1,234 results on '"Mycophenolic acid"'
Search Results
2. Everolimus Use in Lung Transplant Recipients
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Sinan, Turkkan, Fatmanur Celik, Basaran, Mehmet Furkan, Sahin, Muhammet Ali, Beyoglu, Emre, Yilmaz, Hülya Yigit, Ozay, Mustafa, Bindal, Alkin, Yazicioglu, and Erdal, Yekeler
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Graft Rejection ,Transplantation ,Graft Survival ,Humans ,Drug Therapy, Combination ,Surgery ,Everolimus ,Mycophenolic Acid ,Kidney Transplantation ,Lung ,Tacrolimus ,Immunosuppressive Agents ,Transplant Recipients - Abstract
Most lung transplantation centers prefer triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. However, to prevent complications and comorbidities caused by tacrolimus, replacing the drug with everolimus has been considered.This is a retrospective observational study investigating everolimus switch for different reasons. The population was divided into 3 groups: chronic lung allograft dysfunction (CLAD), kidney impairment, and malignant neoplasm groups. We investigated whether we achieved the goal of the switch and the frequency of rejection, cytomegalovirus and fungal infections, and everolimus adverse effects.Nineteen patients received everolimus therapy, and 5 of these were for CLAD, 7 for tacrolimus nephrotoxicity, and 7 for explant/de novo malignant neoplasm. The patients were followed up for a mean (SD) of 30 (16.7) months under the therapy. The number of acute cellular rejection, cytomegalovirus infection, and aspergillosis infection cases before switch were 7, 13, and 2, respectively, and 7, 2, and 3 after that. The mean values of creatinine and estimated glomerular filtration rate of the whole population after the switch improved with no statistical significance, whereas it was significant in tacrolimus nephrotoxicity group. Three patients in the CLAD group remained stable after switching, whereas 2 progressed. Only 1 of the 7 patients with malignant neoplasms had a recurrence during 31.1 (16.5) months of median follow-up. Eleven cases of everolimus adverse effects occurred in 9 patients (47.3%), with 2 (10.5%) withdrawal events. Kidney impairment (P = .02) and age (P = .05) stood out as significant risk factors for drug adverse effects.After lung transplant, everolimus can be a safe alternative for immunosuppression with acceptable adverse effects.
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- 2022
3. Suspected Pneumonia Caused by Coronavirus Disease 2019 After Kidney Transplantation: A Case Report
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Kana Kano, Makoto Toguchi, Shoichi Iida, Eri Sekido, Hiroshi Toma, Tomokazu Shimizu, Taiji Nozaki, Kazuya Omoto, Toshihide Horiuchi, Shinya Kato, Masashi Inui, Toshio Takagi, and Yu Kijima
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Male ,Pediatrics ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Exacerbation ,Population ,law.invention ,law ,Full Length Article ,medicine ,Humans ,Infection control ,COVID-19 pneumonia ,education ,Kidney transplantation ,Aged ,Transplantation ,education.field_of_study ,Lung ,SARS-CoV-2 ,business.industry ,Sodium ,acute respiratory distress syndrome (ARDS) ,Anticoagulants ,COVID-19 ,Pneumococcal pneumonia ,Mycophenolic Acid ,medicine.disease ,Kidney Transplantation ,Intensive care unit ,Pneumonia ,medicine.anatomical_structure ,Surgery ,business - Abstract
Background Coronavirus disease 2019 (COVID-19) infection may become more severe in those who have undergone kidney transplantation than in the general population. False-negative reverse transcription-polymerase chain reaction (RT-PCR) results have been reported for COVID-19 infection. Patients might carry infection even though RT-PCR results are negative. Case report A 65-year-old man with a 19-year history of ABO-incompatible kidney transplantation presented with fever and arthralgia. Although the RT-PCR result was negative, a focal slit-glass shadow in the left upper lobe on computed tomography (CT) suggested COVID-19 pneumonia. His symptoms did not improve until after 10 days, and CT showed multiple slit-glass shadows in the bilateral lung fields. However, RT-PCR remained negative. The patient was admitted, and mycophenolate mofetil was discontinued. Anticoagulants were administered on the third day of hospitalization. Because of poor oxygenation, the patient was intubated in the intensive care unit on the fifth day, and sivelestat sodium was administered. The patient was extubated on the 12th day after improvement in oxygenation. There was no exacerbation, and CT showed improvements on day 51. Conclusion We report a case of pneumonia with suspected COVID-19 infection 18 years after living donor kidney transplantation. If COVID-19 is suspected, infection control and aggressive therapeutic interventions should be undertaken while considering the possibility of a positive result.
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- 2022
4. Hepatic Angiosarcoma Post-Renal Transplantation: A Case Report
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Show-Hwa, Tong, Yen-Ju, Huang, Yung-Cheng, Yang, Hui-Chuan, Lin, and Yeong-Chin, Jou
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Transplantation ,Tea ,Hemangiosarcoma ,Liver Neoplasms ,Humans ,Female ,Surgery ,Everolimus ,Middle Aged ,Mycophenolic Acid ,Kidney Transplantation ,Immunosuppressive Agents ,Tacrolimus - Abstract
DNA damage and oncogenic viruses increase the risk of cancer post-kidney transplantation, including skin cancer, Kaposi's sarcoma, oral cancer, and non-Hodgkin lymphoma. Here we report an uncommon case of liver angiosarcoma that occurred 8 years after kidney transplantation. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source.A 57-year-old female patient received a cadaver kidney transplantation 8 years ago. She followed a long-term regimen of tacrolimus, mycophenolate sodium, and everolimus, with good renal function. She received annual regular abdominal ultrasound examinations after kidney transplantation, which showed no findings. The patient suffered from several symptoms for approximately 2 weeks before a scheduled abdominal ultrasound: diarrhea, epigastric pain, abdominal fullness, tea-colored urine, and little stool passage. The abdominal computerized tomography showed multiple hepatic tumors in both the hepatic lobes with engorged vasculatures and mild hemoperitoneum. A liver biopsy revealed the histopathology of angiosarcoma. The patient suffered multiple organ failure within one month of treatment.Various post-transplant malignancies are not uncommon after transplantation, warranting periodic screenings for any symptoms in these patients.
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- 2022
5. Mycophenolate mofetil as a treatment of severe steroid-resistant immune-related hepatitis
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Alberto Fernández Villaverde, Lucia Santomé Couto, Cristina Macía-Rodríguez, Javier de la Fuente Aguado, and Carlos Romero Reinoso
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Hepatitis ,Hepatology ,business.industry ,Gastroenterology ,MEDLINE ,Mycophenolic Acid ,Mycophenolate ,medicine.disease ,Steroid resistant ,Treatment Outcome ,Immune system ,Immunology ,medicine ,Humans ,Steroids ,Nivolumab ,business ,Immunosuppressive Agents - Published
- 2022
6. Case Report of COVID-19 Infection After Kidney Transplant Treated With Casirivimab-Imdevimab and Mycophenolate Mofetil Changed to Everolimus
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Yu Kijima, Tomokazu Shimizu, Shinya Kato, Kana Kano, Toshihide Horiuchi, Taiji Nozaki, Kazuya Omoto, Masashi Inui, Hiroshi Toma, Shoichi Iida, and Toshio Takagi
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Graft Rejection ,Male ,kidney transplant ,Transplantation ,Heparin ,SARS-CoV-2 ,Antibodies, Monoclonal ,COVID-19 ,Middle Aged ,Mycophenolic Acid ,Antibodies, Monoclonal, Humanized ,everolimus ,Kidney Transplantation ,Methylprednisolone ,Tacrolimus ,Article ,monoclonal antibody ,Creatinine ,Humans ,Surgery ,Immunosuppressive Agents - Abstract
Background Casirivimab-imdevimab is a cocktail of two monoclonal antibodies designed to prevent infection by SARS-CoV-2, the virus that causes COVID-19. Casirivimab-imdevimab has been approved in Japan for treating mild to moderate coronavirus disease (COVID-19); however, to the best of our knowledge, there are no reports of its use after kidney transplantation from a live donor. Everolimus, antineoplastic chemotherapy drug, is expected to be effective in inhibiting the spread of SARS-CoV-2 and preventing its replication, which may facilitate treatment. Here, we report a case of COVID-19 infection following kidney transplantation, that was initially treated with casirivimab-imdevimab and mycophenolate mofetil, but was later changed to everolimus. Case report A 47-year-old man underwent living donor kidney transplantation from his mother in 2017. Immunosuppression therapy was underway through the administration of tacrolimus, mycophenolate mofetil, and methylprednisolone. In early September 2021, he was diagnosed with COVID-19 and was hospitalized on Day 3 (Table 1). On hospitalization, mycophenolate mofetil was discontinued and casirivimab-imdevimab and heparin were started. The patient was started on everolimus on Day 5. The clinical course was successful without rejection (Fig. 1). There was no exacerbation of COVID-19; the patient's serum creatinine levels and renal function had otherwise remained stable. Conclusion We could safely treat a patient with casirivimab-imdevimab after kidney transplantation. It is suggested that casirivimab-imdevimab can prevent COVID-19 from becoming severe and can be administered without worsening renal function. In addition, everolimus may have inhibited the spread of the virus and prevented it from replicating.
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- 2022
7. Recurrent Cytomegalovirus Infection Controlled by the Introduction of Everolimus in a Simultaneous Pancreas-Kidney Transplantation Recipient: A Case Report
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Hajime Imamura, Tomohiko Adachi, Takayuki Tanaka, Hajime Matsushima, Takanobu Hara, Akihiko Soyama, Masaaki Hidaka, and Susumu Eguchi
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Graft Rejection ,Male ,Transplantation ,TOR Serine-Threonine Kinases ,Graft Survival ,Middle Aged ,Mycophenolic Acid ,Kidney Transplantation ,Tacrolimus ,Colony-Stimulating Factors ,Cytomegalovirus Infections ,Humans ,Valganciclovir ,Surgery ,Everolimus ,Pancreas Transplantation ,Viremia ,Pancreas ,Immunosuppressive Agents - Abstract
In simultaneous pancreas-kidney transplantation (SPK) recipients, cytomegalovirus (CMV) infection is a major complication that has been associated with the use of tacrolimus (TAC)-based immunosuppression. As one of the immunosuppressive drug options, the use of mammalian target of rapamycin inhibitors (mTORi) results in reduced rates of CMV infection in the field of solid organ transplantation. However, little is known about mTORi usage in pancreas transplantation. We report a case of recurrent CMV infection that was controlled by the introduction of mTORi (everolimus) in addition to a TAC-based immunosuppression regimen in SPK. A 52-year-old man underwent SPK. Graft duodenal perforation occurred on the 13th day of surgery, and graft duodenal resection was performed after long-term abscess drainage treatment. After graft duodenal resection, he was diagnosed with CMV viremia, and valganciclovir was started. However, because of recurrent febrile neutropenia caused by cytopenia as a side effect of valganciclovir, there was a repeated need for granulocyte-colony stimulating factor treatment. Immunosuppressive drug taper adjustment was attempted to control recurrent CMV viremia, and everolimus was introduced with the aim of reducing the dose of TAC and mycophenolate mofetil. This resulted in a continuously negative CMV antigenemia test and a stable general condition. Understanding the characteristics of various immunosuppressive agents and appropriately controlling and managing infectious diseases is crucial for the good postoperative management of patients with SPK.
