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American Journal of Transplantation :... Nov 2009The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is...
The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression, graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially on the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.
Topics: Cardiovascular Diseases; Evidence-Based Practice; Global Health; Graft Rejection; Humans; Immunosuppression Therapy; Infection Control; Kidney Failure, Chronic; Kidney Transplantation; Neoplasms; Outcome Assessment, Health Care
PubMed: 19845597
DOI: 10.1111/j.1600-6143.2009.02834.x -
EBioMedicine Dec 2022Sepsis is an ill-defined syndrome yet is a leading cause of morbidity and mortality worldwide. The most recent consensus defines sepsis as life-threatening organ... (Review)
Review
Sepsis is an ill-defined syndrome yet is a leading cause of morbidity and mortality worldwide. The most recent consensus defines sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. However, this definition belies the complexity and breadth of immune mechanisms involved in sepsis, which are characterized by simultaneous hyperinflammation and immune suppression. In this review, we describe the immunopathogenesis of sepsis and highlight some recent pathophysiological findings that have expanded our understanding of sepsis. Sepsis endotypes can be used to divide sepsis patients in different groups with distinct immune profiles and outcomes. We also summarize evidence on the role of the gut microbiome in sepsis immunity. The challenge of the coming years will be to translate our increasing knowledge about the molecular mechanisms underlying sepsis into therapies that improve relevant patient outcomes.
Topics: Humans; Sepsis; Immunosuppression Therapy; Gastrointestinal Microbiome
PubMed: 36470832
DOI: 10.1016/j.ebiom.2022.104363 -
Clinical Infectious Diseases : An... Oct 2021Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for... (Review)
Review
Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The "net state of immune suppression" is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual's ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections; thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.
Topics: Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Organ Transplantation
PubMed: 32803228
DOI: 10.1093/cid/ciaa1189 -
Blood Jan 2015Chronic graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The... (Review)
Review
Chronic graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT). The 2-year cumulative incidence of chronic GVHD requiring systemic treatment is ~30% to 40% by National Institutes of Health criteria. The risk of chronic GVHD is higher and the duration of treatment is longer after HCT with mobilized blood cells than with marrow cells. Clinical manifestations can impair activities of daily living and often linger for years. Hematology and oncology specialists who refer patients to centers for HCT are often subsequently involved in the management of chronic GVHD when patients return to their care after HCT. Treatment of these patients can be optimized under shared care arrangements that enable referring physicians to manage long-term administration of immunosuppressive medications and supportive care with guidance from transplant center experts. Keys to successful collaborative management include early recognition in making the diagnosis of chronic GVHD, comprehensive evaluation at the onset and periodically during the course of the disease, prompt institution of systemic and topical treatment, appropriate monitoring of the response, calibration of treatment intensity over time in order to avoid overtreatment or undertreatment, and the use of supportive care to prevent complications and disability.
Topics: Allografts; Chronic Disease; Female; Graft vs Host Disease; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Incidence; Male
PubMed: 25398933
DOI: 10.1182/blood-2014-08-551994 -
Blood Mar 2017Acquired severe aplastic anemia (SAA) is a rare hematologic disease associated with significant morbidity and mortality. Immune destruction of hemopoietic stem cells... (Review)
Review
Acquired severe aplastic anemia (SAA) is a rare hematologic disease associated with significant morbidity and mortality. Immune destruction of hemopoietic stem cells plays an important role in pathogenesis, as shown by successful treatment with immunosuppressive agents, leading to transfusion independence or complete recovery of peripheral blood counts in a proportion of patients. Growth factors can be combined with immunosuppressive therapy (IST) and may improve response rates, as recently shown with thrombopoietin analogs. Anabolic steroids may still play a role in combination with IST. The problem with IST is failure to respond and the development of late clonal disorders. Bone marrow transplantation (BMT) is the other therapeutic option: a matched sibling donor remains the best choice. For patients lacking a matched family donor, unrelated donors can be readily found, although mostly for patients of Caucasian origin. Other BMT options include unrelated cord blood or mismatched family donors. Acute and chronic graft-versus-host disease remain important complications of BMT. Patient age is a strong predictor of outcome for both IST and BMT, and must be considered when designing therapeutic strategies. Early diagnosis and treatment, as well as long-term monitoring, remain crucial steps for successful treatment of SAA.
