Post-transplantation diabetes mellitus

Post-transplantation diabetes mellitus (PTDM) is defined as sustained hyperglycemia developing in any patient without history of diabetes before transplantation, that meets the current diagnostic criteria by the American Diabetes Association or the World Health Organization. Several risk factors have been identified: age, nonwhite ethnicity, and glucocorticoid therapy for rejection and chronic immunosuppression with cyclosporine and especially tacrolimus. The pathophysiology of this condition resembles that of type 2 diabetes mellitus: pretransplantation end-stage liver/renal and heart disease are insulin-resistant states, and after transplantation, glucocorticoids induce further peripheral insulin insensitivity. The "second hit" appears to be an acquired (yet reversible) insulin secretion defect resulting from the calcineurin inhibitors cyclosporine and tacrolimus. An international panel of experts has recently published the proceeding of a Consensus Conference proposing strategies for the screening, prevention and management of PTDM. Future directions include pre- and post-transplantation glucose load testing for high-risk individuals and pharmacological agents to decrease insulin resistance and to preserve beta-cell function.     

Post-transplantation T cell lymphoblastic lymphoma

Immunosuppressed renal transplant recipients are at increased risk for large cell lymphoma of B cell phenotype. This report describes a case of post-transplantation lymphoma presenting with a mediastinal mass causing superior vena cava syndrome, tracheal obstruction, and pleural effusion. Cytospin preparations of pleural fluid documented high-grade lymphoblastic lymphoma morphology and immature T cell (cortical thymocyte) phenotype: Leu 1-6-positive, Leu 9-positive, Tdt-positive, B-negative, Calla-positive. The occurrence of post-transplantation lymphoma of T cell lineage is inconsistent with the postulated Epstein-Barr virus origin and raises important questions regarding the development of lymphoproliferative disorders in immunosuppressed organ transplant recipients.     

Post-transplantation Development of Food Allergies

Purpose of Review

The development of food allergies is increasingly being recognized as a post-solid organ transplant complication. In this article, we review the spectrum of post-transplant food allergy development and the proposed mechanisms for de novo food allergies and the clinical significance they pose.

Recent Findings

The development of new food allergies is disproportionately associated with pediatric liver transplants, where it occurs in up to 38% of select populations. The mechanism of food allergy development is not completely understood; however, it is likely promoted by unbalanced immune suppression.

Summary

De novo food allergy development is a common complication of solid organ transplants with the highest risk occurring in pediatric liver transplant recipients. There are likely multiple mechanisms for food allergy development including passive transfer of membrane-bound IgE and lymphocytes from donor to recipient, as well as loss of food tolerance and active development of new food allergies. The optimal management of food allergies following organ transplants has not been well researched but may include changing the immune suppression regimen if the food allergy does not resolve without intervention.

     

Post-transplantation lymphoproliferative disorder in pediatric patient

Immunosuppressive therapy for transplanted patients exposes them to a high risk of developing posttransplantation lymphoproliferative disorders (PTLD). We report the case of a child undergoing heart transplantation at seven months of age who developed PTLD at nine years of age, diagnosed by resection of a pulmonary nodule.     

肾移植术后糖尿病相关危险因素

目的:了解肾移植受者移植术后新发糖尿病(PTDM)的发病率,并筛选可能相关的危险因素,为制定移植术后个体化治疗方案提供依据。方法:收集自2007年10月至2011年4月于四川省人民医院器官移植中心行同种异体肾移植术受者的临床资料,共155例,男性108例、女性47例。根据本研究采用的PTDM诊断标准及定义,共有128例纳入本研究,将其分为PTDM组(51例)和非PTDM组(77例)。收集资料包括:肾移植术前年龄、体质量指数(BMI)、烟酒史、家族史、胆固醇、三酰甘油、血压、尿酸、有无透析治疗、透析时间,术后免疫抑制剂方案和术后急性排斥反应发生等。结果:我院PTDM的发病率为39.84%。两组患者术前在年龄、性别、BMI、血压、血脂、血尿酸等方面无统计学差异(P0.05)。单因素Logistic回归分析示:患者术前年龄、性别、BMI、血压、血脂、血尿酸等因素与PTDM的发生无相关性(P0.05);是否透析及透析时间与PTDMD的发生也无相关性(P0.05);FK506免疫方案组及术后发生急性排斥反应与PTDM的发生的呈明显相关性(P0.05)。将各变量再纳入多因素非条件Logistic逐步回归,显示他克莫司(FK506)免疫方案组及术后发生急性排斥反应与PTDM的发生呈明显相关性(P0.05)。结论:术前是否透析和透析时间与PTDM的发生无相关性;术后使用FK506免疫方案组和术后发生急性排斥反应则是PTDM发生的独立危险因素。     

