Adverse Effects Of Immunosuppression Research Articles

Surgery of the airway: historic notes.

Prior to the 20(th) century, the need for surgical procedures on the airway was infrequent and consisted mainly of tracheostomy to relieve airway obstruction or repair of tracheal injuries such as lacerations. Even the ability of tracheal suture lines to heal primarily was viewed with concern due to the rigidity of the tracheal wall, its precarious blood supply and uncertainty as to whether the cartilage components could heal without complications. In the 20(th) century the evolution of tracheal procedures on major airways evolved to meet the challenges provided by the expanding fields of thoracic surgery and advent of mechanical respiratory support with its associated complications. In the first half of the century lobar and lung resections done for tuberculosis and lung cancer required methods for safe closure of the resulting bronchial stumps and end-to-end bronchial anastomosis in the case of sleeve resections of the lung. Beginning in mid-century the advent of respiratory care units for the treatment of polio and for the expanding fields of thoracic and cardiac surgery resulted in a significant number of post-intubation tracheal stenosis requiring resection and primary repair. In the last 20 years of the century the development of lung transplantation with its requirement for successful bronchial anastomoses between the donor and recipient bronchi, created unique challenges including ischemia of the donor bronchus the adverse effects of immunosuppression, donor lung preservation and diagnosis and management of post-transplant infection and rejection.

Nutrition therapy: Integral part of liver transplant care.

Managing malnutrition before liver transplantation (LTx) while on the waiting list and, excessive weight gain/metabolic disturbances in post-surgery are still a challenge in LTx care. The aim of this review is to support an interdisciplinary nutrition approach of these patients. Cirrhotic patients are frequently malnourished before LTx and this is associated with a poor prognosis. Although the relation between nutritional status versus survival, successful operation and recovery after LTx is well established, prevalence of malnutrition before the operation is still very high. Emerging research has also demonstrated that sarcopenia pre and post-transplant is highly prevalent, despite the weight gain in the postoperative period. The diagnosis of the nutritional status is the first step to address the adequate nutritional therapy. Nutritional recommendations and therapy to manage the nutritional status of LTx patients are discussed in this review, regarding counseling on adequate diets and findings of the latest research on using certain immunonutrients in these patients (branched chain amino-acids, pre and probiotics). Nutrition associated complications observed after transplantation is also described. They are commonly related to the adverse effects of immunosuppressive drugs, leading to hyperkalemia, hyperglycemia and weight gain. Excessive weight gain and post-transplant metabolic disorders have long been described in post-LTx and should be addressed in order to reduce associated morbidity and mortality.

Post-transplant Metabolic Syndrome (PTMS) after Liver Transplantation –Review of the Literature

Liver transplant provides a definitive therapeutic measure for patients with chronic and acute liver diseases. Apart from the improvement of overall health, an organ transplant entails several metabolic complications. They are multi-agent and depend, among others, on the function of organ being transplanted, adverse effects of immunosuppression being applied, organ complications induced by failure of the organ being transplanted, current treatment, concomitant diseases and consequences of the acute and chronic rejection processes. Improvements in surgical techniques, peritransplant intensive care, and immunosuppressive regimens have resulted in significant improvements in short-term survival. Focus has now shifted to address long-term outcomes of liver transplantation. Therefore, this paper presents the current review of literature referring to specificity of the prevalence of metabolic syndrome and its complications in patients after liver transplantation.