Topics: Anemia, Aplastic; Bone Marrow Transplantation; Humans; Immunosuppression Therapy; Treatment Outcome
PubMed: 28096088
DOI: 10.1182/blood-2016-08-693481 -
Clinical Microbiology Reviews Jun 2020The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as... (Review)
Review
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
Topics: Biological Products; Humans; Immunomodulation; Immunosuppression Therapy; Opportunistic Infections; Risk Factors
PubMed: 32522746
DOI: 10.1128/CMR.00035-19 -
Ophthalmology Feb 2018The uveitides are a collection of more than 30 diseases characterized by intraocular inflammation. Many cases of juvenile idiopathic arthritis-associated uveitis, many... (Review)
Review
The uveitides are a collection of more than 30 diseases characterized by intraocular inflammation. Many cases of juvenile idiopathic arthritis-associated uveitis, many cases of intermediate uveitis, and most cases of posterior and panuveitides requiring treatment are treated with corticosteroids and immunosuppression. Disease-specific, time-updated modeling of clinical data for several uveitides suggests superior prevention of ocular complications and visual outcomes with immunosuppression. These studies also suggest that oral corticosteroids at doses low enough for safe long-term therapy (i.e., <7.5 mg/day) are ineffective, implying that immunosuppression should be part of the initial regimen. The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study was a randomized comparative effectiveness trial comparing systemic therapy with oral corticosteroids and immunosuppression with regional corticosteroid treatment. It demonstrated that, when used properly, oral corticosteroids and immunosuppression can be given safely for up to 7 years with no evident increased risk of systemic side effects compared with regional corticosteroid therapy, except for greater antibiotic use for infections. The Systemic Treatment for Eye Diseases (SITE) Cohort Study suggested long-term safety for this approach, when the immunosuppressive agents were antimetabolites or calcineurin inhibitors. Thus, oral corticosteroids and immunosuppression may be a preferred initial therapy for many noninfectious, intermediate, posterior, and panuveitides. Nonalkylating-agent immunosuppression has a low rate of sustained, drug-free remissions, <10%/year. Nonalkylating-agent immunosuppression for >3 years with control of the inflammation for >2 years is associated with a decreased risk of relapse after discontinuing immunosuppression. Alkylating agents can induce sustained drug-free remissions but likely increase the lifetime risk of cancer. Biologics, which target specific cytokines and pathways, hold promise for the future. Monoclonal antibodies directed against tumor necrosis factor (TNF)-α have been studied most often, and one, adalimumab, is U.S. Food and Drug Administration approved for the treatment of noninfectious, intermediate, posterior, and panuveitides.
Topics: Humans; Immunosuppression Therapy; Immunosuppressive Agents; Uveitis; Visual Acuity
PubMed: 28942074
DOI: 10.1016/j.ophtha.2017.08.007 -
Clinical Journal of the American... Dec 2021Cardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several...
Cardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus; Risk Factors; Kidney Transplantation; Immunosuppression Therapy
PubMed: 34556500
DOI: 10.2215/CJN.00520121 -
Lancet (London, England) May 2009Since the introduction of pancreas transplantation more than 40 years ago, efforts to develop more minimally invasive techniques for endocrine replacement therapy have... (Review)
Review
Since the introduction of pancreas transplantation more than 40 years ago, efforts to develop more minimally invasive techniques for endocrine replacement therapy have been in progress, yet this surgical procedure still remains the treatment of choice for diabetic patients with end-stage renal failure. Many improvements have been made in the surgical techniques and immunosuppressive regimens, both of which have contributed to an increasing number of indications for pancreas transplantation. This operation can be justified on the basis that patients replace daily injections of insulin with an improved quality of life but at the expense of a major surgical procedure and lifelong immunosuppression. The various indications, categories, and outcomes of patients having a pancreas transplant are discussed, particularly with reference to the effect on long-term diabetic complications.
Topics: Coronary Disease; Diabetes Complications; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Morbidity; Pancreas Transplantation; Patient Selection; Quality of Life; Survival Rate; Tissue and Organ Procurement; Transplantation Immunology; Treatment Outcome
PubMed: 19465236
DOI: 10.1016/S0140-6736(09)60609-7 -
Hematology/oncology and Stem Cell... Dec 2017Allotransplantation cures patients by cytoreduction and the graft-versus-tumor (leukemia; graft-versus-leukemia [GVL]) alloresponse; both eliminate residual disease. The... (Review)
Review
Allotransplantation cures patients by cytoreduction and the graft-versus-tumor (leukemia; graft-versus-leukemia [GVL]) alloresponse; both eliminate residual disease. The spectrum of conditioning intensity influences toxicities and non-relapse mortality. The spectrum of tumor sensitivity to the GVL response influences relapse. Balancing tolerable toxicities (influenced by patients' performance status and comorbidities) is also influenced by the graft. Intense immunosuppression (for engraftment and graft-versus-host disease prevention) may constrain the immunologic potency of the graft and limit the antineoplastic capacity of the transplant, thus requiring more intense or more effective conditioning regimens to limit the risks of relapse and permit satisfactory disease-free survival.
Topics: Allografts; Graft Survival; Graft vs Host Disease; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Neoplasms; Transplantation Conditioning
PubMed: 28641099
DOI: 10.1016/j.hemonc.2017.05.002