tacrolimus and Respiratory-Insufficiency

Although significant gains have been made in improving lung function and survival in cystic fibrosis (CF), ultimately respiratory failure is the leading cause of mortality in these patients. For CF patients with end stage lung disease, lung transplantation is an option for treatment. The field of lung transplantation has progressed markedly in the last 20 years. Nonetheless it remains a technically complex and challenging procedure, and patients are at risk for numerous short term and long term complications. Potential transplant recipients must be physically and psychologically prepared for the arduous process involved in lung transplantation. This article will review the history of lung transplantation, indications for transplantation, surgical techniques, and complications of transplantation.

Topics: Bronchiolitis Obliterans; Cystic Fibrosis; Graft Rejection; Heart-Lung Transplantation; Humans; Lung Transplantation; Respiratory Insufficiency; Tacrolimus; Tissue Donors

We aimed to identify clinical settings of renal transplant patients with COVID-19.. In this retrospective study, we included kidney transplant inpatients with laboratory confirmed COVID-19 who had been discharged or had died by October 1st, 2020. Characteristics of the patients, including basal and last outpatient biochemical parameters were recorded. Discontinuation or dosage reduction of immunosuppressives and other treatment information was documented.. Twenty patients were included in this study, of whom 18 were discharged and 2 died in hospital. The mean duration of hospitalization and follow-up were 9.7 ± 6.4 days and 4.5 ± 2.0 months, respectively. Fourteen patients (70%) were male and mean age was 48.0 ± 10.3 years. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/ day (50%) or dexamethasone (50%). Tacrolimus/m-TOR inhibitors were reduced by 50% and all antimetabolites were discontinued. Hemodialysis was needed for 10% of patients. Acute kidney injury was detected in 25% of the patients. With respect to hospitalization time and complications, there was no significant difference between patients who used dexamethasone and those who did not (P > 0.05). The discontinued immunosuppressives were resumed within 2 to 4 weeks after discharge according to the severity of disease. No rehospitalization or acute rejection was detected during the follow-up of the patients.. Renal transplant patients are considered a high risk group for COVID-19. It can be said that discontinuation or reducing dosages of immunosuppressives may be effective and safe in kidney transplant patients.

Topics: Acute Kidney Injury; Adult; COVID-19; Deprescriptions; Dexamethasone; Disease Progression; Everolimus; Female; Glucocorticoids; Graft Rejection; Hospital Mortality; Hospitalization; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Length of Stay; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Renal Dialysis; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; SARS-CoV-2; Sepsis; Tacrolimus

Topics: Anti-Bacterial Agents; Antibodies, Antinuclear; Autoantigens; Cyclophosphamide; Extracorporeal Membrane Oxygenation; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Middle Aged; Myositis; Oxygen Inhalation Therapy; Respiratory Insufficiency; Ribonucleoproteins; Rituximab; SS-B Antigen; Tacrolimus

Topics: Adolescent; Adult; Aged; Cyclosporine; DNA, Viral; Female; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Respiratory Insufficiency; Retrospective Studies; Tacrolimus; Torque teno virus; Viral Load; Virus Replication; Young Adult

Cyclosporine is usually administered orally in two divided doses every 12 h in transplant patients. However, some patients have difficulty in achieving therapeutic levels after transplantation. In fact, cyclosporine is reportedly administered once daily in renal and liver transplantation cases, but not in lung transplantation cases. We report a patient with a history of calcineurin inhibitor-induced renal toxicity who successfully underwent living-donor lobar lung transplantation (LDLLT) with the novel immunosuppressive strategy of once-daily administration of cyclosporine. An 18-year old man with progressive respiratory insufficiency after bone marrow transplantation was referred to our hospital for lung transplantation. He had a history of renal toxicity due to calcineurin inhibitors. Based on his history of tacrolimus- and cyclosporine-induced renal toxicity, we decided to initiate basiliximab as induction therapy, followed by once-daily cyclosporine administration to obtain high enough blood cyclosporine concentrations at 2 h post-dose (C2) and lowered trough blood concentrations (C0) for protection of renal function as maintenance therapy. LDLLT was successfully performed, and the postoperative course was uneventful and free of rejection episodes. Cyclosporine dosing was adjusted with intensive therapeutic drug monitoring of blood cyclosporine levels. One year after LDLLT, the patient is alive and well with no problems with daily life activities.

Topics: Administration, Oral; Adolescent; Calcineurin Inhibitors; Cyclosporine; Drug Administration Schedule; Drug Monitoring; Graft Rejection; Graft Survival; Humans; Kidney Diseases; Lung Transplantation; Male; Respiratory Insufficiency; Tacrolimus; Time Factors; Treatment Outcome

Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function.