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- 2022
8. Acute Anti-A/B Antibody-Mediated Rejection After ABO-Incompatible Kidney Transplantation Treated With Bortezomib and Plasmapheresis: A Case Report
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Jin Ho Lee, Heeryong Lee, Kipyo Kim, Seoung Woo Lee, Joon Ho Song, and Seun Deuk Hwang
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Bortezomib ,Graft Rejection ,Male ,Transplantation ,Blood Group Incompatibility ,Humans ,Surgery ,Plasmapheresis ,Middle Aged ,Mycophenolic Acid ,Kidney Transplantation ,Immunosuppressive Agents ,ABO Blood-Group System - Abstract
ABO-incompatible kidney transplantation (KTP) is effective for avoiding transplantation-related issues. It is a viable alternative to ABO-compatible KTP, as both techniques have similar patient and graft survival rates. However, anti-A/B antibody-mediated rejection (AMR) can occur, resulting in poor long-term graft survival.A 45-year-old man with end-stage renal disease presented with a serum creatinine level of 10.2 mg/dL. We decided to perform KTP with spousal donation. He had panel-reactive antibody class I and II and cross matching test negativity, a 3/6 mismatch on human leukocyte antigen typing, an ABO antibody titer of 1:256, and no donor-specific antibodies. The patient and donor blood types were O+ and A+, respectively. The anti-A/B antibody titer was reduced preoperatively with rituximab (200 mg/body), plasmapheresis, and intravenous immunoglobulin (0.2 mg/kg). Basiliximab and methylprednisolone were used for induction immunosuppression, and tacrolimus, mycophenolate mofetil, and prednisolone were used for maintenance immunosuppression. KTP was successful, and graft function was initially normal. On postoperative day (POD) 5, the serum creatinine level and anti-A/B antibody titer increased from 0.9 mg/dL to 1.9 mg/dL and 1:16 to 1:64, respectively. Graft biopsy revealed acute AMR and tubular injury. We started steroid pulse therapy, plasmapheresis, and subcutaneous bortezomib (2.6 mg, twice a day, every 3 days) with no side effects. The serum creatinine level decreased from 5.7 mg/dL to 1.5 mg/dL on POD 28. Graft biopsy showed no rejection, and normal function was maintained for 40 months.Acute, early anti-A/B AMR was successfully treated with plasmapheresis and bortezomib.
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- 2022
9. Effectiveness of T cell–mediated rejection therapy: A systematic review and meta-analysis
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Chris Wiebe, Ahmed M Abou-Setta, Peter Nickerson, Aaron J. Trachtenberg, Otto L T Lam, Viraj K Reddy, Rasheda Rabbani, Julie Ho, Christie Rampersad, Nicole Askin, and George N. Okoli
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Graft Rejection ,Transplantation ,medicine.medical_specialty ,business.industry ,T-Lymphocytes ,Incidence (epidemiology) ,medicine.medical_treatment ,MEDLINE ,Immunosuppression ,CINAHL ,Mycophenolic Acid ,Kidney Transplantation ,Tacrolimus ,Confidence interval ,Clinical trial ,Study heterogeneity ,Internal medicine ,Meta-analysis ,Humans ,Immunology and Allergy ,Medicine ,Pharmacology (medical) ,business ,Immunosuppressive Agents - Abstract
The effectiveness of T cell-mediated rejection (TCMR) therapy for achieving histological remission remains undefined in patients on modern immunosuppression. We systematically identified, critically appraised and summarized the incidence and histological outcomes after TCMR treatment in patients on tacrolimus (Tac) and mycophenolic acid (MPA). English-language publications were searched in MEDLINE (Ovid), Embase (Ovid), Cochrane Central (Ovid), CINAHL (EBSCO), Clinicaltrials.gov (NLM) up to January 2021. Study quality was assessed with National Institutes of Health Study Quality Tool. We pooled results using an inverse variance, random-effects model and report the binomial proportions with associated 95% confidence intervals (95% CI). Statistical heterogeneity was explored using the I2 statistic. From 2,875 screened citations, we included 12 studies (1,255 participants). Fifty-eight percent were good/high quality while the rest were moderate quality. Thirty-nine percent of patients (95%CI 0.26-0.53, I2 77%) had persistent ≥Banff Borderline TCMR 2-9 months after anti-rejection therapy. Pulse steroids and augmented maintenance immunosuppression were mainstays of therapy, but considerable practice heterogeneity was present. A high proportion of biopsy-proven rejection exists after treatment emphasizing the importance of histology to characterize remission. Anti-rejection therapy is foundational to transplant management but well-designed clinical trials in patients on Tac/MPA immunosuppression are lacking to define the optimal therapeutic approach.
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- 2022
10. Japanese Single-Center Experience of Kidney Transplant: Experience in a Japanese Private Hospital
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Tomokazu Shimizu, Shinya Kato, Yu Kijima, Kana Kano, Toshihide Horiuchi, Shoichi Iida, Kazuya Omoto, Masashi Inui, Taiji Nozaki, and Hiroshi Toma
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Graft Rejection ,Male ,Transplantation ,Middle Aged ,Mycophenolic Acid ,Kidney Transplantation ,Tacrolimus ,Hospitals, Private ,Basiliximab ,Japan ,Humans ,Female ,Surgery ,Immunosuppressive Agents - Abstract
We reviewed the results of cases of kidney transplant (KTx) that were conducted at the Toda Chuo General Hospital, a private hospital located in Saitama, Japan.A total of 312 patients with end-stage renal failure underwent KTx between January 1992 and December 2019 at Toda Chuo General Hospital. There were 191 men and 121 women. Their mean age was 45.7 years. Of the 312 cases, 310 were living-related KTx, while 2 were deceased donor KTx. The immunosuppressive treatment protocol mainly consisted of 4-drug therapy with methylprednisolone, tacrolimus, mycophenolate mofetil, and basiliximab.Patient survival was 99.7% at 1 year, 99.3% at 5 years, and 97.3% at 10 years. Renal allograft survival was 98.4% at 1 year, 91.7% at 5 years, and 86.5% at 10 years. However, death-censored renal allograft survival was 98.7% at 1 year, 92.4% at 5 years, and 89.0% at 10 years. Among the 312 patients, 33 grafts were lost during the observation period. The loss was because of chronic antibody-mediated rejection in 19 patients, death with function in 6 patients, and acute antibody-mediated rejection in 2 patients.The prognosis of patients and their grafts, which were managed following the immunosuppression protocol at our institute, was relatively good. KTx in a private hospital in Japan is at par with the global standard.
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- 2022
11. Comparison of free plasma versus saliva mycophenolic acid exposure following mycophenolate mofetil administration in adult kidney transplant recipients
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Christine E. Staatz, A. Cossart, Gillian Gorham, and Katherine A. Barraclough
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Adult ,Male ,Drug ,Saliva ,media_common.quotation_subject ,Clinical Biochemistry ,Pharmacology ,Mycophenolate ,Kidney transplant ,Mycophenolic acid ,medicine ,Humans ,Kidney transplantation ,Aged ,media_common ,business.industry ,General Medicine ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Kidney Transplantation ,Therapeutic monitoring ,Transplantation ,stomatognathic diseases ,Female ,Drug Monitoring ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Therapeutic monitoring (TDM) of mycophenolic acid (MPA) has the potential to improve drug inefficacy and toxicities in kidney transplantation. However, measurement of plasma MPA concentrations is laborious and invasive. This study examined the utility of saliva compared with plasma based TDM of MPA. Paired blood and saliva samples were collected from 47 adult kidney transplant recipients pre- and at 1-, 2-, and 4-hours post mycophenolate mofetil administration. No relationship was observed between saliva MPA concentrations and either total or free plasma MPA concentrations (p > 0.05). This suggests that saliva is a poor direct marker of plasma MPA concentrations and therefore should not be used for MPA TDM.
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- 2022
12. Results of the RENAISSANCE Study: REsponse to BNT162b2 COVID-19 vacciNe—short- And long-term Immune reSponSe evAluatioN in health Care workErs
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Marco Merli, Valeria Cento, Matteo Corradin, Irene Cuppari, Nicola Ughi, Federica Di Ruscio, Michele Senatore, Daniela Campisi, Alessandra Romandini, Paolo Andrea Schenardi, Roberto Crocchiolo, Marco Bosio, Chiara Vismara, Massimo Puoti, Simona Giroldi, Silvano Rossini, Laura Zoppini, Francesco Scaglione, Mauro Moreno, Oscar Massimiliano Epis, Oscar Matteo Gagliardi, Arianna Pani, Pani, A, Cento, V, Vismara, C, Campisi, D, Di Ruscio, F, Romandini, A, Senatore, M, Schenardi, P, Gagliardi, O, Giroldi, S, Zoppini, L, Moreno, M, Corradin, M, Epis, O, Ughi, N, Cuppari, I, Crocchiolo, R, Merli, M, Bosio, M, Rossini, S, Puoti, M, and Scaglione, F
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medicine.medical_specialty ,biology ,business.industry ,General Medicine ,Mycophenolic acid ,Serology ,Vaccination ,Titer ,COVID-19, SARS-CoV-2, Vaccine ,Immune system ,Interquartile range ,Internal medicine ,medicine ,biology.protein ,Clinical endpoint ,Antibody ,business ,medicine.drug - Abstract
Objective: To evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike (S) IgG antibody production after vaccination with BNT162b2 and the protection from symptomatic breakthrough infections in health care workers. Methods: This prospective observational study (RENAISSANCE) had as a primary end point the evaluation of serologic response to BNT162b2 14 days after a second dose. SARS-CoV-2 anti-S IgG antibodies were evaluated with LIAISON SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A.), which is able to detect the presence of both binding and neutralizing antibodies for trimeric spike glycoprotein. Participants were recruited from February 1, 2021, to February 22, 2021. Occurrence of vaccine breakthrough infections was assessed by reverse transcription–polymerase chain reaction on symptomatic and contact cases up to June 6, 2021. Results: Of 2569 staff evaluated, only 4 were nonresponders (0.16%; 95% CI, 0.04% to 0.41%). All 4 nonresponders were severely immunosuppressed and receiving treatment with mycophenolate mofetil or mycophenolic acid. At 14 days after the second dose, 67.5% (1733) of staff had anti-S IgG titers of 2000 BAU/mL or higher; 19.2% (494), between 1500 and 2000 BAU/mL; 9.8% (251), between 1000 and 1500 BAU/mL; and 3.4% (87), 1000 BAU/mL or lower. Women had a higher probability of having higher titers than men (64.5% [1044/1618] vs 58.3% [410/703]; P=.005). This was confirmed after adjustment for age group (odds ratio, 1.275; 95% CI, 1.062 to 1.531; P=.009). Four months after the end of the vaccination program, only 13 participants (0.26%) had experienced a breakthrough SARS-CoV-2 infection, including 1 nonresponder. This was the only participant requiring hospitalization for severe COVID-19. Conclusion: The vaccination campaign among health care workers at the ASST GOM Niguarda has resulted in a marked serologic response and reduction of incident COVID-19 cases. Yet, the lack of protection should not be overlooked in immunocompromised individuals.
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- 2021
13. Weak antibody response to three doses of mRNA vaccine in kidney transplant recipients treated with belatacept
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Carole Burger, Christophe Legendre, Anne Scemla, Marianne Leruez-Ville, Fanny Lanternier, Nathalie Chavarot, Dany Anglicheau, Antoine Morel, Lucile Amrouche, L Bererhi, Frank Martinez, Alexandra Serris, Rebecca Sberro-Soussan, Gillian Divard, Julien Zuber, and Estelle Vilain
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Male ,medicine.medical_specialty ,COVID-19 Vaccines ,Belatacept ,Gastroenterology ,Kidney transplant ,Mycophenolic acid ,Abatacept ,Seroepidemiologic Studies ,Internal medicine ,Humans ,Immunology and Allergy ,Medicine ,Seroprevalence ,Pharmacology (medical) ,Aged ,Vaccines, Synthetic ,Transplantation ,SARS-CoV-2 ,business.industry ,Immunogenicity ,Antibody titer ,COVID-19 ,Middle Aged ,Kidney Transplantation ,Vaccination ,Antibody response ,Antibody Formation ,business ,medicine.drug - Abstract
Poor responses to mRNA COVID-19 vaccine have been reported after 2 vaccine injections in kidney transplant recipients (KTRs) treated with belatacept. We analyzed the humoral response in belatacept-treated KTRs without a history of SARS-CoV-2 infection who received three injections of BNT162b2-mRNA COVID-19 vaccine. We also investigated vaccine immunogenicity in belatacept-treated KTRs with prior COVID-19 and characterized symptomatic COVID-19 infections after the vaccine in belatacept-treated KTRs. Among the 62 belatacept-treated KTRs (36 [58%] males), the median age (63.5 years IQR [51-72]), without COVID-19 history, only four patients (6.4%) developed anti-SARS-CoV-2 IgG with low antibody titers (median 209, IQR [20-409] AU/ml). 71% were treated with mycophenolic acid and 100% with steroids in association with belatacept. In contrast, in all the 5 KTRs with prior COVID-19 history, mRNA vaccine induced a strong antibody response with high antibody titers (median 10 769 AU/ml, IQR [6410-20 069]) after two injections. Seroprevalence after three-vaccine doses in 35 non-belatacept-treated KTRs was 37.1%. Twelve KTRs developed symptomatic COVID-19 after vaccination, including severe forms (50% of mortality). Breakthrough COVID-19 occurred in 5% of fully vaccinated patients. Administration of a third dose of BNT162b2 mRNA COVID-19 vaccine did not improve immunogenicity in KTRs treated with belatacept without prior COVID-19. Other strategies aiming to improve patient protection are needed.
