In France, therapeutic patient education is a cornerstone of posttransplant care. However, substantial variability persists in how immunosuppressive therapies are addressed across transplant centers, potentially affecting adherence and patient outcomes. To reduce this heterogeneity, the French-Speaking Society for Transplantation (Société Francophone de Transplantation) launched a national initiative to harmonize educational practices on immunosuppressive therapy. Following a national survey that highlighted inconsistent and sometimes conflicting messages delivered to patients, a multidisciplinary working group comprising transplant physicians, pharmacists, pharmacologists, nurses, and representatives of patient associations developed a practical reference guide. This guide aims to help healthcare teams deliver coherent, evidence-based messages on key aspects of immunosuppressant management. Adaptable to local workflows and patient needs, it covers 7 core domains: timing of administration; relation to meals; missed-dose management; food and drug interactions; travel across time zones; handling of dosage forms; and special situations such as vomiting or swallowing disorders. It also underscores the critical role of therapeutic drug monitoring in supporting individualized care and strengthening adherence. This nationally coordinated initiative illustrates how collaborative, cross-disciplinary efforts can enhance the quality and consistency of patient education in transplantation. Its structured approach may serve as a model for other countries seeking to optimize adherence and long-term outcomes through standardized educational practices.

Renal manifestations of secondary syphilis are rare with membranous nephropathy being the most frequently reported lesion. We report the case of a kidney-transplant recipient who presented with multiple features of secondary syphilis, including rash, cytopenia, hepatitis and acute kidney injury. Nucleic acid amplification testing for Treponema pallidum was positive in peripheral blood, urine and bone marrow. Kidney allograft biopsy revealed acute tubulointerstitial nephritis and immunohistochemical staining of renal tissue was positive for T. pallidum. The patient was successfully treated with antibiotics and corticosteroids. This case highlights a rare cause of acute kidney injury in kidney-transplant recipients and underscores the importance of considering syphilis in the differential diagnosis of unexplained renal dysfunction with hepatitis and cutaneous rash.

Calcineurin inhibitor (CNI) trough concentrations and their variability are frequently used as adherence proxies, despite limited validation. We evaluated the association between self-reported adherence and CNI exposure during the first year after kidney transplantation. We included 619 patients from two prospective French cohorts (14,829 C-0 values). Adherence was assessed using the MMAS-4 questionnaire. CNI exposure was evaluated via C-0 levels, intra-patient variability (IPV; CV threshold = 30%), and underexposure rates. Cross-sectional and longitudinal analyses were performed. No significant differences in C-0, IPV, or underexposure were observed between adherent and non-adherent patients, regardless of the CNI used or analytical approach. In longitudinal analysis, IPV was similar (31.3% [25.5-38.2] vs. 31.6% [23.6-38.9], p = 0.68), as was the proportion of patients with high IPV (55.5% vs. 51.5%, p = 0.5). At 3 years, high IPV was not significantly associated with rejection (HR 1.02 [0.67-1.55], p = 0.93). Self-reported adherence was not associated with CNI C-0 levels, IPV, or underexposure. CNI C-0 variability alone cannot reliably detect non-adherence and should not be interpreted as a standalone adherence marker. Multimodal strategies combining pharmacokinetics with validated self-report tools are needed to evaluate adherence.

BACKGROUND AND AIMS:The awareness regarding HEV infection in solid organ transplant (SOT) has increased over the last few decades after the reports of chronicity and associated complications. The aim of this study was to describe HEV outcome over a long period in a large cohort of patients undergoing SOT. APPROACH AND RESULTS:This retrospective, single-center study analyzed 6452 patients undergoing SOT followed between 2001 and 2024 and systematically screened for HEV in cases of elevated liver enzymes. Since 2016, patients undergoing SOT have also been screened for HEV at 3 and 12 months after transplantation. We assessed the incidence, natural history, treatment, and extrahepatic manifestations. HEV infection was diagnosed in 228 patients (3.53%). The incidence was significantly higher in patients undergoing liver transplant compared to others. At 3 months after HEV documentation, 65.1% developed chronic hepatitis, while 34.9% achieved spontaneous viral clearance. Tacrolimus use was independently associated with chronicity, while mycophenolic acid use was protective. Ribavirin was the main antiviral therapy, achieving a 91.5% sustained virological response rate when treatment was extended until complete serum and stool HEV RNA clearance. A minority of patients required multiple treatment courses or failed therapy, with some developing cirrhosis or dying viremic. Three patients died from decompensated HEV-related cirrhosis. HEV-associated neurological manifestations (2.2%) and glomerular diseases (3.9%) were observed, often resolving with viral clearance. CONCLUSIONS:HEV infection is frequent in SOT recipients, with significant risks of chronicity and extrahepatic complications. Ribavirin remains the cornerstone of treatment, and individualized duration improves outcomes. Screening for HEV is mandatory in patients undergoing SOT with elevated liver enzymes.

