scholarly journals Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011

2013 ◽  
Vol 70 (9) ◽  
pp. 848-853 ◽  
Author(s):  
Ljiljana Ignjatovic ◽  
Rajko Hrvacevic ◽  
Dragan Jovanovic ◽  
Zoran Kovacevic ◽  
Neven Vavic ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Immunosuppressive Therapy ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Solid Organ ◽  
Kidney Graft ◽  
Group I ◽  
Grade Iii

Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNIbased immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 ? 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and followe-up for 76 ? 13 months. Nine patients (the group I) had early postransplant conversion after 4 ? 3 months and 15 patients (the group II) late conversion after 46 ? 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 ? 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ? 12.7 to 69 ? 15 mL/min), while the increase in proteinuria (from 265 ? 239 to 530.6 ? 416.7 mg/day) and lipidemia (cholesterol from 4.71 ? 0.98 to 5.61 ? 1.6 mmol/L and triglycerides from 2.04 ? 1.18 to 2.1 ? 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 ? 232 to 1639 ? 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/min) and significantly improved proteinuria (from 1639 ? 1641 to 529 ? 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 ? 88 to 202 ? 91 mmol/L), decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/day) and increased proteinuria (from 528.9 ? 688 to 850 ? 1083 mg/min). Conclusion. In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications.

scholarly journals Torque teno viral load reflects immunosuppression in paediatric kidney-transplanted patients—a pilot study

2020 ◽  
Vol 36 (1) ◽  
pp. 153-162 ◽  
Author(s):  
Phoebe Uhl ◽  
Andreas Heilos ◽  
Gregor Bond ◽  
Elias Meyer ◽  
Michael Böhm ◽  
...  
Keyword(s):  
Viral Load ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Kidney Graft ◽  
Post Transplant ◽  
The Individual ◽  
Almost All ◽  
Plasma Load

Abstract Background Chronic deterioration of kidney graft function is related to inadequate immunosuppression (IS). A novel tool to assess the individual net state of IS in transplanted patients might be the monitoring of Torque teno virus (TTV) viral load. TTV is a non-pathogen virus detectable in almost all individuals. TTV level in the peripheral blood has been linked to the immune-competence of its host and should thus reflect IS after solid organ transplantation. Methods TTV plasma load was quantified monthly by RT-PCR for a period of 1 year in 45 kidney-transplanted children. Post-transplant time was at least 3 months. The relation of the virus DNA levels to IS and transplant-specific clinical and laboratory parameters was analysed longitudinally. Results TTV DNA was detectable in 94.5% of the plasma samples. There was a significant association with the post-transplant follow-up time as well as with the type of IS regimen, with lower virus loads in patients after longer post-transplant time and mTOR inhibitor–based IS. Furthermore, a significant positive correlation with the dose of prednisolone and mycophenolate mofetil was found. Conclusions TTV levels show an association/correlation with the strength of IS. Further studies are needed in order to evaluate TTV measurement as a tool for IS monitoring for hard clinical outcomes such as presence of donor-specific antibodies, rejections or infections—common consequences of insufficient or too intense IS.

scholarly journals MO195ATYPICAL HEMOLYTIC UREMIC SYNDROME IN LUNG TRANSPLANTATION: TREATMENT WITH ECULIZUMAB, OUR EXPERIENCE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Raquel Berzal Rico ◽  
Teresa Cavero Escribano ◽  
Pilar Aunon ◽  
Aida Frías González ◽  
Lucia Aubert ◽  
...  
Keyword(s):  
Platelet Count ◽  
Serum Creatinine ◽  
Lung Transplantation ◽  
Immunosuppressive Therapy ◽  
Solid Organ ◽  
Complement Factor ◽  
Renal Response ◽  
Uremic Syndrome ◽  
Lung Transplants