Authors’ Response to: Platelet Indices in Renovascular Thrombosis After a Renal Transplant

We would like to thank Dr. Varol for his recent interest in our article that evaluated mean platelet volume (MPV) before and after renal transplant as a potential predictor of renovascular thrombosis.1 He asked for the methodology of blood sampling to measure MPV in our study. Previously, it was suggested to use tubes with a high concentration of sodium citrate to obtain more reliable measures of MPV.2 However, this recommendation did not meet routine practice demands. Instead, most laboratories, as in our institution, continue to rely on ethylene diaminetetraacetic acid as the standard hematologic anticoagulant by further shortening processing times.3 Mean platelet values have been shown to be independent of the anticoagulation with ethylenediaminetetraacetic acid or citrate if measured within 1 hour of sampling.4 In accord with this recommendation, full blood counts of all the patients at our institution are routinely measured in K3 ethylenediaminetetraacetic acid within 15 minutes of venipuncture. Many factors are known to influence the MPV including smoking, obesity, diabetes mellitus, prediabetes, hypertension, hypercholesterolemia, the metabolic syndrome, some antihypertensive agents, and immunosuppressive drugs. In our study, all patients were children, and none of them smoked. As specified in our original article, obesity was not seen in any of our patients before transplant, and the MPV levels were measured, and found to be decreased by the end of the first month after transplant. In such a short time, no serious weight loss was seen in any patients. None of the patients had a diagnosis of diabetes mellitus or prediabetic status. Hypertension is a prevalent complication occurring in 80% to 85% of all kidney transplant recipients. The pathogenesis of posttransplant hypertension is multifactorial including pretransplant hypertension, donor hypertension, renin secretion from the native kidney, graft dysfunction, recurrent disease, and immunosuppressive treatment.5 Conversely, an abnormally high prevalence of the metabolic syndrome has been seen in patients receiving solid-organ transplants, and some of the pathogenetic factors might include cyclosporine and corticosteroids.6 In our study, no significant differences in blood pressures and serum lipid profiles were seen in any of the patients, either before or after renal transplant. We know that hyperglycemia, hypercholesterolemia, hypertension, and thrombocytopenia are associated with high MPV levels, and such adverse effects of immunosuppressive drugs (cyclosporine or tacrolimus in combination with mycophenolate mofetil and prednisolone) were noted.5-7 There is a paucity of research that investigates the relation between the MPV and use of immunosuppressive agents. In general, increases in the MPV have been reported. Reis and associates compared the effects of sirolimus and cyclosporine, and found that hemoglobin, hematocrit, MPV, and platelet distribution width were significantly higher in the sirolimus group than in the cyclosporine group.8 In another study, Gasparyan and associates9 reported a significant increase in MPV after anti–TNF-alpha therapy in patients with rheumatoid arthritis, but

Inverse Association of Serum Osteocalcin and Bone Mineral Density in Renal Transplant Recipients

Objective: Osteoporosis is prevalent in transplant recipients and is related to pre- and post-transplantation factors. Low bone mass and fractures may antedate transplantation, related to traditional risk factors for osteoporosis, effects of chronic illness, and end-stage renal disease and its therapy on the skeleton. Bone loss after kidney transplantation (KT) is related to adverse effects of immunosuppressive drugs on bone remodeling. This study was undertaken to evaluate the relationship between bone mass density (BMD) and fasting serum osteocalcin in KT patients. Methods: Fasting blood samples were obtained from 69 KT patients. BMD was measured by dual energy X-ray absorptiometry in lumbar spine. Lumbar spine T-score < -2.5 is defined as osteoporosis, and T-score between -1.0 and -2.5 is defined as osteopenia as according to World Health Organization (WHO) criteria. Serum osteocalcin levels were measured using a commercial enzyme immunoassay kit. Results: Eight patients (11.6%) had osteoporosis and twenty-eight patients (40.6%) had osteopenia in renal transplant recipients. Increased serum osteocalcin (p < 0.001) was significantly correlated with low lumbar T-score cut-off points between groups (normal, osteopenia, and osteoporosis) in renal transplant recipients. Female patients had lower lumbar BMD than male renal transplant recipients (p = 0.013). Univariate linear regression analysis indicated lumbar BMD were positively correlated with height (p = 0.016), body weight (p = 0.001), and body mass index (BMI; p = 0.015), while negatively correlated with age (p = 0.039), osteocalcin (p = 0.001) among the renal transplant recipients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that osteocalcin (R2 change = 0.163; p = 0.028), age (R2 change = 0.056; p = 0.009) and body weight (R2 change = 0.075; p = 0.011) were the independent predictors of lumbar BMD values in the renal transplant recipients. Conclusions: Serum osteocalcin concentration correlates negatively with lumbar BMD values in renal transplant recipients.