State-of-the-art immunosuppressant therapies recommend the use of induction therapy after kidney transplantation. Anti-interleukin-2 receptor antibody (basiliximab) is used for low-risk patients whereas polyclonal anti-lymphocyte sera (ALS) are recommended for medium/high-risk patients. There are two commercially available rabbit-derived ALS, namely anti-thymocyte globulin (RATG; Thymoglobulin®) and anti-lymphocyte globulin (RATLG; Grafalon®). We retrospectively compared the efficacy and safety of RATG or RATLG induction therapy in high-risk kidney transplant recipients with preformed donor specific antibodies (DSAs; n = 124). Forty-seven recipients received 1.25 mg/kg RATG for 2 to 3 days. Seventy-seven recipients were treated with 9 mg/kg RATLG on day 0 followed by 4 mg/kg RATLG for 2 to 3 days (n = 21) or a single dose of 9 mg/kg RATLG on day 0 (n = 56). Overall there were no significant differences observed between patients treated with RATG and RATLG. Similarly, no difference was observed between patients who had been given a single dose of RATLG and multiple doses of RATLG or RATG. At one year, patient and graft survival rates, acute rejection rate and type of rejection, kidney function, infections and malignancies did not differ between groups. Kidney transplant patients with preformed DSA showed similar clinical outcomes when treated with RATG or RATLG induction therapy. Polyclonal antibodies in high immunological risk kidney transplant patients.

Introduction: De novo donor-specific antibody (dnDSA) is a strong biomarker associated with the development of antibody-mediated rejection (AMR) and graft loss after kidney transplantation. This procedure is expensive; however, systematic annual screening was recommended by some national organ transplant agencies or societies even though its clinical utility was not clearly established. Methods: To address this question, we retrospectively assessed the incidence of dnDSA according to the test justification (clinically indicated or systematic) in a cohort of low-immunological risk patients, defined by being nonhuman leukocyte antigen (non-HLA)-sensitized and having no previous kidney transplants. Results: A total of 1072 patients, for whom 4611 anti-HLA tests were performed, were included in the study. During the follow-up period of 8 (interquartile range, IQR: 5-11) years, 77 recipients developed dnDSA (prevalence of 7.2%). Thirty-five of these dnDSAs (45.5%) were detected during the first year posttransplantation. In 95% of patients with dnDSA, an immunizing event was identified in their medical records. dnDSA was detected in 46 of 4267 systematic screening tests (1.08%) performed. Active and chronic AMR were frequently observed in biopsies performed after systematic DSA testing (17.9% and 15.4%, respectively). Conclusion: Our results suggest that the detection by systematic screening of dnDSA in low-immunological risk kidney transplant patients without sensitizing events is a rare event, especially after 1 year. Moreover, in real life, systematic annual screening for dnDSA, seems having a limited impact to detect AMR at an earlier stage compared to patients in whom dnDSA was detected after a clinically indicated test.

Background Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes. Methods In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis. Findings Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 044 (95% CI 023-088; p=0022), mainly explained by a protective effect on the risk of death (HR 041, 013-091; p=0042). There was no meaningful association between IAK and death-censored graft survival (073, 030-189; p=036). Interpretation In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide.