Abstract Background and Aims Atypical haemolytic uremic syndrome (aHUS) is a clinical entity characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. There are several cases of AHUS in non-renal solid organ transplants described in the literature, included lung transplant. Kidney and patient survival are compromised by this complication because of the lack of an effective treatment. Eculizumab is C5 complement factor specific blocker already administered in another kind of secondary aHUS with encouraging results Method We analys six lung transplants in a retrospective single-center study between 2018-2020 who developed an aHUS and were treated with eculizumab. Clinical and analytical data were collected along the follow-up. Principal outcome was to explore haematologycal and renal response after treatment with eculizumab. Results We included a total of six patients (83% were female) with a median age of 57 years at the time of transplantation. Aetiologies of lung transplantation were chronic obstructive pulmonary disease in 2 patients, interstitial lung disease in another 2, and cystic fibrosis in the remaining two. Induction and maintenance immunosuppressive therapy were based on tacrolimus, mycophenolate and prednisone in all cases. Baseline serum creatinine after lung transplantation was 1.1 mg/dl (0.9-2.4). Two patients developed an aHUS in the immediate post-transplant, one of them died because of surgical complications. Another four patients developed an aHUS 59 months (33-95) after transplantation. Previously of thrombotic microangiopathy, three patients were on treatment with everolimus instead of mycophenolate and two lung transplants have cytomegalovirus reactivation. At the aHUS onset, median serum creatinine was 4mg/dl (2.4-5-7) and acute dialysis was performed in 50% of patients. Median hemoglobin was 7.2g/dl (6.9-7.7), platelet count was 32x1000/µL (17-58), and DHL was 1343 U/L (581-1597) at the start of eculizumab despite having treated the trigger. After a median of 6 doses of eculizumab, the five surviving patients had haematologycal and renal response. No patients underwent chronic dialysis. Serum creatinine was 2.2 mg/dl (1.7-2.3), hemoglobin 9.8 g/dl and platelet count 159x1000/µL at the end of follow-up. Conclusion AHUS is a critical complication in lung transplantation, shortly related with immunosuppressive therapy. Patients are at risk of end stage renal disease. Eculizumab treatment appears promising.

scholarly journals Diffusion MRI Findings in Encephalopathy Induced by Immunosuppressive Therapy after Liver Transplantation

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Emanuele Tinelli ◽  
Nicoletta Locuratolo ◽  
Alberto Pierallini ◽  
Massimo Rossi ◽  
Francesco Fattapposta
Keyword(s):  
Liver Transplantation ◽  
Immunosuppressive Therapy ◽  
Cyclosporine A ◽  
Early Recognition ◽  
Brain Mri ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Neurological Complications ◽  
Solid Organ ◽  
Diffusion Weighted Images

Neurological complications are common after liver transplantation, as they affect up to one-third of the transplanted patients and are associated with significant morbidity. The introduction of calcineurin inhibitors, cyclosporine A and tacrolimus, in immunosuppressive regimens significantly improved the outcome of solid-organ transplantation even though immunosuppression-associated neurotoxicity remains a significant complication, particularly occurring in about 25% of cases after liver transplantation. The immunosuppressant cyclosporine A and tacrolimus have been associated with the occurrence of major neurological complications, diffuse encephalopathy being the most common. The biochemical and pathogenetic basis of calcineurin inhibitors-induced neurotoxicity are still unclear although several mechanisms have been suggested. Early recognition of symptoms could help reduce neurotoxic event. The aim of the study was to evaluate cerebral changes through MRI, in particular with diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps, in two patients undergoing liver transplantation after immunosuppressive therapy. We describe two patients in which clinical pictures, presenting as a severe neurological condition, early after orthotopic liver transplantation during immunosuppression therapy, showed a different evolution in keeping with evidence of focal-multifocal lesions at DWI and ADC maps. At clinical onset, DWI showed hyperintensity of the temporo-parieto-occipital cortex with normal ADC values in the patient with following good clinical recovery and decreased values in the other one; in the latter case, MRI abnormalities were still present after ten days, until the patient’s exitus. The changes in DWI with normal ADC may be linked to brain edema with a predominant vasogenic component and therefore reversible, while the reduction in ADC is due to cytotoxic edema and linked to more severe, nonreversible, clinical picture. Brain MRI and particularly DWI and ADC maps provide not only a good and early representation of neurological complications during immunosuppressant therapy but can also provide a useful prognostic tool on clinical outcome of the patient.

scholarly journals Interdisciplinary problem of post-transplant diabetes mellitus: literature review

2021 ◽  
Vol 12 (1) ◽  
pp. 60-73
Author(s):  
A. V. Balashova ◽  
V. R. Mustafina ◽  
I. V. Glinkina
Keyword(s):  
Diabetes Mellitus ◽  
Immunosuppressive Therapy ◽  
Survival Rates ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
World Health ◽  
Oral Glucose ◽  
Solid Organ ◽  
Post Transplant ◽  
Treatment And Prevention