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- 2021
14. Edema Associated With Everolimus de Novo
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Catuxa Rodríguez Magariños, María Calvo Rodríguez, Tamara Ferreiro Hermida, Leticia García Gago, Ángel Alonso Hernández, Constantino Fernández Rivera, Andrés López Muñiz, and Daniela Astudillo Jarrín
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Graft Rejection ,medicine.medical_specialty ,medicine.medical_treatment ,Renal function ,Group A ,Gastroenterology ,Tacrolimus ,Mycophenolic acid ,Group B ,Edema ,Internal medicine ,medicine ,Humans ,Everolimus ,Kidney transplantation ,Transplantation ,business.industry ,Graft Survival ,Immunosuppression ,Mycophenolic Acid ,medicine.disease ,Surgery ,medicine.symptom ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Background The appearance of edema limits the use of everolimus de novo together with tacrolimus and steroids in kidney transplantation. We aimed to investigate the frequency and characteristics of patients with edema and compare them according to the type of immunosuppression. Methods We studied 150 kidney transplant recipients between 2015 and 2017 based on receiving everolimus de novo (group A) or mycophenolic acid derivatives (group B). Results We analyzed 50 patients in group A and 100 in group B. Follow-up was 26.2 ± 10 months. Fifty-six patients presented edema (37.3%): 54% in group A and 29% in group B (P = .003). Edema was mild in 74% of patients in group A and 57.1% in group B. The probability of edema was 10.1%, 22.4%, and 41% at 3, 6, and 12 months, respectively, in group A vs 10.1%, 20.3%, and 25.4% in group B (P = .006). Patients were treated mostly with diuretics (14.3% in group A vs 27.6% in group B) and discontinuation of calcium channel blockers (46.4% in group A vs 48.3% in group B). Improvement was 70.4% in group A vs 60.7% in group B; patient worsening was 0% in group A vs 10.7% in group B; and there was no change in 29.6% in group A vs 28.6% in group B. We did not find differences in patient or graft survival in those who presented edema, regardless of the treatment group. Conclusion The use of everolimus and standard doses of tacrolimus caused edema in 54% of patients, with no impact on renal function or survival compared with mycophenolic acid derivatives. The edema was mostly of low intensity and improved in most patients.
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- 2021
15. 75-Year-Old Man With Fever and Malaise
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Katrina A. Williamson, Alí Duarte-García, and Jeffrey X. Yang
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Male ,medicine.medical_specialty ,business.industry ,General surgery ,Remission Induction ,General Medicine ,Acute Kidney Injury ,Immunologic Tests ,Mycophenolic Acid ,Prognosis ,Lupus Nephritis ,Methylprednisolone ,Malaise ,Diagnosis, Differential ,Pleural Effusion ,Renal Dialysis ,Antirheumatic Agents ,Humans ,Lupus Erythematosus, Systemic ,Medicine ,medicine.symptom ,business ,Immunosuppressive Agents ,Aged ,Hydroxychloroquine - Published
- 2021
16. Time to Uveitis Control with Methotrexate and Mycophenolate Mofetil
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Anh D. Bui, Christina L. Kong, Nicole K. Kelly, S.R. Rathinam, John A. Gonzales, Radhika Thundikandy, Anuradha Kanakath, Bala Murugan, R. Vedhanayaki, Lyndell L. Lim, Eric B. Suhler, Hassan A. Al-Dhibi, Thuy Doan, and Nisha R. Acharya
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Uveitis ,Ophthalmology ,Methotrexate ,Humans ,Mycophenolic Acid ,Immunosuppressive Agents - Published
- 2022
17. Variants in mycophenolate and CMV antiviral drug pharmacokinetic and pharmacodynamic genes and leukopenia in heart transplant recipients
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RobertL. PageII, Kris Oreschak, Christina L. Aquilante, JoAnn Lindenfeld, Kimberly M. Deininger, Laura Saba, Amrut V. Ambardekar, and Nicholas Rafaels
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Graft Rejection ,Male ,Pulmonary and Respiratory Medicine ,Ganciclovir ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Congenital cytomegalovirus infection ,Cytomegalovirus ,030230 surgery ,Mycophenolate ,Antiviral Agents ,Polymorphism, Single Nucleotide ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Hepatocyte Nuclear Factor 1-alpha ,Retrospective Studies ,Heart transplantation ,Transplantation ,Antibiotics, Antineoplastic ,Leukopenia ,business.industry ,Valganciclovir ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Transplant Recipients ,Pharmacogenomic Testing ,Heart Transplantation ,Female ,030211 gastroenterology & hepatology ,Surgery ,Antiviral drug ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Pharmacogenetics ,Follow-Up Studies ,medicine.drug - Abstract
BACKGROUND: The objective was to assess the relationship between single nucleotide polymorphisms in mycophenolate and cytomegalovirus antiviral drug pharmacokinetic and pharmacodynamic genes and drug-induced leukopenia in adult heart transplant recipients. METHODS: This retrospective analysis included N=148 patients receiving mycophenolate and a cytomegalovirus antiviral drug. In total, 81 single nucleotide polymorphisms in 21 pharmacokinetic and 23 pharmacodynamic genes were selected for investigation. The primary and secondary outcomes were mycophenolate and/or cytomegalovirus antiviral drug-induced leukopenia, defined as a white blood cell count C (p.I27L) was associated with drug-induced leukopenia (unadjusted p=0.002; false discovery rate
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- 2021
18. Health- and Vision-Related Quality of Life in a Randomized Controlled Trial Comparing Methotrexate and Mycophenolate Mofetil for Uveitis
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Nicole K. Kelly, Aheli Chattopadhyay, S.R. Rathinam, John A. Gonzales, Radhika Thundikandy, Anuradha Kanakath, S. Bala Murugan, R. Vedhanayaki, Dean Cugley, Lyndell L. Lim, Eric B. Suhler, Hassan A. Al-Dhibi, Caleb D. Ebert, Elyse J. Berlinberg, Travis C. Porco, Nisha R. Acharya, A.L. Sivarama Subramanian, G. Jeyakohila, Gracy Evangelin, A.M. Azhagupandi, C.V. Praba, S. Bharati, S. Gomathi, N.J. Nirmaladevi, Mohammed Siddiq, B. Vijayakumar, S.R. Devi, V.R. Saravanan, Upendra Babu, R. Srija, S. Dhanalakshmi, R.R. Sakthimari, P.S. Keerthana, A.M. Mallika, C. Vasanthi, P.B. Mariselvi, P. Pandeeswari, S.M. Sudarvanitha, R. Prema, Prabu Baskaran, S. Madanagopalan, Chokkahalli K. Nagesha, R. Thilagavathi, Chitra Krishnakumari, Irudhaya Raj P, S. Saravanan, Grace Mary, S. Nagarasi, Kiruba Gnansi, Lourdes Arellanes-Garcia, Luz Elena Concha del Rio, Rashel Cheja Kalb, Nancy Fernández, Yoko Burgoa, Hilda Hernández, Roberto Fabela Cuello, Lorenzo Agustín Martínez Garcia, Ricardo Montoya Rodríguez, Maria del Carmen Preciado, Andrea Arreola, Donald Stone, Mohammed Al-Shamrani, Sara Al-Nuwaysir, Abdulrahman Al-Hommadi, Abdullah Al-Omran, Saleh Al-Nasser, Gahram Al-Zahrani, Eman Mashan, Mizher Al-Ghamdi, Ayshah Al-Tuwejri, Debra A. Goldstein, Anna Liza Castro-Malek, Gemma Dela Rosa, Marriner Skelly, Eric Suhler, James Rosenbaum, Phoebe Lin, Sherveen Salek, Kristin Biggee, Amde Shifera, Laura Kopplin, George Mount, Tracy Giles, Susan Nolte, Ann Lundquist, Teresa Liesegang, Albert Romo, Chris Howell, Scott Pickell, Peter Steinkemp, Dawn Ryan, Jordan Barth, Jocelyn Hui, Chiedozie Ukachukwu, Lyndell Lim, Richard Stawell, Robyn Troutbeck, Cecilia Ling, Xavier Fagan, Julian Bosco, Timothy Godfrey, Tanya Pejnovic, Carly D’Sylva, Sutha Sanmugasundram, Tina-Marie van Tonder, Maria Kolic, Nisha Acharya, John Gonzales, Thuy Doan, Sarah Lopez, Maya Rao, Erica Browne, Betty Hom, Mary Lew, Salena Lee, Travis Porco, Thomas Lietman, Jeremy Keenan, Eric Kim, Hieu Nguyen, Caleb Ebert, Elyse Berlinberg, Andrew Hirst, Rachel Weinrib, Maureen G. Maguire, William E. Barlow, Steven Yeh, Albert T. Vitale, Jaqueline J. Glover, Narsing A. Rao, and Donald F. Everett
- Subjects
Adult ,Male ,medicine.medical_specialty ,Visual acuity ,Health Status ,Administration, Oral ,Article ,law.invention ,Uveitis ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Randomized controlled trial ,Interquartile range ,law ,Sickness Impact Profile ,Surveys and Questionnaires ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Prospective Studies ,Enzyme Inhibitors ,Vision, Ocular ,Aged ,030304 developmental biology ,0303 health sciences ,business.industry ,Outcome measures ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,humanities ,Ophthalmology ,Methotrexate ,Health ,Quality of Life ,030221 ophthalmology & optometry ,Female ,medicine.symptom ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.Secondary analysis of a randomized controlled trial.Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests.Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months).Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively).Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.
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- 2021
19. Pharmacokinetics of Mycophenolate Mofetil Metabolites in Older Patients on the Seventh Day After Renal Transplantation
- Author
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M. Malec, Maria Chrzanowska, M. Głyda, and Joanna Sobiak
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medicine.medical_specialty ,Population ,Urology ,Renal function ,Reference range ,Mycophenolic acid ,Glucuronides ,Pharmacokinetics ,medicine ,Humans ,education ,Aged ,Volume of distribution ,Transplantation ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Mycophenolic Acid ,Kidney Transplantation ,Therapeutic drug monitoring ,Area Under Curve ,Surgery ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Background Currently, immunosuppression schemes are age-independent; however, physiological changes may alter drugs’ pharmacokinetics in the older population. We compared mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) pharmacokinetics among patients aged 60 years on the seventh day after renal transplantation. Methods We included 7 and 10 renal transplant recipients, aged >60 and Results In patients aged >60 years, mean MPA and MPAG concentrations before the next dose and ratio of MPAG area under the concentration-time curve (AUC0-12) to MPA AUC0-12 were higher by 1.6-fold, 1.4-fold, and 1.9-fold, respectively. Other MPAG concentrations appeared to be slightly higher (1.2- to 1.5-fold) in older patients. MPA apparent clearance was similar in both groups, whereas volume of distribution at steady state was slightly higher (1.6-fold) in patients aged >60 years. The variability of most MPA and some MPAG pharmacokinetics was greater in patients aged >60 years. The MPA AUC0-12 target was achieved in 40% and 14% of patients aged 60 years, respectively. The highest MPAG concentrations and AUC0-12 were observed for patients with the lowest glomerular filtration rate. Conclusions Higher variability of MPA and MPAG pharmacokinetic parameters, MPA AUC0-12 above the reference range, higher values of MPAG pharmacokinetics in patients with lower glomerular filtration rates, as well as lower proportion of patients achieving MPA targets all indicate the need for therapeutic drug monitoring in renal transplant recipients aged >60 years and to verify target MPA AUC0-12 for this population.