LETTER TO THE EDITOR Transpl Int, 11 April 2024 https://doi.org/10.3389/ti.2024.12628

Background.In kidney transplant recipients with positive serology (R+) for the cytomegalovirus (CMV), 2 strategies are used to prevent infection, whose respective advantages over the other are still debated. This study aimed to evaluate the cost-effectiveness and cost utility of antiviral prophylaxis against CMV versus preemptive therapy, considering CMV infection-free survival over the first year posttransplantation as the main clinical outcome. Methods.Clinical, laboratory, and economic data were collected from 186 kidney transplant patients CMV (R+) included in the cohort study (85 patients who benefited from CMV prophylaxis and 101 from preemptive therapy). Costs were calculated from the hospital perspective and quality-adjusted life years (QALYs) using the EQ5D form. Using nonparametric bootstrapping, the incremental cost-effectiveness ratio (ICER) and cost utility were estimated (euros) for each case of infection avoided and each QALY gained for 1 y, respectively. Results.Prophylaxis significantly decreased the risk of CMV infection over the first year posttransplantation (hazard ratio 0.22, 95% confidence interval = 0.12-0.37, P < 0.01). Compared with preemptive therapy, prophylaxis saved financial resources (1155 per patient) and was more effective (0.42 infection avoided per patient), resulting in an ICER = 2769 per infection avoided. Prophylaxis resulted in a net gain of 0.046 in QALYs per patient and dominated over preemptive therapy with 1422 cost-saving for 1 QALY gained. Conclusions.This study shows that CMV prophylaxis, although considered as a more expensive strategy, is more cost-effective than preemptive therapy for the prevention of CMV infections in renal transplant patients. Prophylaxis had a positive effect on quality of life at reasonable costs and resulted in net savings for the hospital.

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.

www.transplantjournal.com 549 French Recommendations for a National Competency Framework of Therapeutic Patient Education in Solid Organ Transplantation Caroline Monchaud, PharmD, PhD, Claire Villeneuve, PhD, Stéphanie Belaiche, PharmD, PhD, Marina Charbit, MD, PhD, Charlotte Colosio, MD, Pauline Houssel, MD, Aurélie Meurette, MD, Karine Nubret, MD, Adrien Tissot, MD, Marion Albouy, MD, and Laure Esposito, MD

Recent large meta-analyses suggested a poorer long-term patients' and grafts' outcomes after ABO incompatible (ABOi) living-donor kidney transplantation (LDKT) compared to ABO compatible LDKT. However, little is known about the long-term histological pattern after ABOi LDKT. We compared the histological features observed on protocol biopsies from 03/11 to 11/19 in 94 ABOi LDKT (including 14 with preformed Donor Specific Antibodies, pDSAs), 27 LDKT ABO compatible (ABOc) with pDSAs, and 21 ABOc without pDSAs) during the first five years post transplantation. During the first 5 years post-transplantation, a progression of chronic lesions (patients with a ci >0 raised from 11% to 65%, p<0.0001, patients with a ct >0 raised from 29% to 78%, p<0.0001) was observed in ABOi LDKT without pDSAs. Histological patterns of evolution were comparable to those observed in ABOc kidney transplant patients. Microvascular inflammation was lower in ABOi LDKT without pDSAs compared to those with pDSAs (ABOi or ABOc). At last follow-up, 28 months, IQR (15-48) post-transplantation, 29 patients (36%) had a severe graft dysfunction (defined by a CKD-epi eGFR < 30 mL/min/1.73m²). The donor age was a predictive factor for the development of severe kidney allograft dysfunction at last follow-up (HR= 1.05, 95% CI [1.05-1.10], p= 0.03). Hence, long-term histological analysis of ABOi LDKT shows only an increase of chronic interstitial and tubular atrophy changes, without active lesions. These data confirm that ABOi LDKT programs can be securely developed.

Background: Two doses of anti-SARS-CoV-2 mRNA-based vaccines are poorly immunogenic in solid organ transplant recipients (SOT). Methods: In total, 68 belatacept-treated SOT recipients followed at the Toulouse University Hospital were investigated. They were given three injections of the BNT162b2 mRNA COVID-19 vaccine. Their humoral response was assessed by determining anti-spike antibodies and neutralizing antibodies. The T-cell responses were assessed using an enzyme-linked immunospot assay that measured the interferon-γ produced by specific SARS-CoV-2 T-cells in a subgroup of 17 patients. Results: Only 23.5% of these patients developed a detectable anti-spike response. Moreover, the cellular and the humoral responses were well correlated. Patients with no humoral response were also without a detectable cellular response. Those belatacept-treated patients who developed an Anti-SARS-CoV-2 humoral response were younger, had been transplanted for longer, and had a higher lymphocyte count and a better glomerular filtration rate than those with no response. Finally, patients on tacrolimus plus belatacept produced a lower immune response. Conclusions: Belatacept-treated SOT recipients have a reduced immune response to anti-SARS-CoV-2 mRNA vaccination. The vaccine should be given quite separately from the belatacept infusion to improve immunogenicity. Studies to assess whether switching to another immunosuppressive regimen can improve the post-vaccination immune response would be useful.