Awareness of Memory Impairment Increases the Adherence to Immunosuppressants in Kidney Transplant Recipients

ObjectivesNonadherence to immunosuppressive drugs is a concern among kidney transplantation recipients (KTRs). The adverse effects of immunosuppressive drugs can trigger nonadherence and lead to a great impact on the allograft survival. The aim of this prospective controlled study is to determine the major adverse effects of immunosuppressive drugs and their correlation with the nonadherence in kidney transplantation recipients. MethodsAll data were collected from medical and pharmacy records. We use modified Immunosuppressant Therapy Adherence Scale combined with Modified Transplant Symptom Occurrence and Symptom Distress scale to explore the relationship between symptom experience related to side effects of immunosuppressants and adherence. The risk of nonadherence was estimated by stepwise logistic regression while controlling for age, gender, education, and immunosuppressive medications. Multivariable analysis was performed using a single random effect of P < .2. ResultsIn total, 412 KTRs completed the structured self-report instrument. The weekly pill counts were 84.2 ± 39.8. Overall, 21.4% of patients were nonadherent to immunosuppressive drugs. The most common adverse effects of immunosuppressive drugs were memory impairment (28.4%), insomnia (26.0%), gastrointestinal discomfort (21.4%), easy fatigue (22.1%), hand tremor (23.8%), and vision variation (29.1%). Multivariate analysis revealed that the adherence increased in patients with awareness of memory impairment (odds ratio 2.320, 95% confidence interval: 1.259–4.274, P = .007). There was no significant difference in the incidence of acute rejection, gender, age, and education between adherent and nonadherent patients. ConclusionIn summary, these results indicate a significant prevalence of nonadherence to immunosuppressive drugs in kidney transplantation recipients. Awareness of memory impairment significantly affected adherence to immunosuppressive drugs.

How regenerative medicine and tissue engineering may complement the available armamentarium in gastroenterology?

The increasing shortage of donors and the adverse effects of immunosuppression have restricted the impact of solid organ transplantation. Despite the initial promising developments in xenotransplantation, roadblocks still need to be overcome and this form of organ support remains a long way from clinical practice. While hepatocyte transplantation may be effectively correct metabolic defects, it is far less effective in restoring liver function than liver transplantation. Tissue engineering, using extracellular matrix scaffolds with an intact but decellularized vascular network that is repopulated with autologous or allogeneic stem cells and/or adult cells, holds great promise for the treatment of failure of organs within gastrointestinal tract, such as end-stage liver disease, pancreatic insufficiency, bowel failure and type 1 diabetes. Particularly in the liver field, where there is a significant mortality of patients awaiting transplant, human bioengineering may offer a source of readily available organs for transplantation. The use of autologous cells will mitigate the need for long term immunosuppression thus removing a major hurdle in transplantation.

Cardiovascular Risk in Kidney Transplant Recipients Receiving Mammalian Target of Rapamycin Inhibitors

