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Changing Paradigms in the Management of Rejection in Kidney Transplantation: Evolving From Protocol-Based Care to the Era of P4 Medicine.

ABSTRACT: PURPOSE OF REVIEW:P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine's relevance to the various stages of the kidney transplant cycle. SOURCES OF INFORMATION:A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016) using a combination of subject headings (MeSH) and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine. The electronic database search was expanded further on particular subject headings. FINDINGS:Available histocompatibility methods exemplify current applications of the predictive and preventive domains of P4 medicine in kidney transplant recipients' care. Pharmacogenomics are discussed as means to facilitate personalized immunosuppression regimens and promotion of active patient participation as a means to improve adherence. LIMITATIONS:For simplicity, this review focuses on rejection. P4 medicine, however, should more broadly address health concerns in kidney transplant recipients, including competing outcomes such as infections, malignancies, and cardiovascular disease. This review highlights how biomarkers to evaluate these competing outcomes warrant validation and standardization prior to their incorporation into clinical practice. IMPLICATIONS:Consideration of all 4 domains of the P4 medicine framework when caring for and/or studying kidney transplant recipients has the potential of increasing therapeutic efficiency, minimizing adverse effects, decreasing health care costs, and maximizing wellness. Technologies to gauge immune competency, immunosuppression requirements, and early/reversible immune-mediated injuries are required to optimize kidney transplant care.

SUBMITTER: Maier M

PROVIDER: S-EPMC5308536 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Changing Paradigms in the Management of Rejection in Kidney Transplantation: Evolving From Protocol-Based Care to the Era of P4 Medicine.

Maier Mirela M Takano Tomoko T Sapir-Pichhadze Ruth R

Canadian journal of kidney health and disease 20170123

<h4>Purpose of review</h4>P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine's relevance to the various stages of the kidney transplant cycle.<h4>Sources of information</h4>A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016) using ...[more]

PMID: 28270929

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Project description:ImportanceAcute rejection is one of the most frequent complications in facial transplantation, with potentially severe consequences for the recipient if overlooked. Clinical signs, such as erythema or edema, are helpful to diagnose acute rejection in the early follow-up stage; however, it is not well known whether these clinical signs remain reliable markers of acute rejection beyond the second posttransplant year.ObjectiveTo determine the diagnostic value of clinical signs of acute rejection after facial transplantation over time.Design, setting, and participantsA retrospective, single-center cohort study was conducted of patients who underwent facial transplantation at Brigham and Women's Hospital between April 2009 and October 2014, with up to an 8-year follow-up. Medical records were reviewed until September 30, 2017. The medical records from 104 encounters with 7 patients who underwent partial or full facial transplantation were analyzed for symptoms of rejection, immunosuppressive therapy, and histopathologic findings.Main outcomes and measuresThe occurrence of 5 clinical signs of acute rejection were evaluated: erythema, edema, exanthema, suture line erythema, and mucosal lesions. Odds ratios (ORs) were calculated to determine the statistically significant association of these signs with the histopathologic diagnosis of rejection. In addition, tacrolimus blood levels, as a surrogate marker of immunosuppressive therapy, were evaluated.ResultsOf the 7 patients included in the study, 5 were men. The mean follow-up was 66 months (range, 35-101). Of 104 clinical encounters, 46 encounters (44.2%) represented rejection episodes and 58 encounters (55.8%) represented no-rejection episodes. Beyond 2 years posttransplantation, only erythema (OR, 6.53; 95% CI, 1.84-20.11; P = .004) and exanthema (OR, ∞; 95% CI, 2.2-∞; P = .004) were demonstrated to be reliable clinical signs of acute rejection in facial transplantation. There was also a statistically significant association of subtherapeutic tacrolimus levels with late rejection episodes (OR, 3.79; 95% CI, 1.25-12.88; P = .03). In addition, the occurrence of subclinical rejection was more frequent during later follow-up times (7 [24.1%] late rejections vs 1 [5.9%] early rejection). Five of 8 subclinical rejections (62.5%) were associated with subtherapeutic tacrolimus levels.Conclusions and relevanceClinical signs of acute rejection in facial transplantation appear to be of limited diagnostic value, particularly after the second postoperative year. Until alternative biomarkers for rejection are identified, protocol skin biopsies will remain necessary for guiding assessments of allograft rejection.Level of evidence3.

Project description:ObjectiveTo evaluate the clinical and laboratory characteristics in pregnancy that differentiate preeclampsia from acute renal allograft rejection and to investigate the maternal, neonatal, and graft sequelae of these diagnoses.MethodsWe conducted a retrospective case-controlled registry study of data abstracted from Transplant Pregnancy Registry International deliveries between 1968 and 2019. All adult kidney transplant recipients with singleton pregnancies of at least 20 weeks of gestation were included. Acute rejection was biopsy proven and preeclampsia was diagnosed based on contemporary criteria. Variables were compared using χ2, Fisher exact, and Wilcoxon rank sum tests as appropriate. Multivariable linear regression was used to analyze preterm birth. Kaplan-Meier curves with log-rank test and Cox proportional hazards model were used to compare graft loss over time.ResultsThere were 26 pregnant women with biopsy-confirmed acute rejection who were matched by the year they conceived to 78 pregnant women with preeclampsia. Recipients with acute rejection had elevated peripartum serum creatinine levels (73% vs 14%, P<.001), with median intrapartum creatinine of 3.90 compared with 1.15 mg/dL (P<.001). Conversely, only patients with preeclampsia had a significant increase in proteinuria from baseline. Although there were no significant differences in maternal outcomes, graft loss within 2 years postpartum (42% vs 10%) and long-term graft loss (73% vs 35%) were significantly increased in recipients who experienced acute rejection (P<.001 for both). The frequency of delivery before 32 weeks of gestation was 53% with acute rejection and 20% with preeclampsia. After controlling for hypertension and immunosuppressant use, acute rejection was associated with higher frequency of delivery at less than 32 weeks of gestation (adjusted odds ratio 4.04, 95% CI 1.10-15.2).ConclusionIn pregnancy, acute rejection is associated with higher creatinine levels, and preeclampsia is associated with increased proteinuria. Acute rejection in pregnancy carries a risk of prematurity and graft loss beyond that of preeclampsia for kidney transplant recipients.Funding sourceThe Transplant Pregnancy Registry International is supported in part by an educational grant from Veloxis Pharmaceuticals.

Dataset Information

Changing Paradigms in the Management of Rejection in Kidney Transplantation: Evolving From Protocol-Based Care to the Era of P4 Medicine.

Publications

Changing Paradigms in the Management of Rejection in Kidney Transplantation: Evolving From Protocol-Based Care to the Era of P4 Medicine.

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