The immunogenicity of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccine was improved by the administration of a third dose. The aim of our retrospective study was to assess the evolution of binding and neutralizing antibody concentration until 3 months after the third dose in a large cohort of solid organ transplant (SOT) patients (n = 872). At 1 month after the third dose, anti-SARS-CoV-2 antibodies were detected by means of enzyme-linked immunosorbent assay tests in 578 patients (66.3%). In a subgroup of patients, 70% (180 out of 257) had anti-SARS-CoV-2 antibody concentrations ranging from 1.2 to 18 411 binding antibody units (BAU)/ml and 48.5% (115 out of 239) had a neutralizing antibodies titer that can confer clinical protection against SARS-CoV-2. Three-hundred ninety-three patients out of the 416 (94.5%) who were seropositive at month 1 and were tested at 3 months after vaccination remained seropositive. Between months 1 and 3 after vaccination, binding and neutralizing antibodies concentrations decreased significantly. The proportion of protected patients against the SARS-CoV-2 also slightly decreased. In conclusion, this study shows that although two-third of SOT develop anti-SARS-CoV-2 antibodies after three doses, one-third of them remain weak or non-protected. It is important to measure anti-SARS-CoV-2 antibodies to define the strategy that can optimize SOT protection against SARS-CoV-2.

Letters25 May 2021Safety and Immunogenicity of Anti–SARS-CoV-2 Messenger RNA Vaccines in Recipients of Solid Organ TransplantsFREEOlivier Marion, MD, Arnaud Del Bello, MD, Florence Abravanel, PharmD, PhD, Chloé Couat, MSc, Stanislas Faguer, MD, PhD, Laure Esposito, MD, Anne Laure Hebral, MD, Jacques Izopet, PharmD, PhD, Nassim Kamar, MD, PhDOlivier Marion, MDToulouse Rangueil University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceSearch for more papers by this author, Arnaud Del Bello, MDToulouse Rangueil University Hospital and Paul Sabatier University, Toulouse, FranceSearch for more papers by this author, Florence Abravanel, PharmD, PhDToulouse Purpan University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceSearch for more papers by this author, Chloé Couat, MScToulouse Rangueil University Hospital, Toulouse, FranceSearch for more papers by this author, Stanislas Faguer, MD, PhDToulouse Rangueil University Hospital and Paul Sabatier University, Toulouse, FranceSearch for more papers by this author, Laure Esposito, MDToulouse Rangueil University Hospital, Toulouse, FranceSearch for more papers by this author, Anne Laure Hebral, MDToulouse Rangueil University Hospital, Toulouse, FranceSearch for more papers by this author, Jacques Izopet, PharmD, PhDToulouse Purpan University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceSearch for more papers by this author, Nassim Kamar, MD, PhDToulouse Rangueil University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-1341 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Recipients of solid organ transplant (SOT) are a high-risk group for severe SARS-CoV-2 infection. The mortality rate of patients with SOT during the COVID-19 pandemic has been reported to be approximately 20% (1). The anti–SARS-CoV-2 vaccines represent a hope to protect this population against this life-threatening infection.Objective: To assess the humoral response to messenger RNA (mRNA)–based vaccination in recipients of SOT.Methods: All patients with heart, kidney, liver, or pancreas transplants from the Midi-Pyrénées region (southwest France) are followed in our department. When the vaccination campaign started (7 January 2021), these patients were invited via text message, e-mail, or transplant patients' associations to be vaccinated. Patients were asked to register via a dedicated telephone number or website. They were vaccinated consecutively according to their registration date. According to the recommendations of the Francophone Society of Transplantation, anti–SARS-CoV-2 spike protein antibodies were monitored before and after vaccination. We used the SARS-CoV-2 total antibodies enzyme-linked immunosorbent assay test (Beijing Wantai Biological Pharmacy Enterprise) (80% of patients) or another validated anti–SARS-CoV-2 spike protein assay. According to French law (loi Jardé), anonymous retrospective studies do not require institutional review board approval.Findings: By 16 April 2021, 950 patients of the 2666 from our cohort had received at least 1 dose of an mRNA vaccine (BNT162b2 