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Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.

ABSTRACT: Background:The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via "inflamm-aging." Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may have important implications for risk for adverse clinical outcomes. Methods:Three months after transplant, innate immune phenotype was evaluated by flow cytometry from 60 kidney transplant recipients (22 older [?60 years] and 38 younger [<60 years old]). Multiplex cytokine testing was used to evaluate plasma cytokine levels. Younger patients were matched to older patients based on transplant type and induction immune suppression. Results:Older kidney transplant recipients demonstrated decreased frequency of intermediate monocytes (CD14++CD16+) compared with younger patients (1.2% vs 3.3%, P = 0.007), and a trend toward increased frequency of proinflammatory classical monocytes (CD14++CD16-) (94.5% vs 92.1%) (P = 0.065). Increased levels of interferon-gamma (IFN-?) were seen in older patients. Conclusions:In this pilot study of kidney transplant recipients, we identified differences in the innate immune system in older as compared with younger patients, including increased levels of IFN-?. This suggests that age-associated nonspecific inflammation persists despite immune suppression. The ability to apply noninvasive testing to transplant recipients will provide tools for patient risk stratification and individualization of immune suppression regimens to improve outcomes after transplantation.

SUBMITTER: Liang EC

PROVIDER: S-EPMC5912018 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.

Liang Emily C EC Rossetti Maura M Sidwell Tiffany T Groysberg Victoria V Sunga Gema G Korin Yael Y Vangala Sitaram S Abdalla Basmah B Lum Erik E Bunnapradist Suphamai S Pham Phuong-Thu PT Danovitch Gabriel G Reed Elaine F EF Schaenman Joanna J

Transplantation direct 20180214 3

<h4>Background</h4>The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via "inflamm-aging." Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may ...[more]

PMID: 29707619

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Project description:Background Despite growing evidence focusing on health inequalities in older adults, inequalities in medical compensation compared with younger adults and gender disparities of medical errors among older patients have received little attention. This study aimed to disclose the aforementioned inequalities and examine the disparities in medical errors among older patients. Methods First, available litigation documents were searched on “China Judgment Online” using keywords including medical errors. Second, we compiled a database with 5,072 disputes. After using systematic random sampling to retain half of the data, we removed 549 unrelated cases. According to the age, we identified 424 and 1,563 cases related to older and younger patients, respectively. Then, we hired two frontline physicians to review the documents and independently judge the medical errors and specialties involved. A third physician further considered the divergent results. Finally, we compared the medical compensation between older and younger groups and medical errors and specialties among older patients. Results Older patients experienced different medical errors in divergent specialties. The medical error rate of male older patients was over 4% higher than that of females in the departments of general surgery and emergency. Female older patients were prone to adverse events in respiratory medicine departments and primary care institutes. The incidence of insufficient implementation of consent obligation among male older patients was 5.18% higher than that of females. However, females were more likely to suffer adverse events at the stages of diagnosis, therapy, and surgical operation. The total amount of medical compensation obtained by younger patients was 41.47% higher than that of older patients. Conclusions Except for the common medical errors and departments involved, additional attention should be paid to older patients of different genders according to the incidence of medical errors. Setting up the department of geriatrics or specialist hospitals is also an important alternative to improve patient safety for older people. Furthermore, there may be inequality in medical compensation in older patients due to the tort liability law of China.

Project description:Because extracellular vesicle (EV)-associated cytokines, both encapsulated and surface bound, have been associated with symptom severity, and may vary over the lifespan, they may be potential biomarkers to uncover underlying mechanisms of various conditions. This study evaluated the associations of soluble and EV-associated cytokine concentrations with distinct symptom profiles reported by 290 women with breast cancer prior to surgery. Patients were classified into older (≥60 years, n = 93) and younger (< 60 years, n = 197) cohorts within two previously identified distinct symptom severity profiles, that included pain, depressive symptoms, sleep disturbance, and fatigue (i.e., High Fatigue Low Pain and All Low). EVs were extracted using ExoQuick. Cytokine concentrations were determined using Luminex multiplex assay. Mann Whitney U test evaluated the differences in EV and soluble cytokine levels between symptom classes and between and within the older and younger cohorts adjusting for Karnofsky Performance Status (KPS) score, body mass index (BMI), and stage of disease. Partial correlation analyses were run between symptom severity scores and cytokine concentrations. Results of this study suggest that levels of cytokine concentrations differ between EV and soluble fractions. Several EV and soluble pro-inflammatory cytokines had positive associations with depressive symptoms and fatigue within both age cohorts and symptom profiles. In addition, in the older cohort with High Fatigue Low Pain symptom profile, EV GM-CSF concentrations were higher compared to the All Low symptom profile (p < 0.05). Albeit limited by a small sample size, these exploratory analyses provide new information on the association between cytokines and symptom profiles of older and younger cohorts. Of note, unique EV-associated cytokines were found in older patients and in specific symptom classes. These results suggest that EVs may be potential biomarker discovery tools. Understanding the mechanisms that underlie distinct symptom class profiles categorized by age may inform intervention trials and offer precision medicine approaches.

Project description:Background and objectivesOlder kidney transplant recipients are susceptible to cognitive impairment, frailty, comorbidities, immunosuppression-related complications, and chronic graft failure, however, there has been limited focus on their concerns and expectations related to transplantation. This study aims to describe the perspectives of older kidney transplant recipients about their experience of kidney transplantation, self-management, and treatment goals to inform strategies and interventions that address their specific needs.Design, setting, participants, & measurementsFace-to-face semistructured interviews were conducted with 30 kidney transplant recipients aged 65-80 years from five renal units in Australia. Transcripts were analyzed thematically.ResultsSix themes were identified: restoring vitality of youth (with subthemes of revived mindset for resilience, embracing enjoyment in life, drive for self-actualization); persisting through prolonged recovery (yielding to aging, accepting functional limitations, pushing the limit, enduring treatment responsibilities); imposing sicknesses (combatting devastating comorbidities, painful restrictions, emerging disillusionment, anxieties about accumulating side effects, consuming treatment burden); prioritizing graft survival (privileged with a miracle, negotiating risks for longevity, enacting a moral duty, preserving the last opportunity); confronting health deterioration (vulnerability and helplessness, narrowing focus to immediate concerns, uncertainty of survival); and value of existence (purpose through autonomy, refusing the burden of futile treatment, staying alive by all means).ConclusionsOlder kidney transplant recipients felt able to enjoy life and strived to live at their newly re-established potential and capability, which motivated them to protect their graft. However, some felt constrained by slow recuperation and overwhelmed by unexpected comorbidities, medication-related side effects, and health decline. Our findings suggest the need to prepare and support older recipients for self-management responsibilities, clarify their expectations of post-transplant risks and outcomes, and provide assistance through prolonged recovery after kidney transplantation.

Dataset Information

Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.

Publications

Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.

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