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- 2021
20. Diarrhea in a Patient With Combined Kidney-Pancreas Transplant
- Author
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Matthew A. Sparks, Krunal Amin, Vinay Choksi, and Samira S. Farouk
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Diarrhea ,Graft Rejection ,Male ,medicine.medical_specialty ,MEDLINE ,Gastroenterology ,Sapovirus ,Tacrolimus ,Diagnosis, Differential ,Feces ,Internal medicine ,Humans ,Medicine ,Glucocorticoids ,Caliciviridae Infections ,Kidney ,Drug Tapering ,business.industry ,Middle Aged ,Mycophenolic Acid ,Kidney Transplantation ,Gastroenteritis ,Diabetes Mellitus, Type 1 ,medicine.anatomical_structure ,Nephrology ,Disease Progression ,Fluid Therapy ,Kidney Failure, Chronic ,Prednisone ,Pancreas Transplantation ,medicine.symptom ,business ,Pancreas ,Multiplex Polymerase Chain Reaction ,Immunosuppressive Agents - Published
- 2021
21. Network meta-analysis–based comparison of first-line steroid-sparing adjuvants in the treatment of pemphigus vulgaris and pemphigus foliaceus
- Author
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Meng-Sui Lee, Tom C. Chan, Yi-Chun Yeh, and Yu-Kang Tu
- Subjects
Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Network Meta-Analysis ,Azathioprine ,Dermatology ,law.invention ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Recurrence ,law ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Cyclophosphamide ,Pemphigus foliaceus ,Randomized Controlled Trials as Topic ,integumentary system ,business.industry ,Pemphigus vulgaris ,Mycophenolic Acid ,medicine.disease ,Clinical trial ,Pemphigus ,030220 oncology & carcinogenesis ,Cyclosporine ,Drug Therapy, Combination ,Steroids ,Rituximab ,business ,Adjuvant ,medicine.drug - Abstract
Background Steroid-sparing adjuvants may enhance oral glucocorticoid benefits in pemphigus treatment. Selecting the optimal therapeutic option among various first-line steroid-sparing adjuvants is often a clinical challenge due to the lack of head-to-head clinical trials. Objective To determine the best first-line steroid-sparing adjuvants for pemphigus treatment. Methods Randomized controlled trials comparing different steroid-sparing adjuvants in patients with pemphigus were identified through a systematic literature search and subjected to a network meta-analysis. The primary outcomes were the proportion of remission and the mean cumulative glucocorticoid dose. Results Ten trials involving 592 patients were analyzed. Among the 7 steroid-sparing adjuvants evaluated, rituximab was the most effective for achieving remission and was more effective than steroid alone (odds ratio, 14.35; 95% confidence interval [CI], 4.71-43.68). Rituximab, azathioprine, and cyclophosphamide pulse therapy enabled the reduction of the cumulative glucocorticoid doses compared to the use of steroid alone: mean differences, −11,830.5 mg (95% CI, −14,089.48 to −9571.52), −3032.48 mg (−4700.74 to −1364.22), and −2469.54 mg (−4128.42 to −810.66), respectively. Limitations The results were driven primarily by a small number of studies, and the effect estimates are imprecise because of indirect comparisons. Conclusion Network meta-analysis showed that rituximab appears to be an efficacious, well tolerated steroid-sparing adjuvant for pemphigus.
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- 2021
22. Basiliximab With Delayed Tacrolimus Improves Short-Term Renal Outcomes Post-Liver Transplantation—a Real-World Experience
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James Neuberger, Peter Nightingale, Neil Rajoriya, M. Thamara P. R. Perera, Alexander Boyd, Jaimin Patel, James Ferguson, and Andrew Brown
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Basiliximab ,medicine.medical_treatment ,Liver transplantation ,Kidney ,urologic and male genital diseases ,Tacrolimus ,Postoperative Complications ,Adrenal Cortex Hormones ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Retrospective Studies ,Immunosuppression Therapy ,Transplantation ,business.industry ,Incidence ,Graft Survival ,Acute kidney injury ,Retrospective cohort study ,Immunosuppression ,Acute Kidney Injury ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Liver Transplantation ,Regimen ,Treatment Outcome ,Drug Therapy, Combination ,Female ,Surgery ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Background Acute kidney injury (AKI) is common after liver transplantation (LT). Induction with interleukin-2 receptor antagonists is often used as a “renal-sparing” strategy. The aim of this study was to assess this approach in a real-world setting in an LT center. Methods A retrospective cohort analysis of LTs between 2011 and 2018 was performed to assess the impact of a renal-sparing strategy using basiliximab in conjunction with mycophenolate mofetil and corticosteroids from day 0 post-LT along with delayed introduction of tacrolimus. This was compared with a group receiving tacrolimus, mycophenolate mofetil, and corticosteroids from the outset. Results The renal-sparing regimen was associated with significantly lower incidence of all-stage AKI at day 7 post-LT (36% vs 55%, P = .006) and less decline in renal function at 3 months (39% vs 57%, P = .01). No further significant differences in renal outcomes were observed at other time points on follow-up to 1 year post-LT. There was no significant difference in the incidence of acute cellular rejection, inpatient length of stay or graft survival. The decision to adopt a renal-sparing regimen was predominantly made on a clinically reactive basis within the first 24 hours post-LT in 77%, and was preordained in 23%. Cost-effectiveness analysis did not find evidence of a significant cost saving when using a renal-sparing strategy. Conclusion This study provides real-world analysis of the use of a renal-sparing immunosuppression regimen in LT. Although improvements in incidence of AKI in the short term were demonstrated, this did not translate to cost savings or improved renal outcomes after 3 months.
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- 2021
23. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial
- Author
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Dawn J. Caster, Ellen M. Ginzler, Laura Lisk, Robert B Huizinga, Brad H. Rovin, Cristina Arriens, Joshua Kaplan, Neil Solomons, Y K Onno Teng, Juanita Romero-Diaz, Keisha L. Gibson, Simrat Randhawa, Samir V. Parikh, and Sandra V. Navarra
- Subjects
Adult ,Male ,medicine.medical_specialty ,Calcineurin Inhibitors ,Lupus nephritis ,Renal function ,030204 cardiovascular system & hematology ,Placebo ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Double-Blind Method ,Prednisone ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Lupus Erythematosus, Systemic ,030212 general & internal medicine ,Glucocorticoids ,Aged ,business.industry ,General Medicine ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Lupus Nephritis ,Rheumatology ,Voclosporin ,Calcineurin ,Treatment Outcome ,chemistry ,Creatinine ,Cyclosporine ,Female ,business ,Glomerular Filtration Rate ,medicine.drug - Abstract
Background Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis.Methods This multicentre, double-blind, randomised phase 3 trial was done in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of systemic lupus erythematosus with lupus nephritis according to the American College of Rheumatology criteria, and a kidney biopsy within 2 years that showed class III, IV, or V (alone or in combination with class III or IV) were eligible. Patients were randomly assigned (1: 1) to oral voclosporin (23.7 mg twice daily) or placebo, on a background of mycophenolate mofetil (1 g twice daily) and rapidly tapered low-dose oral steroids, by use of an interactive web response system. The primary endpoint was complete renal response at 52 weeks defined as a composite of urine protein creatinine ratio of 0.5 mg/mg or less, stable renal function (defined as estimated glomerular filtration rate [eGFR] >= 60 mL/min/1.73 m(2) or no confirmed decrease from baseline in eGFR of >20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or for 7 or more days during weeks 44 through 52, just before the primary endpoint assessment. Safety was also assessed. Efficacy analysis was by intention-to-treat and safety analysis by randomised patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03021499.Findings Between April 13, 2017, and Oct 10, 2019, 179 patients were assigned to the voclosporin group and 178 to the placebo group. The primary endpoint of complete renal response at week 52 was achieved in significantly more patients in the voclosporin group than in the placebo group (73 [41%] of 179 patients vs 40 [23%] of 178 patients; odds ratio 2.65; 95% CI 1.64-4.27; p
- Published
- 2021
24. Low-Dose Corticosteroid Combined With Mycophenolate Mofetil for IgA Nephropathy With Stage 3 or 4 CKD: A Retrospective Cohort Study
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Ming Bai, Feng Ma, Shiren Sun, and Jin Zhao
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medicine.medical_specialty ,medicine.drug_class ,Renal function ,urologic and male genital diseases ,Gastroenterology ,Nephropathy ,Adrenal Cortex Hormones ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Pharmacology (medical) ,Renal Insufficiency, Chronic ,Retrospective Studies ,Pharmacology ,Proteinuria ,business.industry ,Glomerulonephritis, IGA ,Retrospective cohort study ,Mycophenolic Acid ,medicine.disease ,Tolerability ,Corticosteroid ,medicine.symptom ,business ,Immunosuppressive Agents ,Glomerular Filtration Rate ,Kidney disease - Abstract
Purpose This study assessed the long-term (10-year) tolerability and efficacy of a low-dose corticosteroid combined with mycophenolate mofetil (CS + MMF) in the treatment of immunoglobulin A nephropathy (IgAN) with stage 3/4 chronic kidney disease and proteinuria in clinical practice in China. Methods Data from patients with biopsy-proven IgAN, stage 3/4 chronic kidney disease (estimated glomerular filtration rate 15–59 mL/min/1.73 m2), and proteinuria (urinary protein excretion ≥1.0 g/d) and who were treated with uncontrolled supportive care (USC), CS, or CS + MMF between January 2008 and December 2017 were included. The primary end point was the prevalence of the composite outcome of any of the following conditions: a reduction in estimated glomerular filtration rate of ≥50%, end-stage renal disease, and death. Findings Of the 120 enrolled patients, 44, 25, and 51 were treated with USC, CS, and CS + MMF, respectively. The median follow-up time was 40.1 months (IQR, 29.1–67.8 months). The prevalences of the composite outcome were 63.6%, 56.0%, and 19.6%, respectively (P Implications CS + MMF may have more promising efficacy than USC or CS in renal-function preservation in patients with IgAN and chronic kidney disease in the Chinese population. However, attention should be paid to the increased risk for death due to severe pneumonia.
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- 2021
25. Treatment of moderate to severe orbitopathy: Current modalities and perspectives
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Juliette Abeillon, Françoise Borson-Chazot, Philippe Caron, and Nadia Bouzehouane
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Pediatrics ,medicine.medical_specialty ,Receptor complex ,endocrine system diseases ,Exophthalmos ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Disease ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Tocilizumab ,Adrenal Cortex Hormones ,medicine ,Humans ,Modalities ,Radiotherapy ,Teprotumumab ,business.industry ,Thyroid ,Receptors, Thyrotropin ,General Medicine ,Mycophenolic Acid ,Graves Ophthalmopathy ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Rituximab ,medicine.symptom ,business ,medicine.drug - Abstract
Graves' orbitopathy (GO) is the primary cause of exophthalmos in adults. It appears in 30 to 50% of patients with Graves' disease. About 5% are moderate-to-severe cases that might be see-threatening or lead to long term disabling sequelae. Recommendations have been established in 2016 by the European thyroid association (ETA) and the European group on Grave's orbitopathy (EUGOGO), suggesting a wide use of corticosteroids in moderate to severe forms. However, disappointing results have been reported in 20 to 30% of cases. Improved understanding of pathophysiological mechanisms has allowed the use of non-specific immunomodulatory agents, currently under evaluation, and which place in the therapeutic strategy remains to be determined. Very recently, new promising therapeutic advances have emerged with the identification of new therapeutic targets, such as the TSH receptor and IGF-1 receptor complex.
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- 2021
26. Donor Ethnicity and Kidney Transplant Outcomes in African Americans
- Author
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Bhavna Chopra, Khaled Nashar, and Kalathil K Sureshkumar
- Subjects
Adult ,Male ,medicine.medical_specialty ,Tissue and Organ Procurement ,Databases, Factual ,Calcineurin Inhibitors ,Kidney ,Kidney transplant ,Gastroenterology ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Genetic risk ,Proportional Hazards Models ,Transplantation ,business.industry ,Proportional hazards model ,Graft Survival ,Middle Aged ,Mycophenolic Acid ,Kidney Transplantation ,Tissue Donors ,Black or African American ,Calcineurin ,Organ procurement ,Treatment Outcome ,medicine.anatomical_structure ,Kidney Failure, Chronic ,Female ,Surgery ,business ,Donor kidney - Abstract
Background Transplantation of African American (AA) compared to non-AA donor kidneys is generally associated with inferior outcomes. It is unclear whether enhanced genetic risk associated with AA donor kidneys would be counterbalanced by favorable immunologic matching when AA donor kidneys are transplanted into AA recipients. We aimed to compare the outcomes of AA vs non-AA deceased-donor kidneys (DDKs) stratified by kidney donor profile index (KDPI) that were transplanted into AA recipients. Methods Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified AA DDK recipients from 2000 to 2015 who received peri-operative induction followed by calcineurin inhibitor/mycophenolate mofetil maintenance. These patients were divided into 4 KDPI groups (0%-20%, 21%-50%, 51%-85%, and 86%-100%). Adjusted long-term graft and patient outcomes were compared between AA recipients of kidneys from AA vs non-AA donors in each KDPI category using a multivariable Cox model. Results Among a total of 17,516 AA DDK transplant recipients, 3303 were in KDPI 0%-20% (AA donor = 239; non-AA donor = 3064), 5821 in KDPI 21%-50% (AA donor = 1414; non-AA donor = 4407), 6364 in KDPI 51%-85% (AA donor = 1619; non-AA donor = 4745), and 2028 in KDPI 86%-100% (AA donor = 932; non-AA donor = 1096) groups. Adjusted overall graft, death-censored graft, and patient survival were similar between AA recipients of AA vs non-AA donor kidneys across all KDPI groups. Discussion Our study showed similar outcomes for transplanting AA vs non-AA deceased-donor kidneys into AA recipients despite the generally observed inferior outcomes associated with AA donor kidney transplantation.