Cardiovascular diseases (CVD) are the leading cause of mortality in renal transplant recipients. Various traditional and unconventional cardiovascular risk factors are potentiated by the adverse effects of immunosuppressive drugs. The mammalian target of rapamycin (mTOR) inhibitors have shown cardioprotective effects in experimental studies, but their influence on CVD in renal transplantation is unclear. The study included 115 kidney transplant recipients treated with mTOR inhibitors with steroids. A group of 38 patients received additionally small doses of calcineurin inhibitor. The control group consisted of 58 kidney transplant recipients randomly chosen among the population of patients transplanted at the same time, who received a calcineurin inhibitor, mycophenolate mofetil or sodium plus steroids. No differences in age, gender, duration of pretransplantat dialysis, time after transplantation, body mass index or glycated hemoglobin existed between the groups. Blood pressure and number of antihypertensive agents, high-density lipoprotein cholesterol, and uric acid levels were similar. The prevalence of diabetic, ischemic, or hypertensive nephropathy as the reason for end-stage renal disease was similar ( P = .08). The study group showed higher mean values of total cholesterol (249 vs 204.6 mg/dL; P < .0001) and low-density lipoprotein 136.5 vs 117.7 mg/dL; ( P = .015), as well as median values of triglycerides (202 vs 142 mg/dL; P < .0001) and proteinuria ( P = .0002). mean estimated glomerular filtration rate was lower in the study group (42.9 vs 51.9 mL/min; P = .0003). Posttransplant diabetes appeared in 38% of the study group compared to 20% of the controls ( P = .08). The incidence of coronary artery disease was higher among patients treated with mTOR inhibitors ( P = .04). CVD, defined as myocardial infarction, percutaneous coronary intervention, stroke, aortic aneurysm, pulmonary thromboembolism, sudden cardiac death appeared in 26 study group compared with four control patients ( P = .24). The risk of any CVD was not significantly higher among patients receiving mTOR inhibitors hazard ratio 1.94; 95% confidence interval 0.83–4.52). In conclusion, no correlation was observed between the duration of mTOR therapy and CVD.

Is Age a Limiting Factor for Access to Transplantation?

As a result of increased life expectancy and quality of life, there is an increasing number of patients older than 65 years of age who require the possibility of heart transplantation (HTx). Traditionally, recipient age older than 65 years has been considered a contraindication for performing a HTx because these patients have more comorbidities, are more affected by the adverse effects of immunosuppressive drugs, and obtain a smaller benefit in the medium and long term. Therefore, given the shortage of donors, priority was given to younger recipients. In recent years, studies have been published demonstrating that HTx in this population segment is possible. These results indicate that despite suffering more infections and having longer hospital stays, these patients have fewer rejections, with an overall survival in the medium and long term similar to that of HTx in younger patients. These results have been achieved partly as a result of appropriate selection of recipients and emergence of new immunosuppressive agents that has allowed their use to be individualized to the characteristics and comorbidities of each patient. Despite the latest advances, longer-term multicenter studies are required to clarify the role of alternate lists and the impact of new ventricular assist devices in this population segment.

The influence of pharmacogenetics and cofactors on clinical outcomes in kidney transplantation

Introduction: Immunosuppressive drugs have a narrow therapeutic range and large inter-individual response variability. This has prompted pharmacogenetic studies, mostly with regard to their dose–concentration relationships, but also about proteins involved in their pharmacodynamics. Some polymorphisms of genes involved in their disposition pathways were shown to affect their dose–concentration relationships. The impact of pharmacogenetics on tissue distribution and the resulting clinical effects have less often been studied. More importantly, a few single nucleotide polymorphisms seem to have a significant impact on the incidence of acute rejection or the adverse effects of immunosuppressants. Environmental factors often interact with such genotype–phenotype relationships.Areas covered: This article reviews the impact of genetic polymorphisms of the metabolic enzymes, membrane transporters and target proteins of mycophenolic acid, calcineurin inhibitors and mammalian target of rapamycin inhibitors on clinical outcomes in kidney transplantation.Expert opinion: The current level of evidence is not yet high enough to recommend pharmacogenetic personalization of immunosuppressive regimens in transplant recipients. The prevention of cellular toxicity associated with local metabolism or transport, which cannot be addressed by routine monitoring, is worth investigating further.