Post-transplantation lymphoproliferation in patients with intensive immunosuppression

Organ allograft recipients are at higher risk for malignancies development. This risk is known to be different in different types of tumours. Skin cancers and lymphoproliferative disorders have been described to be ones the most frequent (comprising 15-25% of all malignancies). Here, we present the case of expansive formation localized near the renal allograft in patient, whose native kidneys failed as a consequence of long-term cyclosporine A therapy after orthotopic heart transplantation. The maintenance immunosuppression consisted of combination of cyclosporine A, mycophenolate mofetil and steroids. The expansion offside of transplanted kidney was detected by routine ultrasound examination. After indifferent neurological symptoms, sepsis, and then multiorgan failure occured. Shortly after acute surgery patient died. Autopsy and histopathology showed lymphoproliferative disorder--mo- nomorphic type of posttransplant lymphoproliferative disorder (PTLD). Occurence of PTLD in organ transplantation is discussed.     

Glucocorticoid-induced osteoporosis.

Glucocorticoid drugs interact with bone metabolism at many levels, but their principal action is to reduce osteoblast number and bone matrix synthesis. Virtually all patients receiving glucocorticoids in doses above 5 mg per day lose bone, the amount lost being dependent on the cumulative steroid dose. The risk of fracture is also related to the individual's initial bone density, which in turn reflects race, sex, age, menopausal status, body weight, smoking and the nature of any underlying illness. Bone density measurement and personal fracture history are the best predictors of future fracture risk. Steroid-induced bone loss is reversible, so measures to minimize the systemic steroid dose or to withdraw these drugs altogether should be pursued no matter how long an individual has been using them. Increasing the calcium intake to 1.5 g per day, encouraging them to stop smoking and take more exercise, and treating any vitamin D deficiency are sensible measures in all patients. In those at high risk, bisphosphonates are the best documented interventions, although sex hormone replacement is also effective and can be used alone or in addition to bisphosphonates.     

Secondary osteoporosis.

Bone loss occurs during the normal aging process. The term "primary" osteoporosis refers to osteoporosis that results from the involutional losses associated with aging and, in women, additional losses related to natural menopause. Osteoporosis that is caused or exacerbated by other disorders or medication exposures is referred to as "secondary" osteoporosis. This article describes the major causes and provides a framework for the diagnostic investigation of patients with suspected of having secondary osteoporosis.     

Glucocorticoid-induced osteoporosis.

Endogenous cortisol excess and glucocorticoid (GC) treatment have a profound effect on bone metabolism, acting at many sites. The mechanism of GC action on bone turnover is complex and has not been elucidated completely. GCs increase bone resorption, inhibit bone formation and have an indirect action on bone by decreasing intestinal Ca2+ absorption, modifying vitamin D metabolism, and sustaining a marked hypercalciuria, with variable changes in plasma PTH levels; finally, GCs inhibit the gonadotropic and somatotropic axis. GC-induced osteoporosis is preventable, treatable and potentially reversible. The prevention and treatment of GC-induced osteoporosis include some general measures (as well as the use of the minimal effective dose of GC), Ca2+ and vitamin D supplementation and treatment with bone anabolic and antiresorptive agents. Recent trials suggest that bisphosphonates are an effective therapeutic tool in the treatment of GC-induced bone damage. Recent data on GC receptor-selective modulators indicate that these new molecules might induce only minimal bone loss while maintaining the typical anti-inflammatory properties of GC. Another new line of study for the prevention of GC-induced osteoporosis is the characterization of the individual's susceptibility to GC-induced bone damage.     

Glucocorticoid-induced osteoporosis.

Therapeutic use of glucocorticoids can lead to many well-known adverse events. Of all potential serious side effects, glucocorticoid-induced osteoporosis (GIOP) is one of the most devastating complications of protracted glucocorticoid therapy in rheumatoid arthritis. GIOP is the most common form of drug-induced osteoporosis. Although much has been written about the association of glucocorticoids with bone disease among patients with chronic inflammatory conditions, many issues remain unsettled. This article focuses on areas of continued controversies, including the epidemiology and pathogenesis of GIOP, specification of a "safe" dose, methods for diagnosis of GIOP, and an evidence-based approach for GIOP prevention.     