The number of transplantation and transplant survival rates increase steadily. Patients after solid organ transplantation re-ceive lifelong immunosuppressive therapy which may have adverse effects on carbohydrate and lipid metabolism. The most diabetogenic drugs are calcineurin inhibitors and corticosteroids. Posttransplant diabetes mellitus (PTDM) is hyperglycemia that meets American Diabetes Association and World Health Organization diabetes criteria for nontransplant patients and that was newly diagnosed after transplantation. PTDM may worsen both short-term and long-term transplantation outcomes so that the problem of timely diagnosis, proper treatment and prevention is critical. In early post-transplant period, transient hyperglycemia is found in the vast majority of patients; therefore, PTDM screening is carried out at least one month after transplantation. The gold standard test for PTDM diagnosis is oral glucose tolerance test. In the same time diagnostic value of hemoglobin A1C is limited. Lifestyle therapy and antidiabetic drugs are considered as possible preventive measures. Stress induced hyperglycemia management in solid organ recipients is the same with other surgical patients. Which organ was transplanted, patient characteristics and possible drug interactions with immunosuppressive therapy should be taken into account while managing PTDM. Blood pressure and lipid profile should be under control for comprehensive cardiovascu-lar risk reduction. It remains unclear which PTDM treatment and prevention strategy is the best and for better understanding interdisciplinary approach is needed.

scholarly journals A Comparison of Allograft Survival Between Cyclosporine and Tacrolimus Based Immunosuppressive Therapy in Kidney Transplantation: BIRDEM General Hospital Experience

2016 ◽  
Vol 5 (2) ◽  
pp. 78-81
Author(s):  
Palash Mitra ◽  
Md Anisur Rahman ◽  
Muhammad Abdur Rahim ◽  
Mehruba Alam Ananna ◽  
Tasrina Shamnaz Samdani ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Serum Creatinine ◽  
Immunosuppressive Therapy ◽  
Graft Survival ◽  
Graft Function ◽  
Calcineurin Inhibitors ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Group 2 ◽  
Group 1

Introduction and Aims: Calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are one of the three major components of basic immunosuppressive therapy of kidney transplantation. Our aims were to study and compare the early and long-term graft survival in kidney transplant recipients who were receiving either of these two CNIs.Methods: A questionnaire was formed and data were collected from the hospital records. We divided the patients in group 1 (patients on cyclosporine) and group 2 (patients on tacrolimus). We retrospectively evaluated patients’ clinical and laboratory findings.Results: Group 1 included 50 patients who were on cyclosporine and group 2 included 61 patients who were on tacrolimus. Patients receiving tacrolimus showed almost similar renal function as cyclosporine receiving patients; serum creatinine was 1.27 ± 0.56 versus 1.42 ± 0.91mg/dL (p = 0.258), but they required less time for serum creatinine to become normal (4.71 ± 2.3 versus 7.26 ± 5.6 days, p=0.001) and less duration of post-transplant hospital stay (11.38 ± 3.33 versus 13.65 ± 5.0 days, p = 0.005). New onset diabetes was more pronounced in group 2 (29.5% versus 12 %, p = 0.025). On the other hand, acute rejection was only noted in group 1 (2 versus 0, p = 0.014). One-year and three-year graft survival for cyclosporine was 92.0% and 83.3%, and for tacrolimus was 96.2% and 89.2% respectively.Conclusions: Tacrolimus is relatively favourable to cyclosporine in preventing acute allograft rejection and better immediate post-transplant graft function recovery.Birdem Med J 2015; 5(2): 78-81

scholarly journals A case of rhabdomyolysis after atorvastatin therapy of a liver transplant recipient receiving immunosuppressive therapy with cyclosporine

2021 ◽  
Vol 13 (2) ◽  
pp. 158-164
Author(s):  
A. V. Shabunin ◽  
S. P. Loginov ◽  
P. A. Drozdov ◽  
I. V. Nesterenko ◽  
D. A. Makeev ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Drug Interactions ◽  
Liver Transplant ◽  
Immunosuppressive Therapy ◽  
Organ Transplantation ◽  
Muscle Pain ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Term Survival

