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

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.

Developing Clinical Prognostic Models to Predict Graft Survival after Renal Transplantation: Comparison of Statistical and Machine Learning Models

“…This result indicates that nonadherence is a significant risk factor for graft failure and it associated with poor graft survival. This finding is well supported by the literature [33][34][35]. Patient education, counseling, and support systems are crucial in promoting adherence to immunosuppressive medications and post-transplant care, thereby improving graft survival.…”

Competing Risks Analysis of Kidney Transplant Waitlist Outcomes: Two Important Statistical Perspectives

“…For example, in adult kidney transplantation, we recently reported that the estimated cumulative incidences of graft loss due to overt nonadherence and graft loss without overt nonadherence were 0.288 and 0.443 at 18 years posttransplant, respectively, among 82 patients who were aged <50 years at transplant. 28 Overall graft survival at 18 years posttransplant was estimated for this subgroup to be 0.269 (1.00 – [0.288 + 0.443]). A clinician might therefore want to suggest to a newly transplanted recipient aged <50 years that conditional on his or her not previously experiencing graft loss due to overt nonadherence (i.e., avoiding overt nonadherence), graft survival at 18 years posttransplant would be estimated to improve to 0.378, that is, 0.269 / (1.0 − 0.288).…”

Application of self-reporting, clinicians’ assessment, and tacrolimus trough levels in evaluating adherence to immunosuppressive therapy in kidney transplant recipients. A cohort study

“…(11) Evidence shows a gradual decline in adherence with prolonged length of posttransplant duration, resulting in a higher incidence of late acute rejection among nonadherence. (12,13) Like in any other condition, medication nonadherence in KTRs increases with the number of medications prescribed. (14) Social support plays a role in the adherence rate, with married people showing higher levels of adherence than single individuals.…”