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Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients.

ABSTRACT: Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18-question Center for Epidemiologic Studies-Depression Scale (CES-D). Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CES-D score > 14) and frailty were associated with KT length of stay (LOS), death-censored graft failure (DCGF), and mortality. At KT admission, 10.0% of patients exhibited depressive symptoms, 16.3% were frail, and 3.6% had both. Recipients with depressive symptoms were more likely to be frail (aOR = 3.97, 95% CI: 2.28-6.91, P < 0.001). Recipients with both depressive symptoms and frailty had a 1.88 times (95% CI: 1.70-2.08, P < 0.001) longer LOS, 6.20-fold (95% CI:1.67-22.95, P < 0.01) increased risk of DCGF, and 2.62-fold (95% CI:1.03-6.70, P = 0.04) increased risk of mortality, compared to those who were nonfrail and without depressive symptoms. There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction < 0.001). Interventions aimed at reducing pre-KT depressive symptoms and frailty should be explored for their impact on post-KT outcomes.

SUBMITTER: Konel JM

PROVIDER: S-EPMC6440201 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients.

Konel Jonathan M JM Warsame Fatima F Ying Hao H Haugen Christine E CE Mountford Alexandra A Chu Nadia M NM Crews Deidra C DC Desai Niraj M NM Garonzik-Wang Jacqueline M JM Walston Jeremy D JD Norman Silas P SP Segev Dorry L DL McAdams-DeMarco Mara A MA

Clinical transplantation 20180923 10

Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18-question Center for Epidemiologic Studies-Depression Scale (CES-D). Using adjusted Poisson regression and survival analysi ...[more]

PMID: 30152107

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Project description:Background:Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. Objective:To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. Design:Retrospective cohort study. Setting:We used linked health care databases in Alberta, Canada. Patients:We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. Measurements:The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ?0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. Methods:We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). Results:Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (-5.4 vs -1.9 mL/min/1.73 m2, P < .05). Limitations:We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. Conclusion:Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted.

Dataset Information

Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients.

Publications

Depressive symptoms, frailty, and adverse outcomes among kidney transplant recipients.

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