Rationale. To date, liver transplantation is the most effective method of treating end-stage liver failure, and therefore this treatment has become widespread throughout the world. However, due to the improvement in the quality of transplant care and an increase in the long-term survival of patients, the development of concomitant pathology, which often requires medical treatment, is inevitably associated with a higher life expectancy of liver transplant recipients. Thus, in patients who underwent liver transplantation, there is. a significant increase in the incidence of dyslipidemia. However, a long-term immunosuppressive therapy in organ transplant patients can adversely modify the effect of the prescribed drugs, which requires careful monitoring and consideration of drug interactions.Purpose. Using a clinical example to demonstrate the importance of taking drug interactions into account in the treatment of patients after organ transplantation receiving immunosuppressive drugs.Material and methods. In the presented clinical case, a patient after orthotopic liver transplantation performed in 2005 underwent a staged treatment of cicatricial stricture of choledochal anastomosis in the S.P. Botkin City Clinical Hospital. During the following hospitalization, the patient complained of minor muscle pain when walking. At doctor's visit 3 weeks before hospitalization, a local physician prescribed therapy with atorvastatin 10 mg per day due to an increase in blood plasma cholesterol levels. The patient underwent removal of the self-expanding nitinol stent. During the follow-up examination, the patient had no evidence of an impaired bile outflow, however, muscle pain and weakness progressively increased, the rate of diuresis decreased, and in the biochemical analysis of blood there was an abrupt increase in the concentration of creatinine, aspartate aminotransferase, alanine aminotransferase. Atorvastatin was canceled, a diagnosis of acute non-traumatic rhabdomyolysis was established, treatment with hemodialysis and plasma exchange was started on 03/05/2020. The last session of renal replacement therapy was 03/30/20.Results. With the restoration of the diuresis rate, there was a spontaneous decrease in the level of creatinine to 170 μmol/L. The patient was discharged with satisfactory renal and hepatic function. The pain syndrome completely resolved. Conclusion. Drug interactions between atorvastatin and cyclosporine have resulted in acute rhabdomyolysis with life-threatening consequences. This once again confirms the importance of taking drug interactions into account when managing patients after solid organ transplantation.

scholarly journals Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation

2021 ◽  
Vol 11 ◽  
Author(s):  
Manuel Alfredo Podestà ◽  
Giuseppe Remuzzi ◽  
Federica Casiraghi
Keyword(s):  
Organ Transplantation ◽  
Patient Survival ◽  
Immunosuppressive Agents ◽  
Graft Function ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Clinical Models ◽  
Transplant Failure

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.

Case 14

2020 ◽  
pp. 87-92
Author(s):  
Hilary Humphreys
Keyword(s):  
Point Of Care ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Poor Countries ◽  
Treatment Regimens ◽  
Bird Droppings ◽  
Opportunist Infection ◽  
Immunosuppressed Patients ◽  
Respiratory Specimens

Cryptococcosis is an opportunist infection that should be considered in HIV/AIDS and in other at risk immunosuppressed patients such as those following solid organ transplantation. Cryptococcus neoformans is found in bird droppings and is the commonest cause in temperate climates but C. gattii is increasingly recognized in warmer climates. Diagnosis is usually via antigen detection, microscopy, and culture of blood, respiratory specimens and cerebrospinal fluid (CSF), in addition to histological analysis of appropriate tissue with specialised stains. New antigen assays facilitate point-of-care testing in resource-poor countries. Management includes initial treatment regimens with liposomal amphotericin B (the echinocandins have little activity) followed by follow-up antifungal therapy for up to a year, usually with fluconazole.

Metabolic Consequences of Solid Organ Transplantation

2020 ◽  
Author(s):  
Mamatha Bhat ◽  
Shirine E Usmani ◽  
Amirhossein Azhie ◽  
Minna Woo
Keyword(s):  
Metabolic Disease ◽  
Weight Gain ◽  
Dietary Habits ◽  
Solid Organ Transplantation ◽  
Calcineurin Inhibitors ◽  
Metabolic Effects ◽  
Current Evidence ◽  
Solid Organ ◽  
Metabolic Complications ◽  
Nonalcoholic Fatty Liver

Abstract Metabolic complications affect over 50% of solid organ transplant recipients. These include posttransplant diabetes, nonalcoholic fatty liver disease, dyslipidemia, and obesity. Preexisting metabolic disease is further exacerbated with immunosuppression and posttransplant weight gain. Patients transition from a state of cachexia induced by end-organ disease to a pro-anabolic state after transplant due to weight gain, sedentary lifestyle, and suboptimal dietary habits in the setting of immunosuppression. Specific immunosuppressants have different metabolic effects, although all the foundation/maintenance immunosuppressants (calcineurin inhibitors, mTOR inhibitors) increase the risk of metabolic disease. In this comprehensive review, we summarize the emerging knowledge of the molecular pathogenesis of these different metabolic complications, and the potential genetic contribution (recipient +/− donor) to these conditions. These metabolic complications impact both graft and patient survival, particularly increasing the risk of cardiovascular and cancer-associated mortality. The current evidence for prevention and therapeutic management of posttransplant metabolic conditions is provided while highlighting gaps for future avenues in translational research.

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