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- 2021
27. Mycophenolate mofetil for the treatment of cutaneous lichen planus: A retrospective case series
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William W. Huang, Matthew L. Hrin, Steven R. Feldman, and Arjun M. Bashyam
- Subjects
Male ,medicine.medical_specialty ,Drug Tapering ,Drug Substitution ,business.industry ,Lichen Planus ,MEDLINE ,Dermatology ,Middle Aged ,Mycophenolic Acid ,Mycophenolate ,Treatment Outcome ,Recurrence ,medicine ,Drug Evaluation ,Humans ,Drug Therapy, Combination ,Female ,business ,Immunosuppressive Agents ,Aged ,Retrospective Studies ,Steroids, Fluorinated - Published
- 2021
28. A 65-year-old Woman With Persistent Dyspnea, Arthritis, and Raynaud's Phenomenon
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Scott Beegle, Biplab K. Saha, and Woon H. Chong
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medicine.medical_specialty ,Arthritis ,Antisynthetase syndrome ,030204 cardiovascular system & hematology ,Polymyositis ,Pulmonary function testing ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Myositis ,business.industry ,Interstitial lung disease ,Raynaud Disease ,General Medicine ,Mycophenolic Acid ,respiratory system ,Dermatomyositis ,medicine.disease ,Dermatology ,respiratory tract diseases ,Dyspnea ,Antirheumatic Agents ,Drug Therapy, Combination ,Female ,Lung Diseases, Interstitial ,Rituximab ,business ,Cryptogenic Organizing Pneumonia ,Rare disease - Abstract
Antisynthetase syndrome (AS) is a rare disease that affects patients with inflammatory myopathies such as polymyositis (PM) and dermatomyositis (DM). In patients with AS, up to 95% of patients develop antisynthetase syndrome-associated interstitial lung disease (AS-ILD). Although AS-ILD commonly occurs in patients with a well-established diagnosis of AS, it can be the first or only manifestation of an occult AS. The frequency of interstitial lung disease (ILD), myopathy, and skin involvement are often dependent on the type of myositis-specific antibodies present. AS-ILD patients who are positive for both anti-Jo-1 and anti-SSA/RO-52 autoantibodies often present with a severe degree of lung restriction on pulmonary function tests and radiologic imaging with an inadequate response toward immunosuppressive therapies. We describe a 65-year-old woman who presents with chronic dyspnea. She was initially diagnosed with corticosteroid-resistant cryptogenic organizing pneumonia based on the radiological findings on her CT chest. Her symptoms did not improve, and she suffered from intolerable corticosteroid-related side effects. Reviews of systems were positive for arthritis and Raynaud's phenomenon. She was found to have elevated inflammatory markers and autoantibodies such as anti-Jo-1, anti-RO-52, and anti-SSA. A diagnosis of AS-ILD resistant to corticosteroid therapy was made. Her lung function improved with combination therapy of mycophenolate and rituximab. Our case highlights that a detailed history and physical exam, compatible radiologic imaging, and autoantibodies are essential for the diagnosis of AS-ILD.
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- 2021
29. Investigating a Modified Apparatus to Discriminate the Dissolution Capacity In Vitro and Establish an IVIVC of Mycophenolate Mofetil Tablets in the Fed State
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Guoqing Zhang, Ming Sun, Shan Jiang, Lei Wang, Yuexiang Tan, and Zeneng Cheng
- Subjects
Chromatography ,Chemistry ,Cmax ,Administration, Oral ,Pharmaceutical Science ,02 engineering and technology ,Absorption (skin) ,Mycophenolic Acid ,Bioequivalence ,021001 nanoscience & nanotechnology ,Mycophenolate ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,IVIVC ,Solubility ,Therapeutic Equivalency ,Humans ,Dissolution testing ,0210 nano-technology ,Dissolution ,Tablets - Abstract
In this study, a modified dissolution apparatus was developed by equipping a USP apparatus Ⅰ with an open-loop system to discriminate the dissolution capacity in vitro and establish an in vitro and in vivo correlation (IVIVC) for mycophenolate mofetil (MMF) tablets. MMF had strong pH-dependent solubility that could influence the dissolution rate in vivo after the meal. Dissolution tests involving reference (Cellcept®) and test formulations (F1 and F2) were conducted using pH 4.5 acetate buffer to simulate gastric fluids in the fed state. The dissolution profiles of the reference and test formulations were distinguished by using the modified dissolution apparatus and compared with those determined using the USP apparatuses Ⅱ and Ⅳ, and the dissolution capacities of the formulations were discriminated at different sampling time-points. The results of human bioequivalence (BE) studies in the fed state were consistent with in vitro evaluations that the maximum concentrations (Cmax, in vivo) of both F1 and F2 fell below the acceptable range (80.00%). A level A IVIVC between the absorption fraction in vivo and dissolution in vitro, and a level C correlation between Cmax, in vivo and Cmax, in vitro, were established to guide the optimization of the tablet formulation containing MMF.
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- 2021
30. Delayed Calcineurin Inhibitor Introduction Without Antibody Induction in Liver Transplantation Is Safe and Helps Preserve Kidney Function
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P. Kositamongkol, Chutwichai Tovikkai, Charnwit Assawasirisin, Pholasith Sangserestid, Wethit Dumronggittigule, S. Limsrichamrern, Prawej Mahawithitwong, and Yongyut Sirivatanauksorn
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Calcineurin Inhibitors ,Urology ,Renal function ,Patient characteristics ,Liver transplantation ,Tacrolimus ,Antibody induction ,Humans ,Medicine ,Retrospective Studies ,Immunosuppression Therapy ,Transplantation ,business.industry ,Acute kidney injury ,Acute Kidney Injury ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Liver Transplantation ,Calcineurin ,Case-Control Studies ,Female ,Surgery ,business ,Immunosuppressive Agents ,Serum creatinine level - Abstract
Introduction Acute kidney injury (AKI) is common after liver transplantation and affects outcome after liver transplantation. Antibody induction is commonly used to reduce dose and/or to delay introduction of calcineurin inhibitor (CNI) but is very expensive. We propose a modified immunosuppressive protocol that delays administration of CNI for 48 to 72 hours without antibody induction. This study evaluates the results of our new protocol. Material and Methods A retrospective case-control study was performed. Study patients had induction with steroid and mycophenolate mofetil without antibody induction, and CNI administration was delayed for 48 to 72 hours. Control patients received CNI and steroid induction without antibody induction, and CNI was continued posttransplant. AKI was defined as an increase in serum creatinine level of at least 1.5 times the pretransplant baseline within the first postoperative week. Results Sixty liver transplant recipients from 2013 to 2015 were included in this study (30 in the delayed CNI group and 30 in the control group). The patient characteristics and intraoperative factors were comparable in both groups. AKI developed in 11 patients in the study group and in 20 patients in the control group (37% vs 66.7%; P = .02). There was no acute rejection observed in the first month in either group. Conclusion We have demonstrated that delayed CNI introduction without antibody induction is safe and helps preserve kidney function. Antibody induction can be omitted safely in a delayed CNI introduction protocol to reduce the cost of liver transplantation without increasing the risk of acute rejection.
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- 2021
31. Induction and maintenance therapy of lupus nephritis: an obituary
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Brad H. Rovin, Hans-Joachim Anders, and Yutian Lei
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Proteinuria ,business.industry ,Lupus nephritis ,Inflammation ,Mycophenolic Acid ,Obituary ,medicine.disease ,Lupus Nephritis ,Treatment Outcome ,Maintenance therapy ,Nephrology ,Immunology ,medicine ,Humans ,medicine.symptom ,business ,Immunosuppressive Agents - Published
- 2021
32. 56-Year-Old Man With Profuse Diarrhea
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Fernando F. Stancampiano and Joshua Kwon
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Diarrhea ,Male ,Pediatrics ,medicine.medical_specialty ,Protein-Losing Enteropathies ,MEDLINE ,Cryptosporidiosis ,Colonoscopy ,Diagnosis, Differential ,Feces ,Immunocompromised Host ,medicine ,Humans ,Kidney transplantation ,Travel ,medicine.diagnostic_test ,business.industry ,General Medicine ,Middle Aged ,Mycophenolic Acid ,Nitro Compounds ,medicine.disease ,Kidney Transplantation ,Thiazoles ,alpha 1-Antitrypsin ,medicine.symptom ,business ,Hypoalbuminemia - Published
- 2021
33. Three-year outcomes from the CRADLE study in de novo pediatric kidney transplant recipients receiving everolimus with reduced tacrolimus and early steroid withdrawal
- Author
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Stephen D. Marks, Patricia Lopez, Martin Christian, Matthias Meier, Burkhard Tönshoff, Udaykiran Veldandi, Marc Cousin, Anna Bjerre, Lars Pape, Priti Pandey, Luca Dello Strologo, Helio Tedesco-Silva, and Robert Ettenger
- Subjects
Graft Rejection ,medicine.medical_specialty ,Basiliximab ,Urology ,Renal function ,Tacrolimus ,End stage renal disease ,Drug withdrawal ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Everolimus ,Child ,Kidney transplantation ,Transplantation ,business.industry ,Graft Survival ,Mycophenolic Acid ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Discontinuation ,Steroids ,business ,Immunosuppressive Agents ,Glomerular Filtration Rate ,medicine.drug - Abstract
CRADLE was a 36-month multicenter study in pediatric (≥1 to
- Published
- 2021
34. Laboratory monitoring requirements during mycophenolate mofetil therapy for dermatologic conditions: A single-institution retrospective chart review
- Author
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Reid A. Waldman and Bruce Strober
- Subjects
medicine.medical_specialty ,Leukopenia ,business.industry ,Laboratory monitoring ,MEDLINE ,Dermatology ,Mycophenolic Acid ,Neutropenia ,medicine.disease ,Mycophenolate ,Chart review ,medicine ,Humans ,Prednisone ,Drug Therapy, Combination ,Single institution ,medicine.symptom ,Laboratories ,Intensive care medicine ,business ,Immunosuppressive Agents ,Retrospective Studies - Published
- 2021
35. Reduced Recurrence of Primary IgA Nephropathy in Kidney Transplant Recipients Receiving Everolimus With Corticosteroid: A Retrospective, Single-Center Study of 135 Transplant Patients
- Author
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Keizo Kaku, Akihiro Tsuchimoto, Yasuhiro Okabe, Hiroshi Noguchi, Kenji Ueki, and Masafumi Nakamura
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.drug_class ,Urology ,Disease ,Single Center ,Tacrolimus ,Nephropathy ,Adrenal Cortex Hormones ,Recurrence ,Interquartile range ,Secondary Prevention ,medicine ,Humans ,Everolimus ,Aged ,Retrospective Studies ,Transplantation ,Kidney ,business.industry ,Graft Survival ,Glomerulonephritis, IGA ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Kidney Transplantation ,medicine.anatomical_structure ,Corticosteroid ,Female ,Surgery ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Long-term kidney allograft survival remains a major clinical challenge. Recurrent glomerulonephritis disease, including recurrence of IgA nephropathy (IgAN), is a significant barrier to long-term kidney allograft survival. We performed a retrospective, observational study to evaluate the role of everolimus (EVR) in the risk of recurrent IgAN.The study included data from 135 patients aged ≥16 years with biopsy-proven IgAN on native kidneys who underwent a kidney transplant (KT) between December 2002 and December 2018.Patients who underwent de novo KT received mycophenolate mofetil (MMF) (n = 107) or EVR (n = 28). The mean recipient age in the MMF and EVR groups was 44.9 ± 13.7 and 41.1 ± 10.1, respectively. The median (interquartile range) follow-up period was 90.9 (64.9-115.3) and 21.2 (11.4-30.6) months, respectively (.0001). All patients received continuous corticosteroid and tacrolimus therapy. The death-censored graft survival rate after KT and the recurrence-free survival rate did not differ significantly between the groups. Univariate and multivariate Cox regression analyses identified EVR for de novo KT as an independent predictive factor for recurrence-free survival (P = .024).Our findings suggest that EVR-based regimens with tacrolimus and corticosteroid therapy for de novo KT reduce the recurrence of IgAN compared with MMF-based regimens with tacrolimus and corticosteroid therapy.