Post-transplantation hypoglycaemia in type 1 diabetic pancreas allograft recipients

Physiologic replacement of insulin in patients with type 1 (insulin-dependent) diabetes following pancreas allograft transplantation results in normoglycaemia during fasting and postprandial states. However, this is achieved at the expense of peripheral hyperinsulinaemia in the heterotopic pancreas allograft recipients with systemic insulin drainage. In addition, the pancreas allograft is denervated and thus devoid of autonomic nervous regulation of pancreatic beta-cell secretion. Recent reports of hypoglycaemia (symptomatic and asymptomatic), which can be fatal, have raised serious concerns regarding the aetiology of the hypoglycaemic epiphenomon in type 1 diabetic pancreas allograft recipients. Although the prevalence of significant hypoglycaemia following pancreas transplantation remains unknown, it is important to conduct studies to determine the mechanisms, the natural history, predictors and treatment as well as the long-term prognosis (graft and patient survival rates) of type 1 diabetic patients who develop pancreas-allograft-associated hypoglycaemia. Indeed, predictors of hypoglycaemia following pancreas allograft could significantly impact on the selection of appropriate therapeutic options for pancreas allograft transplantation. Finally, whether postpancreas allograft transplantation-associated hypoglycaemia in type 1 diabetic patients carries greater morbidity and mortality when compared to those without hypoglycaemia deserves to be investigated Received: 8 September 1998 / Accepted in revised form: 14 September 1998     

Treatment of osteoporosis.

No new compounds were tested in 1991, but more results on available therapeutic options were accumulated. Bisphosphonates and calcitonins appeared to increase bone density when used for a period of 1 to 3 years and to decrease vertebral fracture rate. Estrogen replacement therapy is still the most effective prevention of postmenopausal bone loss. Various studies revealed that the risk of inducing breast cancer has not been established and that estrogen has a strong protective effect against cardiovascular mortality. Screening for osteoporosis at menopause to target estrogen replacement therapy to women at increased fracture risk is recommended. Calcium and vitamin D supplements proved to be of significant value, especially in elderly people, in whom they even decreased fracture incidence. Fluoride demonstrated variable bioavailability. This might explain why certain fluoride studies showed fast increases in bone density with heavy side effects but no effect on fracture rate, whereas fluoride preparations of lower bioavailability were better tolerated and decreased fracture incidence. For almost all drugs, some dose dependence was demonstrated and maximally tolerated doses were established, but minimal effective doses are still unknown. Vertebral fracture rate was more often included as the final criterion in therapeutic trials, whereas long-term effects on hip fracture incidence still need more attention.     

Epidemiology of osteoporosis.

Osteoporosis is a major public health problem through its association with age-related fractures. Although fracture risk at any skeletal site depends upon a complex interaction between bone strength and trauma, recent epidemiologic studies confirm that bone density is currently the best single predictor of future fracture. The increasing burden of osteoporotic fractures urgently requires effective preventive strategies aimed at maximizing peak bone density, preventing excessive bone loss, and reducing the risk of falls.     

Pathogenesis of osteoporosis.

Osteoporosis is a very common disorder affecting millions of post-menopausal women and men of various ages. Although the disease is manifested by painful fractures of the spine, hip or radius, the underlying pathogenesis is complex and multifactorial. One of the strongest predictors of future osteoporotic fractures is low bone mineral density. The determinants of adult bone density include the rate of bone acquisition during adolescence and the absolute loss of bone during the six decades of adult life. Recent studies have clarified how bone mass is acquired during the early teen years in both boys and girls. Genetic factors play an enormous role in defining the height of acquisition of bone mass; however, these factors also interact with environmental and hormonal determinants. Many more studies have focused on adult bone loss. Disorders in bone remodelling result in an imbalance in bone turnover, favouring resorption over formation. Systemic factors such as oestrogen deprivation and parathyroid hormone strongly activate remodelling and can, in several circumstances, lead to imbalances in the remodelling cycle. The molecular cues that couple bone formation to resorption have recently been elucidated, and those factors may themselves become therapeutic targets for future treatment regimens to prevent osteoporosis and its resultant fractures.