vaccine [Pfizer-BioNTech], n = 942; mRNA-1273 vaccine [Moderna], n = 8) and had anti–SARS-CoV-2 antibodies monitored. Fifty patients had vaccination without monitoring of antibodies, 80 patients are planned to be vaccinated within the next month, and 257 patients declined the vaccine. We had no feedback from the remaining 1329 patients.A total of 895 of the 950 patients had an available serologic screening just before the first injection. The prevalence of anti–SARS-CoV-2 antibodies was 2.1% (95% CI, 1.3% to 3.3%; n = 19 of 895). Only 5 of the 19 patients who were seropositive previously had symptomatic COVID-19. A total of 576 patients benefited from a second injection at day 28. The prevalence of anti–SARS-CoV-2 antibodies before the second injection was 6.4% (CI, 4.6% to 8.8%; n = 37 of 576).In 367 patients who had a 4-week follow-up after the second dose, the prevalence of anti–SARS-CoV-2 antibodies increased from 1.4% (CI, 0.4% to 3.2%; n = 5 of 367) at baseline to 6.3% (CI, 4.0% to 9.3%; n = 23 of 367) at day 28 and 33.8% (CI, 29.0% to 38.9%; n = 124 of 367) 1 month after the second dose (Figure). Characteristics of patients who were vaccinated with and without a 4-week follow-up after the second dose are presented in the Table.Figure. Prevalence of anti–SARS-CoV-2 antibodies at 4 wk after the second vaccine dose in all transplant patients and by type of organ transplant.Percentages with exact binomial 95% CIs are presented. Download figure Download PowerPoint Table Characteristics of Recipients of SOT With and Without a 4-Week Follow-up After 2-Dose Messenger RNA–Based VaccinationThe tolerance of mRNA vaccines was excellent, with no serious adverse events reported, except in 1 patient with a liver transplant who developed paresthesia of the lower limb. Kidney function and liver enzymes remained stable in recipients of kidney and liver transplants before and 28 days after the first dose (data not shown). One recipient of a kidney transplant presented 3 weeks after the first injection with a 50% increase in serum creatinine level related to drug-induced dehydration. The patient recovered after rehydration and reduction of diuretics. Only 1 patient, who had vaccination without the requested biological monitoring and who is not included in this report, had an acute cellular rejection.Discussion: In immunocompetent patients, mRNA vaccines have shown strong antibody response, even after a single dose (2). In immunocompromised patients, such as recipients of SOT, a weak humoral response to mRNA vaccines was reported. Boyarsky and colleagues (3) reported the appearance of specific antibodies in 17% of transplant recipients 3 weeks after a single dose of an mRNA vaccine. Recently, in a small series of patients with SOT, including mainly those who had a kidney transplant, anti–SARS-CoV-2 antibodies were detected in 37.5% to 58.8% of patients at 4 weeks after the second dose (4, 5). Our study, which included many patients with SOT, confirms a weak immunogenicity of mRNA vaccines in those who had a transplant. Recipients of liver transplant showed a better humoral response than recipients of other organs. Considering the good tolerance of mRNA vaccines, an increased antigen dose or a third vaccine dose can be proposed to improve the vaccination response in this specific population. In France, the French National Authority for Health has recently recommended offering a third dose to immunosuppressed patients.Further studies are required to assess both cellular and humoral responses to vaccines and to determine their long-term protective capacity. Meanwhile, enhanced barrier measures should be maintained, and vaccination of household members and close contacts is recommended.References1. Kates OS, Haydel BM, Florman SS, et al; UW COVID-19 SOT Study Team. COVID-19 in solid organ transplant: a multi-center cohort study. Clin Infect Dis. 2020. [PMID: 32766815] doi:10.1093/cid/ciaa1097 CrossrefGoogle Scholar2. Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 2020;586:594-599. [PMID: 32998157] doi:10.1038/s41586-020-2814-7 CrossrefMedlineGoogle Scholar3. Boyarsky BJ, Werbel WA, Avery RK, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021. [PMID: 33720292] doi:10.1001/jama.2021.4385 CrossrefGoogle Scholar4. Grupper A, Rabinowich L, Schwartz D, et al. Reduced humoral response to mRNA SARS-Cov-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. Am J Transplant. 