- Published
- 2020
36. Distinct peripheral blood molecular signature emerges with successful tacrolimus withdrawal in kidney transplant recipients
- Author
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Miguel Fribourg, German Nudelman, Zhengzi Yi, Sophie Brouard, Lisa Anderson, Paolo Cravedi, Peter S. Heeger, Weijia Zhang, Elena Zaslavsky, and Susan Hartzell
- Subjects
Graft Rejection ,Regulatory T cell ,medicine.medical_treatment ,chemical and pharmacologic phenomena ,030230 surgery ,Peripheral blood mononuclear cell ,Tacrolimus ,Article ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Prednisone ,Immunity ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Kidney transplantation ,Transplantation ,business.industry ,Immunosuppression ,Mycophenolic Acid ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,medicine.anatomical_structure ,Immunology ,Leukocytes, Mononuclear ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Tacrolimus (Tac) is an effective anti-rejection agent in kidney transplantation, but its off-target effects make withdrawal desirable. Although studies indicate that Tac can be safely withdrawn in a subset of kidney transplant recipients, immune mechanisms that underlie successful vs unsuccessful Tac removal are unknown. We performed microarray analyses of peripheral blood mononuclear cells (PBMC) RNA from subjects enrolled in the Clinical Trials in Organ Transplantation-09 study in which we randomized stable kidney transplant recipients to Tac withdrawal or maintenance of standard immunosuppression beginning 6 months after transplant. Eight of 14 subjects attempted but failed withdrawal, while six developed stable graft function for ≥2 years on mycophenolate mofetil plus prednisone. Whereas failed withdrawal upregulated immune activation genes, successful Tac withdrawal was associated with a downregulatory and proapoptotic gene program enriched within T cells. Functional analyses suggested stronger donor-reactive immunity in subjects who failed withdrawal without evidence of regulatory T cell dysfunction. Together, our data from a small, but unique, patient cohort support the conclusion that successful Tac withdrawal is not simply due to absence of donor-reactive immunity but rather is associated with an active immunological process.
- Published
- 2020
37. A New Standard in Graft-versus-Host Disease Prophylaxis? An Introduction to Blood and Marrow Transplant Clinical Trials Network 1703
- Author
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Bryce Waldman, Linda J. Burns, Daniel J. Weisdorf, Zachariah DeFilipp, Aaron L. Leppin, William A. Wood, Nandita Khera, Steven Z. Pavletic, and Samantha Jaglowski
- Subjects
Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Cyclophosphamide ,Graft vs Host Disease ,chemical and pharmacologic phenomena ,Disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,Bone Marrow ,immune system diseases ,Multicenter trial ,Internal medicine ,medicine ,Humans ,Multicenter Studies as Topic ,Randomized Controlled Trials as Topic ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Mycophenolic Acid ,medicine.disease ,Tacrolimus ,Clinical trial ,surgical procedures, operative ,Graft-versus-host disease ,030220 oncology & carcinogenesis ,Methotrexate ,Unrelated Donors ,business ,030215 immunology ,medicine.drug - Abstract
Effective immunosuppressive regimens to prevent the development of graft-versus-host disease (GVHD) are essential to the success of allogeneic hematopoietic cell transplantation (HCT). After revolutionizing haploidentical transplantation, post-transplantation cyclophosphamide (PTCy) is now being evaluated for HCT performed from related and unrelated donors. In this setting, two recent randomized studies have demonstrated lower rates of GVHD and superior GVHD-free, relapse-free survival with PTCy as compared to conventional GVHD prophylaxis. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is currently conducting a large, randomized phase III, multicenter trial (BMT CTN 1703) comparing PTCy/tacrolimus/mycophenolate mofetil to tacrolimus/methotrexate as GVHD prophylaxis regimens in reduced-intensity allogeneic HCT. In this introductory manuscript, we review the ongoing study, highlight its importance to field, and explore the possible implications of results on clinical practice.
- Published
- 2020
38. Evidence-based best practice advice for patients treated with systemic immunosuppressants in relation to COVID-19
- Author
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Alexander Herbst, Robert S. Kirsner, Michael Abrouk, Yumeng Li, Jeffrey D. McBride, Megan Cronin, Fabrizio Galimberti, and Joshua D. Fox
- Subjects
medicine.medical_specialty ,Evidence-based practice ,Azathioprine ,Dermatology ,Severe Acute Respiratory Syndrome ,Skin Diseases ,Article ,Mycophenolic acid ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Prednisone ,medicine ,Humans ,Janus Kinase Inhibitors ,Intensive care medicine ,030203 arthritis & rheumatology ,Biological Products ,Evidence-Based Medicine ,SARS-CoV-2 ,business.industry ,COVID-19 ,Evidence-based medicine ,Mycophenolic Acid ,Discontinuation ,Methotrexate ,Cyclosporine ,Rituximab ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
The emergence of the COVID-19 pandemic has led to significant uncertainty among physicians and patients about the safety of immunosuppressive medications used for the management of dermatologic conditions. We review available data on commonly used immunosuppressants and their effect on viral infections beyond COVID-19. Notably, the effect of some immunosuppressants on viruses related to SARS-CoV2, including SARS and MERS, has been previously investigated. In the absence of data on the effect of immunosuppressants on COVID-19, these data could be used to make clinical decisions on initiation and continuation of immunosuppressive medications during this pandemic. In summary, we recommend considering the discontinuation of oral Janus kinase (JAK) inhibitors and prednisone; considering the delay of rituximab infusion; and suggesting the careful continuation of cyclosporine, mycophenolate, azathioprine, methotrexate, and biologics in patients currently benefitting from such treatments.
- Published
- 2020
39. Therapeutic Strategies for Treatment of Immune-Mediated Hemolytic Anemia
- Author
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Robert Goggs
- Subjects
Hemolytic anemia ,Blood transfusion ,medicine.medical_treatment ,Azathioprine ,Mycophenolate ,Proinflammatory cytokine ,Dogs ,Antithrombotic ,medicine ,Animals ,Dog Diseases ,Enzyme Inhibitors ,Small Animals ,Plasma Exchange ,medicine.diagnostic_test ,business.industry ,Immunosuppression ,Mycophenolic Acid ,medicine.disease ,Therapeutic drug monitoring ,Immunology ,Cyclosporine ,Anemia, Hemolytic, Autoimmune ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Immune-mediated hemolytic anemia is a common hematologic disorder in dogs. Disease management involves immunosuppression using glucocorticoids, potentially in combination with other medications such as azathioprine, cyclosporine, or mycophenolate mofetil. Therapeutic drug monitoring may enhance the utility and maximize the safety of cyclosporine and mycophenolate mofetil. The disease is proinflammatory and prothrombotic. Antithrombotic drug administration is therefore essential, and anticoagulant therapy should be initiated at the time of diagnosis. Additional therapies include red blood cell transfusion to support blood oxygen content. Future therapies may include therapeutic plasma exchange, anti-CD20 monoclonal antibodies, and complement inhibitors.
- Published
- 2020
40. Liver transplant immunosuppression during the COVID-19 pandemic
- Author
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Miquel Navasa and Xavier Forns
- Subjects
0301 basic medicine ,Trasplante hepático ,medicine.medical_treatment ,Review ,Liver transplantation ,Adaptive Immunity ,chemistry.chemical_compound ,0302 clinical medicine ,Postoperative Complications ,Citoquinas ,Inmunomoduladores ,Drug Interactions ,Liver transplant ,education.field_of_study ,Leukopenia ,TOR Serine-Threonine Kinases ,Gastroenterology ,Immunosuppression ,Hepatitis C ,Cytokines ,030211 gastroenterology & hepatology ,Disease Susceptibility ,medicine.symptom ,Coronavirus Infections ,Immunosuppressive Agents ,medicine.drug ,medicine.medical_specialty ,Population ,Calcineurin Inhibitors ,Pneumonia, Viral ,Antiviral Agents ,Article ,Inmunosupresión ,Immunomodulation ,03 medical and health sciences ,Betacoronavirus ,Immunocompromised Host ,Tocilizumab ,Neumonía ,medicine ,Humans ,Everolimus ,Intensive care medicine ,education ,Glucocorticoids ,Pandemics ,Immunosuppression Therapy ,Sirolimus ,Hepatology ,business.industry ,SARS-CoV-2 ,Contraindications, Drug ,COVID-19 ,Pneumonia ,Mycophenolic Acid ,medicine.disease ,Tacrolimus ,Immunity, Innate ,Liver Transplantation ,COVID-19 Drug Treatment ,030104 developmental biology ,chemistry ,Ritonavir ,business - Abstract
Resumen La infección por el virus SARS-CoV-2 ha producido una pandemia con graves consecuencias sobre nuestro sistema sanitario. Aunque el colectivo de pacientes trasplantados hepáticos representa solo una minoría de la población, los hepatólogos que seguimos a estos pacientes hemos intentado coordinar esfuerzos para protocolizar el manejo de la inmunosupresión durante la infección por SARS-CoV-2. Aunque no hay estudios sólidos que avalen recomendaciones generales, las experiencias con otras infecciones víricas (hepatitis C, citomegalovirus) sugieren que el manejo de la inmunosupresión sin micofenolato mofetilo ni inhibidores m-Tor (fármacos que además se asocian a leucopenia y linfopenia) puede resultar beneficiosa. Es importante además prestar atención a las posibles interacciones farmacológicas, especialmente en el caso de tacrolimus, con algunos de los tratamientos con efecto antiviral que se administran en el contexto de la covid-19 (lopinavir/ritonavir, azitromicina). Finalmente, deberá tenerse en cuenta el efecto inmunosupresor de fármacos inmunomoduladores (tocilizumab y similares) que se administran en pacientes con enfermedad pulmonar severa. En el artículo se revisan los mecanismos de actuación de los diferentes fármacos inmunosupresores, su potencial efecto sobre la infección por SARS-CoV-2 y se sugieren unas pautas en el manejo de la inmunosupresión.
- Published
- 2020
41. Rituximab as a rescue treatment added on mycophenolate mofetil background therapy in progressive systemic sclerosis associated interstitial lung disease unresponsive to conventional immunosuppression
- Author
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Judit LLuch, Javier Narváez, Joan M. Nolla, Maria Molina-Molina, Patricio Luburich, Vanesa Vicens-Zygmunt, and Marcos Anibal Yañez
- Subjects
medicine.medical_specialty ,Cyclophosphamide ,medicine.medical_treatment ,Gastroenterology ,Pulmonary function testing ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Prednisone ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Adverse effect ,Immunosuppression Therapy ,030203 arthritis & rheumatology ,business.industry ,Interstitial lung disease ,Immunosuppression ,Retrospective cohort study ,Mycophenolic Acid ,medicine.disease ,Observational Studies as Topic ,Treatment Outcome ,Anesthesiology and Pain Medicine ,Scleroderma, Diffuse ,Rituximab ,Lung Diseases, Interstitial ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Objective To test whether the use of rituximab (RTX) is effective and safe as a rescue therapy add-on treatment to mycophenolate (MMF) in patients with progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) in whom conventional immunosuppressants (IS) have failed. Methods Longitudinal retrospective observational study of a cohort of patients with SSc-ILD that started treatment with RTX due to ongoing lung function impairment despite treatment with glucocorticoids and IS (cyclophosphamide and/or MMF). All patients were treated with 2 or more cycles of RTX and evaluated for at least 12 months. Results Twenty-four patients were included. Before initiation of RTX the mean decline in%pFVC and %pDLCO during the previous 2 years (delta) was −12.9% and −12.5%, respectively. After 1 year of treatment with RTX, a significant improvement in %pFVC (∆+8.8% compared to baseline, 95% CI: −13.7 to −3.9; p = 0.001) and%pDLCO (∆+4.6%, 95% CI: −8.2 to −0.8; p = 0.018) was observed. In addition, there was a significant reduction in the median dose of prednisone and it could be suspended in 25% of patients. At 2 years of treatment, RTX had been discontinued in 9 patients (due to adverse events in 3 cases and inefficacy in 6). In the 15 patients (62.5%) that completed 24 months of therapy, the statistically significant amelioration in pulmonary function test parameters was maintained: ∆%pFVC: +11.1% (95% CI: −17.6 to −4.5; p = 0.003) and ∆%pDLCO: +8.7% (95% CI: −13.9 to −8.3; p = 0.003). Conclusion Based on our results, RTX's use as an add-on treatment to MMF appears to be effective as a rescue therapy in patients with a more aggressive SSc-ILD phenotype.