Histoire du progrès médical en transplantation rénale. À propos d’une série de 3 000 transplantations consécutives réalisées dans le CHU de Bicêtre

Major medical progress has been made in the field of renal transplantation over the last 40 years, thanks to advances in areas such as metabolism, immunology, therapeutics, and pathology. This progress has been accompanied by important changes in French legislation that governs organ harvest and transplantation, as well as the institutions that regulate organ allocation. Patient and graft survival have both increased markedly, although long-term improvements have been somewhat offset by complications, including adverse effects of immunosuppression. On average recipients are older than in the past and some recipients are now dying from age-related comorbidities despite having functional grafts.

Adverse Effects of Immunosuppression in Pediatric Solid Organ Transplantation

Solid organ transplantation is a life-saving treatment for end-stage organ failure in children. Immunosuppressant medications are used to prevent rejection of the organ transplant. However, these medications are associated with significant adverse effects that impact growth and development, quality of life (QOL), and sometimes long-term survival after transplantation. Adverse effects can differ between the immunosuppressants, but many result from the overall state of immunosuppression. Strategies to manage immunosuppressant adverse effects often involve minimizing exposure to the drugs while balancing the risk for rejection. Early recognition of immunosuppressant adverse effects may help to reduce morbidities associated with solid organ transplantation, improve QOL, and possibly increase overall patient survival.

Structure of GroEL in Complex with an Early Folding Intermediate of Alanine Glyoxylate Aminotransferase

Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have previously shown that P11L and I340M polymorphisms together with I244T mutation (AGXT-LTM) represent a conformational disease that could be amenable to pharmacological intervention. Thus, the study of the folding mechanism of AGXT is crucial to understand the molecular basis of the disease. Here, we provide biochemical and structural data showing that AGXT-LTM is able to form non-native folding intermediates. The three-dimensional structure of a complex between the bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been solved by cryoelectron microscopy. The electron density map shows the protein substrate in a non-native extended conformation that crosses the GroEL central cavity. Addition of ATP to the complex induces conformational changes on the chaperonin and the internalization of the protein substrate into the folding cavity. The structure provides a three-dimensional picture of an in vivo early ATP-dependent step of the folding reaction cycle of the chaperonin and supports a GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM mutant protein through forced unfolding mechanism.

A Colloquium on the Congress “A Gift for Life. Considerations on Organ Donation”

Alessandro Nanni Costa, J. M. Simon i Castellvi, Antonio G. Spagnolo, Nunziata Comoretto, Jean Laffitte, Hakan Gabel, Francis L. Delmonico, Ferdinand Muehlbacher, Walter Schaupp, Alexandra K. Glazier, Valter D. Garcia, Mario Abbud-Filho, Jose O. Medina-Pestana, Mariangela Gritta Grainer, Pier Paolo Donadio, Anna Guermani, Riccardo Bosco, Francesco Giordano, Blanca Martinez Lopez de Arroyabe, Marco Brunetti, Marti Manyalich, Gloria Paez, Ricardo Valero, Rafael Matesanz, Elisabeth Coll, Beatriz Dominguez-Gil, Beatriz Mahillo, Eduardo Martin Escobar, Gregorio Garrido, and Felix Cantarovich

Outcome After Steroid Withdrawal in Heart Transplantation

There is a lack of consensus and insufficient data to assess the impact of late steroid withdrawal after heart transplantation (HTx). The aim of the study was to investigate the security and feasibility of corticosteroid withdrawal at 1 year after transplantation. Steroid withdrawal was attempted after at least 12 months of treatment in 86 HTx patients who fulfilled the criteria. At 1 and 3 months after drug discontinuation, patients underwent 2 endomyocardial biopsies (EMB). After a mean follow-up of 25 +/- 13 months, 63% of the patients remained steroid free. In 30 patients (35%) corticosteroids were reinitiated, in 15 cases because of acute rejection (7%), 5 (6%) because of worsening renal function, 5 (6%) because of malignancy, 3 (4%) because of adverse effects of immunosuppressive drugs, and 2 because of severe allograft coronary artery disease. Four patients (5%) died after drug discontinuation. There was a significant decrease in total cholesterol (198 +/- 35 to 181 +/- 38 mg/dL; P < .001) and low-density lipoprotain (LDL) cholesterol levels (113 +/- 30 to 105 +/- 30 mg/dL; P < .001). There were no differences in mortality between patients with and without corticosteroids. Steroid withdrawal is feasible and safe in HTx patients. In our study, it was successfully maintained in 63% of the patients. EMB is helpful to identify patients with acute rejection at 1 and 3 months after withdrawal. Short- to mid-term metabolic benefits are significant reductions in serum total and LDL cholesterol.

