Graft Failure Due to Noncompliance Among 628 Kidney Transplant Recipients With Long-term Follow-up

Gaynor, Jeffrey J.; Ciancio, Gaetano; Guerra, Giselle; Sageshima, Junichiro; Hanson, Lois; Roth, David; Chen, Linda; Kupin, Warren; Mattiazzi, Adela; Tueros, Lissett; Flores, Sandra; Aminsharifi, Jason; Joshi, Shivam; Chediak, Zoila; Ruiz, Phillip; Vianna, Rodrigo; Burke, George W.

doi:10.1097/01.tp.0000438199.76531.4a

Cited by 67 publications

(65 citation statements)

References 46 publications

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“…Since non-adherence can contribute to AR and graft loss (24), we systematically evaluated patient charts and levels of immunosuppressive drugs at the time of for-cause biopsy and identified only 5 patients whose rejection episodes were associated with insufficient immunosuppression (2 in DSA positive group secondary to patient non-adherence and 3 in DSA negative group secondary to BKV infection; SDC Methods). SDC Figure S2 demonstrates that tacrolimus trough levels and MMF dose at the time of for-cause biopsies were not statistically different between those with and without AR.…”

Section: Resultsmentioning

confidence: 99%

Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure

et al. 2015

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Background Characteristics of pretransplant antibodies directed at donor HLA (DSA) associated with adverse outcomes in kidney transplant recipients are being elucidated but uncertainties exist. Methods Prospectively screening of pretransplant sera from 543 kidney recipients using single antigen bead assays identified 154 recipients with DSA and 389 without. We investigated the association of DSA features to acute rejection (AR) and graft failure. Results One-year AR incidence was higher in DSA positive group (P<0.001), primarily due to antibody mediated rejection (AMR, 13% vs. 1.8%, P<0.001) and not T-cell mediated rejection (ACR, 5% vs.6%, P=0.65). Risk of AMR increased progressively with a rise in DSA MFI-Sum (P<0.0001). Both DSA MFI-Sum ≥6000 (OR=18; 95%CI, 7.0 to 47; P<0.001) and DSA specificity, presence of DSA against both HLA class I and II (OR=39; 95%CI, 14 to 106; P<0.0001), predicted one-year AMR, independent of other covariates. In a combined model, DSA specificity predicted AMR, independent of DSA MFI-Sum. In multivariable Cox proportional hazards models, the covariate-adjusted hazard ratio for graft failure was 2.03 (95%CI, 1.05 to 3.92; P=0.04) for DSA MFI-Sum≥6000 and 2.23 (95% CI, 1.04 to 4.80; P=0.04) for class I and II DSA. Prediction of graft loss was not independent of AMR. Conclusions Our study supports the hypothesis that characterization of pretransplant DSA, specifically presence of DSA against both HLA class I and II and the strength, as quantified by DSA MFI-Sum, is useful to estimate AMR and graft failure risk in kidney graft recipients. Elevated risk of graft failure is attributable to increased risk of AMR.

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Section: Resultsmentioning

confidence: 99%

Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure

et al. 2015

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“…A small single center study of pediatric heart transplant recipients undergoing transition to adult care showed a higher risk of death among older adolescents and young adults than other age groups; it was not clear if this study adjusted for time since transplant (39). Previous work in the kidney transplant population suggested that irrespective of time since transplant, emerging adults (age [17][18][19][20][21][22][23][24] have the highest risk of graft failure (13). The present study demonstrates that a similar relationship exists in heart transplant recipients, with graft failure rates peaking at 21-24 years old, regardless of time since transplant.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging adulthood is defined as the interval between late adolescence and approximately 25 years of age (15). Many believe that nonadherence to immunosuppressive therapy is the most important factor contributing to poor graft survival among kidney transplant recipients in emerging adulthood (16)(17)(18)(19); poor adherence has been more commonly reported in emerging adults than any other age group (17,20,21). In both pediatric and adult heart recipients, poor adherence has been associated with both late acute rejection and death (22)(23)(24)(25); similar associations between adherence and outcomes have also been observed in other organ types (17,20,21,(26)(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

High Risk of Graft Failure in Emerging Adult Heart Transplant Recipients

Foster

Dahhou

Zhang

et al. 2015

American Journal of Transplantation

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Emerging adulthood (17-24 years) is a period of high risk for graft failure in kidney transplant. Whether a similar association exists in heart transplant recipients is unknown. We sought to estimate the relative hazards of graft failure at different current ages, compared with patients between 20 and 24 years old. We evaluated 11 473 patients recorded in the Scientific Registry of Transplant Recipients who received a first transplant at <40 years old and had at least 6 months of graft function. Timedependent Cox models were used to estimate the association between current age (time-dependent) and failure risk, adjusted for time since transplant and other potential confounders. Failure was defined as death following graft failure or retransplant; observation was censored at death with graft function. There were 2567 failures. Crude age-specific graft failure rates were highest in 21-24 year olds (4.2 per 100 person-years). Compared to individuals with the same time since transplant, 21-24 year olds had significantly higher failure rates than all other age periods except 17-20 years (HR 0.92 [95%CI 0.77, 1.09]) and 25-29 years (0.86 [0.73, 1.03]). Among young first heart transplant recipients, graft failure risks are highest in the period from 17 to 29 years of age.Abbreviations: HLA, human leukocyte antigen; HR, hazard ratio; IQR, interquartile range; SES, socioeconomic status; SRTR, Scientific Registry of Transplant Recipients

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“…Early medication adherence 3-months post renal transplantation varies between 93.5% and 84% depending on the complexity of the immunosuppressant treatment (from once-daily regimen to 4 doses per day) 20. Immunosuppressant medication nonadherence, which is partly influenced by psychosocial determinants, is an important trigger of acute rejection and graft loss in solid-organ transplant (SOT) recipients 19,21,22. Nonadherence contributes to 20% of late acute rejection episodes and 16% of graft losses in kidney transplantation 19.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

Michaud¹,

Ludwig²,

Berney³

et al. 2016

Pharm Pract (Granada)

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Background:Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT) recipients.Objective:This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20) might have lower medication adherence than noncomplex patients (INTERMED≤20).Methods:Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20).Results:Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11) and noncomplex patients (N=21) were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value). Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study.Conclusion:Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly morbid patients who have complex social and psychological characteristics.

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Graft Failure Due to Noncompliance Among 628 Kidney Transplant Recipients With Long-term Follow-up

Abstract: GFNC is a major cause of late GF at our center, with younger and non-white recipients at a significantly greater GFNC risk. Interventional approaches to eliminate GFNC could dramatically improve long-term kidney graft survival.

Cited by 67 publications

References 46 publications

Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure

Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure

High Risk of Graft Failure in Emerging Adult Heart Transplant Recipients

Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

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