- Published
- 2020
42. Beyond 10 years, with or without an intestinal graft: Present and future?
- Author
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Olivier Corcos, Christophe Chardot, Sophie Courbage, Louise Galmiche, Florence Lacaille, Cécile Lambe, Olivier Goulet, Marion Rabant, Danielle Canioni, Francisca Joly, and Cécile Talbotec
- Subjects
Graft Rejection ,medicine.medical_specialty ,medicine.medical_treatment ,030230 surgery ,Liver transplantation ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Child ,Sirolimus ,Transplantation ,business.industry ,Graft Survival ,Mycophenolic Acid ,Micronutrient ,Fat malabsorption ,Regimen ,surgical procedures, operative ,Parenteral nutrition ,Complication ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Long-term outcomes in children undergoing intestinal transplantation remain unclear. Seventy-one children underwent intestinal transplantation in our center from 1989 to 2007. We report on 10-year posttransplant outcomes with (group 1, n = 26) and without (group 2, n = 9) a functional graft. Ten-year patient and graft survival rates were 53% and 36%, respectively. Most patients were studying or working, one third having psychiatric disorders. All patients in group 1 were weaned off parenteral nutrition with mostly normal physical growth and subnormal energy absorption. Graft histology from 15 late biopsies showed minimal abnormality. However, micronutrient deficiencies and fat malabsorption were frequent; biliary complications occurred in 4 patients among the 17 who underwent liver transplantation; median renal clearance was 87 mL/min/1.73 m2 . Four patients in group 1 experienced late acute rejection. Among the 9 patients in group 2, 4 died after 10 years and 2 developed significant liver fibrosis. Liver transplantation and the use of a 3-drug regimen including sirolimus or mycophenolate mofetil were associated with improved graft survival. Therefore, intestinal transplantation may enable a satisfactory digestive function in the long term. The prognosis of graft removal without retransplantation is better than expected. Regular monitoring of micronutrients, early psychological assessment, and use of sirolimus are recommended.
- Published
- 2020
43. Comparative Study of Mizoribine and Mycophenolate Mofetil Combined with a Calcineurin Inhibitor-Based Immunosuppressive Regimen in Patients with Alternative Donor Hematopoietic Cell Transplantation
- Author
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Erlie Jiang, Yi He, Donglin Yang, Aiming Pang, R L Zhang, Sizhou Feng, Weihua Zhai, Mingzhe Han, Jialin Wei, Yong Huang, Qiaoling Ma, and Li Zhang
- Subjects
medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Calcineurin Inhibitors ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,Internal medicine ,medicine ,Humans ,Transplantation ,Mizoribine ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Immunosuppression ,Hematology ,Mycophenolic Acid ,Calcineurin ,Cohort ,Ribonucleosides ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Cytomegalovirus (CMV) infection and graft-versus-host disease (GVHD) remain the major causes of nonrelapse mortality (NRM) in patients following alternative donor hematopoietic stem cell transplantation (HCT). Mizoribine (MZR) showed an anti-CMV effect in addition to its immunosuppressive effect in patients with renal transplantation. In this study, we aimed to evaluate the efficacy and safety of MZR combined with a calcineurin inhibitor (CNI) as a method of prophylactic immunosuppression in recipients following alternative donor HCT. Eighty patients were enrolled in the study and randomized to the MZR (n = 40) or MMF (n = 40) cohort before transplantation conditioning. Analyses involved a comparison of the outcomes between the 2 cohorts, as well as risk analyses of early nonrelapse mortality (NRM) and severe CMV infection. In contrast to MMF, MZR was associated with a lower but statistically nonsignificant median CMV DNA peak load (P = .075), significantly fewer episodes of persistent/refractory infection (odds ratio [OR], .12), and a lower failure rate of CMV treatment (OR, .82), but a significantly higher rate of hyperuricemia (OR, 2.75). Transplantation efficacy was comparable in the 2 cohorts regarding engraftment, the development of secondary poor graft function and GVHD, and the estimated OS and PFS. The 1-year NRM of the MZR cohort did not differ from that of the MMF cohort, whereas the rate of 1-year NRM caused by viral infections was reduced in the MZR cohort and was of borderline statistical significance (P = .05). In the multivariate analysis, lower doses of CD34+ cells in grafts (hazard ratio [HR], 3.65) and persistent/refractory CMV infections (versus no CMV infection: HR, 7.31; versus CMV infection that was not persistent/refractory: HR, 4.46) were predictors of increased 1-year NRM. The use of MMF (versus MZR cohort: OR, 11.54) and grade II-IV acute GVHD (OR, 15.32) were independent risk factors for developing persistent/refractory CMV infection. When combined with CNIs, MZR functioned well in terms of both immunosuppression and reduced severity of CMV infection; however, further studies are warranted to verify its use as a potential immunosuppressant for alternative donor HCT.
- Published
- 2020
44. Effect of mycophenolic acid on inosine monophosphate dehydrogenase (IMPDH) activity in liver transplant patients
- Author
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Wolfgang Stremmel, N. Metzendorf, Karl-Heinz Weiss, S. Böhnisch, A. Mehrabi, Christian Rupp, Martin Zeier, Claudia Sommerer, M. Neuberger, and Daniel Gotthardt
- Subjects
Male ,Inosine monophosphate ,medicine.medical_specialty ,medicine.medical_treatment ,Liver transplantation ,Mycophenolate ,Gastroenterology ,Mycophenolic acid ,Cohort Studies ,03 medical and health sciences ,IMP Dehydrogenase ,Postoperative Complications ,0302 clinical medicine ,IMP dehydrogenase ,Internal medicine ,medicine ,Humans ,Enzyme Inhibitors ,Aged ,Hepatology ,business.industry ,Area under the curve ,Immunosuppression ,Middle Aged ,Mycophenolic Acid ,Liver Transplantation ,030220 oncology & carcinogenesis ,Toxicity ,Female ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Summary Background Due to the development of immunosuppressants, the focus in transplanted patients has shifted from short-term to long-term survival as well as a better adjustment of these drugs in order to prevent over- and under-immunosuppression. Mycophenolic acid (MPA) is a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) and approved for prophylaxis of acute rejection after kidney, heart, and liver transplantation, where it has become a part of the standard therapy. Targeting inosine monophosphate IMPDH activity as a surrogate pharmacodynamic marker of MPA-induced immunosuppression may allow a more accurate assessment of efficacy and aid in limiting toxicity in liver transplanted patients. Aim Assess IMPDH-inhibition in liver transplant recipients and its impact on biliary/infectious complications, acute cellular rejection (ACR) and liver dependent survival. Methods This observational cohort study comprises 117 liver transplanted patients that were treated with mycophenolate mofetil (MMF) for at least 3 months. Blood samples (BS) were collected and MPA serum level and IMPDH activity were measured before (t(0)), 30 minutes (t(30)) and 2 h after (t(120)) MMF morning dose administration. Regarding MPA, we assessed the area under the curve (AUC). Patients were prospectively followed up for one year and assessed for infectious and biliary complications, episodes of ACR and liver dependent survival. Results The MPA levels showed a broad interindividual variability at t(0) (2.0 ± 1.8 ng/ml), t(30) (12.7 ± 9.0 ng/ml) and t(120) (7.5 ± 4.3 ng/ml). Corresponding IMPDH activity was at t(o) (23.2 ± 9.5 nmol/h/mg), at t(30) (16.3 ± 8.8 nmol/h/mg) and t(120) (18.2 ± 8.7 nmol/h/mg). With regard to MPA level we found no correlation with infectious or biliary complications within the follow-up period. Patients with baseline IMPDH(a) below the median had significant more viral infections (6 (10.2%) vs. 17 (29.3%); P = 0.009) with especially more cytomegalovirus (CMV) infections (1 (3.4%) vs. 6 (21.4%); P = 0.03)). Furthermore, patients with baseline IMPDH(a) above the median developed more often non-anastomotic biliary strictures (8 (13.6%) vs. 1 (1.7%), P = 0.03). We found the group reaching the combined clinical endpoint of death and re-transplantation showing significantly lower MPA baseline values (t(0) 0.9 ± 0.7 vs. 2.1 ± 1.8 μg/ml Mann-Whitney-U: P = 0.02). We calculated a simplified MPA(AUC) with the MPA level at baseline, 30 and 120 minutes after MPA administration. Whereas we found no differences with regard to baseline characteristics at entry into the study patients with MPA (AUC) below the median experienced significantly more often the combined clinical endpoint (12.1% (7/58) vs. 0.0% (0/57); P = 0.002) and had a reduced actuarial re-transplantation-free survival (1.0 year vs. 0.58 years; Log-rank: P = 0.007) during the prospective one-year follow-up period. In univariate and multivariate analysis including gender, age, BMI, ACR, MPA (AUC) and IMPDH(a) only BMI, MPA (AUC) and IMPDH(a) were independently associated with reduced actuarial re-transplantation-free survival. Conclusion MPA-levels and IMPDH-activity in liver transplanted patients allows individual risk assessment. Patients with higher IMPDH inhibition acquire more often viral infections. Insufficient IMPDH inhibition is associated with development of non-anastomotic bile duct strictures and reduced re-transplantation-free survival.
- Published
- 2020
45. Efficacy and safety of basiliximab as initial immunosuppression in liver transplantation: A single center study
- Author
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Amr Ragab, Imam Waked, Mohamed Hashim, Ayman Alsebaey, and Hossam Eldeen Soliman
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Time Factors ,Basiliximab ,medicine.medical_treatment ,Urology ,Specialties of internal medicine ,Liver transplantation ,Single Center ,Rejection ,Tacrolimus ,03 medical and health sciences ,0302 clinical medicine ,Calcineurin inhibitors ,Humans ,Medicine ,Transplantation ,Hepatology ,business.industry ,Graft Survival ,Immunosuppression ,General Medicine ,Middle Aged ,Mycophenolic Acid ,Liver Transplantation ,Calcineurin ,Regimen ,Treatment Outcome ,RC581-951 ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,Egypt ,Female ,Steroids ,interleukin-2 ,030211 gastroenterology & hepatology ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Introduction and aim The interleukin-2 receptor antagonist; basiliximab is used to allow delayed introduction of Calcineurin inhibitors (CNI) after liver transplantation and thus delay their renal insult. However, there is only little evidence for the safety and the efficacy of this regimen. This study aimed to evaluate the effectiveness and safety of basiliximab induction in liver transplantation. Materials and methods This study included 89 patients who were classified into two groups: standard triple immunosuppression (IS) regimen of steroid, tacrolimus (TAC) and mycophenolate mofetil (MMF) (n = 47) and induction IS regimen of basiliximab, low dose steroids and MMF with delayed introduction of CNI (n = 42). All patients were followed after liver transplantation for at least six months or until death. Results There were no significant differences in patient survival, graft dysfunction, infection rate or type, or wound healing between both groups. The acute rejection rate was equivalent in both groups. Renal dysfunction in the first six months post-transplant was less in the basiliximab group in comparison to the other group (7.1% and 19.1% respectively). Conclusion Basiliximab-induced IS protocol is a safe regimen that reduces medium-term renal dysfunction and achieves similar survival without increasing the acute rejection or infection rate in liver transplantation recipients.