A Survey of North American Hand Surgeons on Their Current Attitudes Toward Hand Transplantation

Although composite tissue allotransplantation (CTA) is unparalleled in its potential to reconstruct "like with like," the risk-benefit ratio and clinical indications are difficult to determine. We examined current attitudes regarding the emerging field of CTA from those who treat complex hand injuries. A web-based survey regarding CTA was sent to members of the American Society for Surgery of the Hand, which identified their demographic data and practice profiles. Respondents' support for CTA and their assessment of the level of risk associated with these procedures were addressed. Additional questions focused on the clinical application of CTA with current immunosuppression, ethical issues surrounding CTA, and the indications for hand transplantation. Finally, 2 clinical situations that closely mirrored past hand transplantations were presented, and members evaluated their suitability for allotransplantation. A total of 474 surgeons responded to the survey (22% response rate), who were divided in their opinion of hand transplantation with 24% in favor, 45% against, and 31% undecided. The majority (69%) consider this surgery to be a high-risk endeavor; however, a large percentage (71%) still believe it to be an ethical procedure when performed on properly selected patients. The most accepted indications for hand transplantation were loss of bilateral hands (78%) and amputation of a dominant hand (32%). Only 16% were in favor of performing transplants with the immunosuppression available today. In response to the clinical situation, 66% would offer transplantation to a bilateral hand amputee, whereas only 9% would offer transplantation to a patient with diabetes who had lost his or her dominant hand. This survey demonstrates support for hand allotransplantation as a solution for dominant-hand and bilateral hand amputees. However, surgeons continue to be concerned about the adverse effects of immunosuppression and the risks of acute and chronic rejection, and many want to wait for the development of better immunologic treatment options.

Systemic rheumatic diseases in the ICU

Patients with systemic rheumatic diseases may be admitted to the ICU because of pulmonary, renal or multiple organ dysfunction, caused by worsening of the rheumatic disease, infection or adverse effects of immunosuppressive drugs.

Pregnancy in Women with Renal Disease. Part I: General Principles

The purpose of this review is to improve the basis upon which advice on pregnancy is given to women with renal disease and to address issues of obstetric management by drawing upon the accumulated world experience. To ensure the proper rapport between the respect for patient's autonomy and the ethical principle of beneficence, the review attempts to impart up-to-date, evidence-based information on the predictable outcomes and hazards of pregnancy in women with chronic renal disease. The physiology of pregnancy from the perspective of the affected kidney will be discussed as well as the principal predictors of maternal and fetal outcomes and general recommendations of management. The available evidence supports the implication that the degree of renal function impairment is the major determinant for pregnancy outcome. In addition, the presence of hypertension further compounds the risks. On the contrary, the degree of proteinuria does not demonstrate a linear correlation with obstetric outcomes. Management and outcome of pregnancies occurring in women on dialysis and after renal transplant are also discussed. Although the outcome of pregnancies under chronic dialysis has markedly improved in the past decade, the chances of achieving a viable pregnancy are much higher after transplantation. But even in renal transplant recipients, the rate of maternal and fetal complications remains high, in addition to concerns regarding possible adverse effects of immunosuppressive drugs on the developing embryo and fetus.

