doi.org/10.3390/jcm11051334

Copy DOI

Abstract

Background: We previously reported that graft failure due to nonadherence (GFNA) was a major cause of graft loss in kidney transplantation. Here, among 150 prospectively-followed kidney transplant recipients at 18 years post-transplant, we provide: updated (longer-term) estimates of cause-specific graft loss probabilities, risk factors for developing GFNA, and detailed characterizations of patients’ overt nonadherent (NA) behavior, including timing, extent, and clinical consequences. Methods: Determination of the patient becoming NA in taking his/her immunosuppressive medications, and the underlying cause of graft loss, were determined prospectively by the attending physicians. For never-functioning-graft, GFNA, GF due to causes other than NA (Other GF), and death with a functioning graft (DWFG), cumulative incidence functions were used to estimate the cumulative probabilities of cause-specific graft loss. Cox stepwise regression was used to determine significant multivariable predictors for the hazard rate of developing GFNA. Results: GFNA was a major cause of graft loss (22/150 patients), particularly among African-American and Hispanic recipients <50 years of age-at-transplant (20/56 experienced GFNA), with estimated percentages of such patients ever developing GFNA ranging between 36.9 and 41.5%. These patients were also at a higher risk of developing Other GF. For the remaining patients (2/94 experienced GFNA), estimated percentages of ever-developing GFNA were much lower (range: 0.0–6.7%). The major cause of graft loss among recipients ≥50 years of age was DWFG; GFNA rarely occurred among older recipients. In 21/22 GFNA patients, NA behavior lasted continuously from the time of developing NA until GFNA. In total, 28/150 patients became NA, and 67.9% (19/28) occurred beyond 36 months post-transplant. A total of 25 of 28 NA patients (89.3%) developed biopsy-proven acute rejection and/or chronic rejection that was directly attributed to the NA behavior. Lastly, 25/28 admitted to NA behavior, with financial and psychological components documented in 71.4% (20/28) and 96.4% (27/28) of NA cases, respectively. Conclusions: These results highlight the importance of performing serial monitoring of patients for overt NA behavior throughout their post-transplant follow-up. Financial and psychological components to NA behavior need to be simultaneously addressed with the goal of achieving complete avoidance/elimination of NA behavior among higher risk patients.

Highlights

insurance issues (Ins) 2014, we reported that graft failure due to nonadherence (GFNA) was a major cause of graft loss among 628 adult primary kidney transplant recipients, having a median follow-up of 56 months post-transplant [1], results that were consistent with a number of other reports [2–10]
We recently reported the results at 18 years post-transplants for the 150 study participants in the first trial [11], which included 10 additional years of patient follow-up compared with our previous reports [1,12]
It is relatively rare for longer-term estimates of cause-specific graft loss following kidney transplantation to be reported, clinical trial results occurring beyond 8–10 years post-transplant

Summary

Introduction

In 2014, we reported that graft failure due to nonadherence (GFNA) (nonadherence being defined as the patient either abruptly stopping or consistently not taking the prescribed immunosuppressive medications) was a major cause of graft loss among 628 adult primary kidney transplant recipients, having a median follow-up of 56 months post-transplant [1], results that were consistent with a number of other (mostly older) reports [2–10]. Rosenberger et al [15] defined “major noncompliance” as “the situation when a patient dramatically violates the immunosuppressive regime with following rejection episode and graft loss as a consequence,” and Dunn et al [9] defined “overt nonadherence” as the patient “admitting to not taking the immunosuppressive medications for a prolonged period of time.”. These more overt definitions of NA behavior are similar to those used in previous reports and by our center [1–8,10]. In terms of those patients who became overtly NA, Dunn et al [9]

Methods

Results

Discussion

Conclusion