Topics: Acute Disease; Adult; Antibodies, Monoclonal; Basiliximab; Coinfection; Cystic Fibrosis; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lung Transplantation; Male; Mycophenolic Acid; Pneumonia; Prednisone; Recombinant Fusion Proteins; Recovery of Function; Renal Dialysis; Respiratory Insufficiency; Tacrolimus

Topics: Acute Disease; Adult; Animals; Fatal Outcome; Female; Humans; Ivermectin; Kidney Transplantation; Larva; Mycophenolic Acid; Prednisone; Respiratory Insufficiency; Strongyloides stercoralis; Strongyloidiasis; Tacrolimus

Topics: Adult; Bilirubin; Cystic Fibrosis; Hepatitis C; Hepatocytes; Humans; Immunosuppressive Agents; Liver; Liver Diseases; Lung Transplantation; Male; Respiratory Insufficiency; Tacrolimus

A 64-year-old woman underwent allogeneic peripheral blood-derived stem cell transplantation for acute lymphocytic leukemia. She complained of dyspnea and was admitted to hospital 116 days after transplantation. Because of positive serum testing for the Aspergillus antigen and antibody, and ground-glass opacity in the right upper lobe on high-resolution computed tomography (HRCT), we made a diagnosis of pulmonary aspergillosis and administered an antifungal agent. Although tests for the Aspergillus antibody became negative and the ground-glass opacities disappeared, her dyspnea persisted. Progressive bronchiectasis was seen on HRCT, predominantly in the lower lobes. A pulmonary function test showed mixed impairment. We made a diagnosis of bronchiolitis obliterans after chronic graft versus host disease (GVHD). Prednisolone and an increased dose of tacrolimus (FK506) were administered, but type II respiratory failure progressed and she died 2 months after admission. On HRCT, each lobe was graded for bronchiectasis using a scale: 0 = normal, 1 = less than 2 x the diameter of an adjacent pulmonary artery, 2 = 2 - 3 x the diameter of an adjacent pulmonary artery, and 3 = more than 3 x the diameter of an adjacent pulmonary artery. A total score was calculated by summing the scores of all the lobes (maximum 15). In this case, the total score increased rapidly from 0 to 13 in 2 months.

Topics: Bronchiectasis; Bronchiolitis Obliterans; Chronic Disease; Disease Progression; Fatal Outcome; Female; Graft vs Host Disease; Humans; Middle Aged; Peripheral Blood Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Respiratory Insufficiency; Severity of Illness Index; Tacrolimus; Tomography, X-Ray Computed; Transplantation, Homologous

Topics: Adult; Antiviral Agents; Critical Care; Diagnosis, Differential; Disease Outbreaks; Drug Resistance, Viral; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Immunosuppressive Agents; Influenza A Virus, H1N1 Subtype; Influenza, Human; Intensive Care Units; Kidney Failure, Chronic; Liver Cirrhosis; Liver Transplantation; Opportunistic Infections; Oseltamivir; Postoperative Complications; Prednisone; Respiratory Insufficiency; Tacrolimus

A 74-year-old woman was experiencing rheumatoid arthritis complicated with interstitial pneumonitis (IP), and tacrolimus treatment was started. She presented with dyspnea. Chest X-ray and computed tomography (CT) showed ground-glass opacity and IP. Although tacrolimus was stopped, she died of respiratory failure. At autopsy, both the upper and lower lung fields showed usual IP and the organizing stage of diffuse alveolar damage. The former is common, but the latter is uncommon, suggesting tacrolimus may cause severe alveolar damage.

Topics: Aged; Arthritis, Rheumatoid; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Respiratory Insufficiency; Tacrolimus

The tuberculostatic compound rifampin (INN, rifampicin) induces the expression of a number of drug metabolism-related genes involved in multidrug resistance (P-glycoprotein and multidrug resistance proteins 1 and 2), cytochromes (cytochrome P450 [CYP] 3A4), uridine diphosphate-glucuronosyltransferases, monoamine oxidases, and glutathione S -transferases. Drugs that depend on these enzymes for their metabolism are prone to drug interactions when coadministered with rifampin. A novel, clinically relevant drug interaction is described between rifampin and mycophenolate mofetil (MMF), a cornerstone immunosuppressive molecule used in solid organ transplantation. Long-term rifampin therapy caused a more than twofold reduction in dose-corrected mycophenolic acid (MPA) exposure (dose-interval area under the concentration curve from 0 to 12 hours [AUC 0-12]) when administered simultaneously in a heart-lung transplant recipient, whereas subsequent withdrawal of rifampin resulted in reversal of these changes after 2 weeks of washout (dose-corrected AUC 0-12 after rifampin withdrawal, 19.7 mg.h.L-1.g -1 versus 6.13 mg.h.L-1.g-1 before rifampin withdrawal [221% change]; dose-uncorrected AUC 0-12 after rifampin withdrawal, 29.6 mg.h/L [daily MMF dose, 3 g] versus 18.4 mg.h/L [daily MMF dose, 6 g] during rifampin administration [60.8% change]). Failure to recognize this drug interaction could potentially lead to MPA underexposure and loss of clinical efficacy. The effect of rifampin on MPA metabolism can, at least in part, be explained by simultaneous induction of renal, hepatic, and gastrointestinal uridine diphosphate-glucuronosyltransferases and organic anion transporters with subsequent functional inhibition of enterohepatic recirculation of MPA.

Topics: Area Under Curve; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Enterohepatic Circulation; Glucuronosyltransferase; Heart-Lung Transplantation; Histiocytosis, Langerhans-Cell; Humans; Hypertension, Pulmonary; Male; Metabolic Clearance Rate; Middle Aged; Mycophenolic Acid; Pharmacology, Clinical; Respiratory Insufficiency; Rifampin; Tacrolimus; Time Factors; Uridine Diphosphate; Withholding Treatment