Osteoporosis following solid organ transplantation

Damaris Vega & Khashayar Sakhaee† †Author for correspondence University of Texas Southwestern Medical Center, Department of Internal Medicine and, Charles & Jane Pak Center for Mineral Metabolism & Clinical Research, 5323 Harry Hines Boulevard, Dallas, TX 75390-8885, USA Tel.: +1 214 590 7783; Fax: +1 214 590 4091; khashayar.sakhaee@utsouth western.edu ‘Despite the introduction of new immunosuppressive regimens designed for renal allograft recipients ... post-transplantation bone disease remains a major complication in this population.’ Since the introduction of new immunomodulatory agents, the number of organ transplants has increased significantly worldwide. Approximately 28,000 subjects received solid organ transplants in the USA from 2005 to 2006 [101] – approximately double the number of solid organ transplants performed in 1988. Despite the introduction of new immunosuppressive regimens designed for renal allograft recipients, including cyclosporine and tacrolimus, post-transplantation bone disease remains a major complication in this population. It was once thought that the introduction of these new immunomodulatory agents and the limited use of glucocorticoids would ameliorate this complication. However, the sustained loss of bone mineral density and spontaneous bone fractures remain a major cause of morbidity in these subjects [1–5]. The pathophysiologic mechanisms responsible for osteoporosis following organ transplantation are diverse and multifactorial [6]. The most common responsible factors include the underlying conditions leading to transplantation, lifestyle and nutritional changes, hormonal dysregulations, including abnormalities in calcitropic and gonadal hormones, and the skeletal effects of immunomodulatory agents [7–9]. Most commonly, medical immunosuppression has been implicated as the leading catalyst in the development of post-transplantation bone disease [10–13]. However, various renal, hepatic, cardiac and pulmonary diseases also have specific pathophysiologies that may contribute to the outcome of bone disease in this population [14–33]. Careful consideration should be given to the unique clinical picture of each individual patient before and after transplantation. Such a characterization will facilitate optimal management of this diverse group of patients to decrease the incidence of bone fractures and ultimately improve their quality of life. Bone disease is commonly encountered in chronic renal failure patients who experience a continual decline in renal function. Secondary hyperparathyroidism may persist following successful renal transplantation and potentially accentuate the adverse effects of immunosuppressive drugs on the development of bone disease [34]. In addition, the synergistic effect of parathyroid hormone and elevated serum concentrations of phosphatonins, including FGF-23, which has been demonstrated to be elevated after renal transplantation, result in renal phosphorus wasting by reducing renal tubular reabsorption [35–38]. Persistent phosphorus depletion will potentially contribute to defective bone mineralization and progression to osteomalacia and low bone turnover. However, these complications have been largely unnoticed. Therefore, the magnitude of skeletal abnormalities following renal transplantation are much broader than in other solid organ transplantations [39]. These factors may be partly responsible for the continued loss of bone mineral density and increased cumulative risk of new fractures following renal transplantation [3]. Moreover, glucocorticoid treatment, by uncoupling of bone resorption and bone formation, may attenuate the recovery of an impaired bone turnover caused by adynamic bone disease − the most predominant skeletal lesion encountered in patients during dialysis treatment [11,31,40–42].

Folgeerkrankungen nach gastrointestinalen Operationen

Gastrointestinal surgery may not only lead to early postoperative complications but also chronic consequences. These have therapeutic implications for affected patients. The kind and extent of surgical intervention determines the spectrum of postsurgical phenomena which may occur. These chronic consequences are due to changes in gastrointestinal anatomy, the synchronization of digestive processes, or the ability to digest and absorb food. In case of transplantation surgery, adverse effects of immunosuppression have to be considered. Sometimes, chronic consequences of surgical procedures are difficult to recognize. The knowledge of typical problems associated with gastrointestinal surgery is necessary to enable early and timely diagnosis and treatment. Some negative effects can be avoided by early therapeutic interventions. This article summarizes typical chronic consequences of gastrointestinal surgery.