- Published
- 2020
46. Update on Lupus Nephritis: Core Curriculum 2020
- Author
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Brad H. Rovin, Salem Almaani, Samir V. Parikh, and Sergey V. Brodsky
- Subjects
Male ,Nephrology ,medicine.medical_specialty ,Cyclophosphamide ,Biopsy ,030232 urology & nephrology ,Lupus nephritis ,Autoimmunity ,Adaptive Immunity ,Urinalysis ,Maintenance Chemotherapy ,03 medical and health sciences ,Age Distribution ,0302 clinical medicine ,Maintenance therapy ,Adrenal Cortex Hormones ,Pregnancy ,Renal Dialysis ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,030212 general & internal medicine ,Risk factor ,Intensive care medicine ,Autoantibodies ,Systemic lupus erythematosus ,business.industry ,Induction Chemotherapy ,Mycophenolic Acid ,medicine.disease ,Kidney Transplantation ,Lupus Nephritis ,Immunity, Innate ,Pregnancy Complications ,Transplantation ,Kidney Failure, Chronic ,Female ,Rituximab ,business ,Immunosuppressive Agents ,Hydroxychloroquine ,medicine.drug - Abstract
Systemic lupus erythematosus is a multisystem autoimmune disease that commonly affects the kidneys. Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus and a major risk factor for morbidity and mortality. The pathophysiology of LN is heterogeneous. Genetic and environmental factors likely contribute to this heterogeneity. Despite improved understanding of the pathogenesis of LN, treatment advances have been few and risk for kidney failure remains unacceptably high. This installment in the Core Curriculum of Nephrology provides an up-to-date review of the current understanding of LN epidemiology, pathogenesis, diagnosis, and treatment. Challenging issues such as the management of LN in pregnancy, timing of transplantation, and the evolving role of corticosteroid use in the management of LN are discussed. We review the currently accepted approach to care for patients with LN and highlight deficiencies that need to be addressed to better preserve long-term kidney health and improve outcomes in LN.
- Published
- 2020
47. Mycophenolate mofetil for induction and maintenance of remission in naïve patients with granulomatosis with polyangiitis without renal involvement
- Author
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Yasser Ragab, Yasser Emad, Johannes J. Rasker, and Psychology, Health & Technology
- Subjects
Adult ,Male ,C-ANCA ,medicine.medical_specialty ,030232 urology & nephrology ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,Newly diagnosed ,Mycophenolate ,Gastroenterology ,Maintenance Chemotherapy ,Therapy naive ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,immune system diseases ,Internal medicine ,Eosinophilic ,medicine ,Humans ,cardiovascular diseases ,skin and connective tissue diseases ,Anti-neutrophil cytoplasmic antibody ,030203 arthritis & rheumatology ,business.industry ,Remission Induction ,Granulomatosis with Polyangiitis ,General Medicine ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,n/a OA procedure ,respiratory tract diseases ,Female ,Kidney Diseases ,Granulomatosis with polyangiitis ,business ,Microscopic polyangiitis - Abstract
Antineutrophil cytoplasmic antibodies (ANCA) associated vasculitides include granulomatosis with polyangiitis (GPA, previously called Wegener's), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss). In this report we used mycophenolate mofetil (MMF) and steroids to induce and maintain remission in two newly diagnosed cases with c-ANCA associated GPA. The two patients' maintained remission with no disease relapses during one year follow-up.Copyright © 2018 Sociedad Espanola de Reumatologia y Colegio Mexicano de Reumatologia. Publicado por Elsevier Espana, S.L.U. All rights reserved.
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- 2020
48. Long-Term Effects of the Replacement of Calcineurin Inhibitors With Everolimus and Mycophenolate in Patients With Calcineurin Inhibitor–Related Nephrotoxicity
- Author
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Catherine Klersy, Stefania Guida, Alessandra Greco, Barbara Cattadori, Annalisa Turco, Laura Scelsi, Andrea Maria D'Armini, Claudia Raineri, Mauro Acquaro, Luigi Oltrona Visconti, Carlo Pellegrini, Stefano Pelenghi, and S Ghio
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Calcineurin Inhibitors ,Population ,Urology ,Renal function ,Nephrotoxicity ,Postoperative Complications ,Maintenance therapy ,medicine ,Humans ,Everolimus ,Renal Insufficiency ,education ,Heart transplantation ,Transplantation ,education.field_of_study ,Drug Substitution ,business.industry ,Middle Aged ,Mycophenolic Acid ,Calcineurin ,Treatment Outcome ,Heart Transplantation ,Female ,Surgery ,business ,Immunosuppressive Agents ,Glomerular Filtration Rate ,medicine.drug - Abstract
Background There is little evidence on the long-term effects of calcineurin inhibitor (CNI) withdrawal and substitution with everolimus and mycophenolate mofetil in maintenance therapy of patients who have received heart transplants and have concurrent CNI nephrotoxicity. Aims of this study were to evaluate the progression of renal dysfunction after discontinuation of CNIs and to monitor for major adverse events after therapy change. Methods Data from 41 patients who underwent heart transplant and have different degrees of renal dysfunction (estimated glomerular filtration rate [eGFR] Results In 52% of patients, there was a clear improvement in renal function (10.5 mL/min/1.73 m2 of extra eGFR on average). The former were characterized by less advanced age and a short time from the heart transplant. The echocardiographic parameters showed a significant reduction in septum thickness (11.58 ± 2 mm vs 10.29 ± 2 mm; P = .0001) and in left ventricle posterior wall thickness (10.74 ± 1 mm vs 9.74 ± 1 mm; P = .0004). The incidence of late acute rejection and cardiac allograft vasculopathy was similar in our population compared to literature data. Conclusions A therapeutic switch from CNIs to everolimus and mycophenolate mofetil can improve renal function in patients with CNI nephrotoxicity, especially in those with a shorter time period from transplantation, without exposing them to a higher incidence of late acute rejection and cardiac allograft vasculopathy.
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- 2020
49. Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy
- Author
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Jean-Philippe Lafrance, Patrick du Souich, Roy Hajjar, Lucie Boutin, Naoual Elftouh, Vincent Pichette, Pierre Y. Garneau, Gabriel Chan, and Josée Michaud
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Urology ,030230 surgery ,Mycophenolate ,Tacrolimus ,Intestinal absorption ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Gastrectomy ,Weight loss ,medicine ,Humans ,Immunology and Allergy ,Pharmacology (medical) ,Prospective Studies ,Prospective cohort study ,Transplantation ,business.industry ,Mycophenolate Sodium ,Immunosuppression ,Middle Aged ,Mycophenolic Acid ,Obesity, Morbid ,Kidney Failure, Chronic ,Female ,Laparoscopy ,medicine.symptom ,business ,Immunosuppressive Agents - Abstract
Laparoscopic sleeve gastrectomy induces weight loss via the creation of a restrictive gastric tube for early satiety and is associated with an accelerated gastric transit time. A prospective, single-dose pharmacokinetic study was performed, prior to and after laparoscopic sleeve gastrectomy, for tacrolimus, extended-release tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium. The study included 12 morbidly obese patients in chronic renal failure. The median decrease in body mass index was 8.8 kg/m2 with an excess body weight loss of 54.9%. The AUC24 of all drugs were increased after laparoscopic sleeve gastrectomy by 46%, 55%, 77%, and 74%, respectively. The maximum concentrations were increased for tacrolimus, extended-release tacrolimus, and mycophenolate mofetil by 43%, 46%, and 65%. The apparent total clearances were decreased for tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium by 36%, 57%, and 38%. Laparoscopic sleeve gastrectomy can be associated with significant changes in pharmacokinetics of the drugs evaluated. The mechanism is likely decreased apparent drug clearance due to an increased drug exposure (from a more distal site of intestinal absorption with decreased intestinal metabolism), or decreased clearance (liver metabolism). Adapting the monitoring of immunosuppression will be important to avoid overdosing and potential side effects.
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- 2020
50. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial
- Author
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Ronan Foley, Tony Panzarella, Irwin Walker, Genevieve Gallagher, Thomas J. Nevill, John Kuruvilla, Gizelle Popradi, Stephanie J. Lee, Cynthia L. Toze, Stephen Couban, David Szwajcer, Jean Roy, Holly Kerr, John Moore, Gerald M. Devins, Félix Couture, Kirk R. Schultz, and Mohamed Elemary
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,T-Lymphocytes ,Graft vs Host Disease ,Kaplan-Meier Estimate ,Disease-Free Survival ,Tacrolimus ,law.invention ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Transplantation, Homologous ,Cumulative incidence ,Patient Reported Outcome Measures ,Aged ,Antilymphocyte Serum ,Bone Marrow Transplantation ,Peripheral Blood Stem Cell Transplantation ,business.industry ,Standard treatment ,Hazard ratio ,Hematology ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,3. Good health ,Anti-thymocyte globulin ,Transplantation ,Methotrexate ,Treatment Outcome ,Graft-versus-host disease ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Cyclosporine ,Female ,Unrelated Donors ,business ,Immunosuppressive Agents ,Follow-Up Studies ,030215 immunology - Abstract
Previous trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a long-term timepoint as the primary endpoint.This was a randomised, open-label, multicentre, phase 3 trial done at ten centres in Canada and one in Australia. Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma), were between 16 and 70 years of age, eligible for transplantation with a Karnofsky score of at least 60, and received an unrelated donor (fully matched or one-locus mismatched at HLA-A, HLA-B, HLA-C, or DRB1 loci) graft following myeloablative or non-myeloablative-reduced intensity conditioning. Patients were randomly assigned to receive anti-thymocyte globulin 4·5 mg/kg plus standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) or standard GVHD prophylaxis alone. The primary endpoint, freedom from immunosuppressive therapy without resumption at 12 months, was previously reported. Here we report on the prespecified 24-month analysis. Analyses were per-protocol, excluding those patients who did not proceed to transplantation. This trial is registered as ISRCTN 29899028 and NCT01217723, status completed.Between June 9, 2010, and July 8, 2013, we recruited and randomly assigned 203 eligible patients to receive anti-thymocyte globulin (n=101) or no additional treatment (n=102) along with standard GVHD prophylaxis. 7 (3%) patients did not receive a transplant and were excluded from the analysis. 38 (38%) of 99 evaluable patients in the anti-thymocyte globulin plus GVHD prophylaxis group were free from immunosuppressive therapy at 24 months compared with 18 (19%) of 97 patients in the standard GVHD prophylaxis group (adjusted odds ratio [OR] 3·49 [95% CI 1·60–7·60]; p=0·0016). At 24 months, the cumulative incidence of relapse was 16·3% (95% CI 8·9–23·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 17·5 (9·9–25·1) in the standard GVHD prophylaxis group (p=0·73) and non-relapse mortality was 21·2% (95% CI 13·2–29·2) versus 31·3% (21·9–40·7; p=0·15). The cumulative incidence of chronic GVHD at 24 months was 26·3% (95% CI 17·5–35·1) in the anti-thymocyte globulin group and 41·3% (31·3–51·3) in the standard GVHD prophylaxis group (p=0·032). Overall survival at 24 months was 70·6% (95% CI 60·6–78·6) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 53·3% (42·8–62·8) in the standard GVHD prophylaxis group (adjusted hazard ratio [HR] 0·56, 95% CI [0·35–0·90]; p=0·017). Symptoms of chronic GVHD by the Lee Scale were more prevalent in the standard GVHD prophylaxis group, with scores of 13·27 (SD 10·94) in the anti-thymocyte globulin plus GVHD prophylaxis group and 20·38 (SD 14·68) in the standard GVHD prophylaxis group (p=0·040). Depressive symptoms were more prominent in the standard GVHD prophylaxis group, the mean Center for Epidemiological Studies Depression scale (CES-D) scores were 10·40 (SD 9·88) in the anti-thymocyte globulin group and 14·62 (SD 12·26) in the standard GVHD prophylaxis group (p=0·034). Serious adverse events (CTCAE grade 4 or 5) occurred in 38 (38%) patients in the anti-thymocyte globulin group and in 49 (51%) in the standard GVHD prophylaxis group, the most common being infection and GVHD. One patient in the anti-thymocyte globulin plus GVHD prophylaxis group died of Epstein-Barr virus hepatitis, but no deaths were attributable to anti-thymocyte globulin.The results of this prespecified 24-month analysis suggest that pretreatment with anti-thymocyte globulin provides clinically meaningful benefits when added to standard GVHD prophylaxis in patients undergoing unrelated donor transplantation, including decreases in use of immunosuppressive therapy, chronic GVHD and its symptoms, depressive symptoms, and improved overall survival. Anti-thymocyte globulin should be included in the preparative regimens of patients with haematological malignancies selected for unrelated donor transplantation.Canadian Institutes of Health Research and Sanofi.
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- 2020
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