2021. [PMID: 33866672] doi:10.1111/ajt.16615 CrossrefGoogle Scholar5. Marinaki S, Adamopoulos S, Degiannis D, et al. Immunogenicity of SARS-CoV-2 BNT162b2 vaccine in solid organ transplant recipients [Letter]. Am J Transplant. 2021. [PMID: 33864722] doi:10.1111/ajt.16607 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Olivier Marion, MD; Arnaud Del Bello, MD; Florence Abravanel, PharmD, PhD; Chloé Couat, MSc; Stanislas Faguer, MD, PhD; Laure Esposito, MD; Anne Laure Hebral, MD; Jacques Izopet, PharmD, PhD; Nassim Kamar, MD, PhDAffiliations: Toulouse Rangueil University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceToulouse Rangueil University Hospital and Paul Sabatier University, Toulouse, FranceToulouse Purpan University Hospital, Paul Sabatier University, and INSERM UMR 1291, Toulouse Institute for Infectious and Inflammatory Disease (Infinity), Toulouse, FranceToulouse Rangueil University Hospital, Toulouse, FranceDisclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M21-1341.Reproducible Research Statement: Study protocol: Available from Dr. Kamar (e-mail, kamar.n@chu-toulouse.fr). Statistical code and data set: Not available.Corresponding Author: Olivier Marion, MD, Toulouse Rangueil University Hospital, 1 Avenue du Professeur Jean Poulhès, Toulouse, France 31000; e-mail, marion.o@chu-toulouse.fr.This article was published at Annals.org on 25 May 2021. 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Keywords Antibodies COVID-19 Disclosure Liver transplantation Messenger RNA Proteins Renal transplantation Statistical data Transplantation Vaccines ePublished: 25 May 2021 Issue Published: September 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. 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Background and Purpose: Several formulations of tacrolimus are available, but evidence of the benefit of changing to the most recent formulations is lacking. Tacrolimus intra-patient variability (tacrolimus IPV) is an emerging risk factor associated with poor graft outcomes after solid organ transplantations. Here, we examined the modifications of tacrolimus IPV after switching to a different formulation of tacrolimus. Experimental Approach: We identified 353 solid organ transplant recipients that were switched in our center from immediate-release (IR-tacrolimus) or prolonged-release tacrolimus (PR-tacrolimus) to extended-release, LCP-tacrolimus (LCP-tacrolimus). Among them, 54 patients underwent at least 3 available tacrolimus blood concentrations before and after the switch, allowing us to investigate tacrolimus IPV. Key Results: The switch was considered as a safe procedure since only four of the 353 patients presented a graft rejection after the switch, and no patient was hospitalized for tacrolimus overdose. The tacrolimus IPV estimated by the coefficient of variation (CV-IPV) was stable before and after the switch to LCP-tacrolimus (CV-IPV: 29.0% (IQR 25–75 (15.5; 38.5) before and 24.0% (15.8; 36.5) after the switch, p = 0.65). Conclusion and Implications : Switching from IR- or PR-tacrolimus to LCP-tacrolimus is a safe procedure. However, the CV-tacrolimus IPV was not impacted by the change of formulation.

Background. A weak immunogenicity has been reported in solid organ transplant (SOT) recipients after 2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The aim of this retrospective study was to identify the predictive factors for humoral response in SOT patients. Methods. Three hundred and ninety-three SOT patients from our center with at least 4 wk of follow-up after 2 doses of mRNA-based vaccine were included in this study. Anti-SARS-Cov-2 spike protein antibodies were assessed before and after vaccination. Results. Anti-SARS-CoV-2 antibodies were detected in 34% of the patients: 33.7% of kidney transplant patients, 47.7% of liver transplant patients, and 14.3% of thoracic transplant patients (P = 0.005). Independent predictive factors for humoral response after vaccination were male gender, a longer period between transplantation and vaccination, liver transplant recipients, a higher lymphocyte count at baseline, a higher estimated glomerular filtration rate and receiving the tacrolimus + everolimus ± steroids combination. Conversely, the nondevelopment of anti-SARS-CoV-2 antibodies after vaccination was associated with younger patients, thoracic organ recipients, induction therapy recipients, and tacrolimus + mycophenolic acid ± steroids recipients. Conclusions. The immunosuppressive regimen is a modifiable predictive factor for humoral response to SARS-CoV-2 vaccine.