Tocilizumab-Based Treatment of Microvascular Inflammation in Kidney Transplant Recipients: A Retrospective Study Johan Noble, Giorgia Comai, Valeria Corredetti, Reda Laamech, Celine Dard, Thomas Jouve, Diane Giovannini, Audrey Le Gouellec, Shivani Wadnerkar, Paolo Cravedi, Della Apuzzo, Daniele Vetrano, Marco Busutti, Chiara Abenavoli, Paolo Malvezzi, Lionel PE Rostaing, Gaetano Lamanna Transplant International, 2025 Chronic-active antibody mediated rejection (caAMR) is the leading causes of long-term kidney graft failure. Tocilizumab (TCZ), an anti-IL-6 receptor antibody, has been suggested as a treatment, but data are conflicting. We retrospectively studied consecutive adult kidney transplant recipients with caAMR or microvascular inflammation (MVI) without Donor-Specific Antibodies (DSA) and without C4d deposition (MVI + DSA-C4d-), who received TCZ as first-line therapy in two European centers. Estimated glomerular filtration rate (eGFR) and DSA were assessed one-year before and after TCZ initiation. The study included 64 patients who received TCZ between July 2018 and September 2023. The eGFR trajectory significantly decreased after TCZ treatment (−1.2 ± 0.2 vs. 0.03 ± 0.2 mL/min/1.73 m2/month pre- vs. post-TCZ, respectively; p = 0.001). The percentage of patients with DSA decreased from 63.9% to 38.9% (p < 0.001), and the average MFI decreased from 9,537 to 7,250 (p = 0.001). In multivariate analysis, younger age (OR = 0.95, p = 0.02), MVI + DSA-C4d- phenotype (OR = 5.2, p = 0.01), and lower chronic glomerulopathy score (OR = 4.5, p = 0.02) were associated with TCZ response (trajectory ≥0 after TCZ). Patient survival was 98.4%, and graft survival was 93.7% at one-year. First-line TCZ therapy for caAMR or MVI + DSA-C4d- is associated with an improvement of eGFR trajectories, reduced DSA numbers and MFI and histological inflammation in glomeruli. These data suggest a potential benefit of TCZ in these settings.
Renal Benefits of CO2 as a Contrast Media for EVAR Procedures: New Perspectives on 1 Year Outcomes Marco Busutti, Alice Sensoni, Andrea Vacirca, Chiara Abenavoli, Chiara Donadei, Anna Laura Croci Chiocchini, Matteo Righini, Giorgia Comai, Alessia Pini, Gianluca Faggioli, Enrico Gallitto, Gaetano La Manna, Mauro Gargiulo Journal of Endovascular Therapy, 2024 Background and Objectives: Endovascular aneurism repair (EVAR) is a minimally invasive alternative to open surgery for the treatment of abdominal aortic aneurysm. Iodine contrast medium (ICM) is considered the gold standard, at the high price of related nephrotoxicity and allergic reactions. Carbon dioxide (CO2) has been suggested as an alternative non-nephrotoxic contrast media agent. We aimed to evaluate the safety and the renal impact of the administration of CO2, compared with ICM in EVAR procedures. Design, Setting, Participants, and Measurements: We retrospectively reviewed data of patients who underwent EVAR at the Vascular Surgery Department of the Sant’Orsola Hospital in Bologna. Estimated glomerular filtration rate (eGFR) was evaluated before intervention, immediately after and at 12 months. Results: In total, 22 patients received CO2 and low-dose ICM (CO2 Group) and 22 received standard ICM (Control Group), matched for clinical characteristics and renal function at the time of procedure. Pre and post-operative renal function values (eGFR) were compared between the two groups: in the immediate post-operative the group treated with CO2 and low-dose ICM globally showed a slight improvement in renal function (mean eGFR +5.10%±3.2), meanwhile the group treated with standard dose of ICM presented a significant worsening of renal function compared with pre-procedure values (mean eGFR −9.65%±4). Incidence of post-contrast acute kidney injury (PC-AKI) was 9% in the CO2 group vs 27% in the Control group. At 12 months, the renal impairment was significantly greater in the ICM group than in the CO2 group (mean eGFR decrease −19.2%±11.1 and −7.40%±3.5, respectively). Conclusions: Administration of either CO2 alone or along with low-dose ICM showed to be safer than full-dose ICM alone, lowering the incidence of PC-AKI in patients undergoing EVAR. Unexpectedly, our study revealed also a significant worsening of renal function in patients treated with standard dose of ICM in 1-year follow-up, introducing the concept that acute renal damage caused by ICM could elicit a chronic injury process that affect long-term renal outcomes. Clinical Impact Evaluating the safety and the renal impact of the administration of CO2, compared to Iodinate Contrast Medium, in EVAR procedures represents a first step in order to further tayloring medical procedures on patients characteristics. Our findings can guide the clinicians and surgeons in the procedures choice, not considering only the immediate effect of ICM on renal function but also the potential long-term effects.
“Eculizumab First” in the Management of Posttransplant Thrombotic Microangiopathy Federica Maritati, Valeria Corradetti, Claudia Bini, Michele Provenzano, Vania Cuna, et al. Kidney International Reports, 2024 IntroductionPost-transplant thrombotic microangiopathy (PT-TMA) is an uncommon event that characterizes approximately 3-14% of kidney transplants (KT), and that is associated with a higher risk of delayed graft function and graft loss. PT-TMA occurs more frequently within the first three months after transplant and can be a manifestation of de novo disease or the recurrence of previous atypical hemolytic uremic syndrome (aHUS). Abnormalities in complement regulation genes could explain the increased susceptibility of some patients to PT-TMA. Eculizumab is a humanized monoclonal antibody that inhibits the formation of the membrane attack complex C5b-9. The aim of this study is to evaluate the efficacy of eculizumab as treatment for PT-TMA.MethodsWe retrospectively analyzed clinical records of 45 KT patients who received eculizumab immediately after the clinical diagnosis of PT-TMA.ResultsKidney biopsy was performed in 91.1% of patients and complement genetic study in 64.4%. 85.4% of kidney biopsies showed signs of TMA; genetic analysis revealed one pathogenetic variant, two variants of uncertain significance, one likely benign variant, 8 risk polymorphisms, 27 risk haplotypes.After two weeks from the treatment starting, hemoglobin and platelets significantly increased. A remarkable improvement in kidney function was also observed. After six months, 28.8% of patients had a complete renal recovery while 44.4% had a partial recovery.ConclusionThis is, to our knowledge, the largest series of KT patients with PT-TMA treated with eculizumab. These data suggest that eculizumab is associated with a normalization of hemolysis indices and an important and progressive improvement of graft function.
Autosomal Dominant Polycystic Kidney Disease: Extrarenal Involvement Matteo Righini, Raul Mancini, Marco Busutti, Andrea Buscaroli International Journal of Molecular Sciences, 2024 Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder, but kidneys are not the only organs involved in this systemic disorder. Individuals with the condition may display additional manifestations beyond the renal system, involving the liver, pancreas, and brain in the context of cystic manifestations, while involving the vascular system, gastrointestinal tract, bones, and cardiac valves in the context of non-cystic manifestations. Despite kidney involvement remaining the main feature of the disease, thanks to longer survival, early diagnosis, and better management of kidney-related problems, a new wave of complications must be faced by clinicians who treated patients with ADPKD. Involvement of the liver represents the most prevalent extrarenal manifestation and has growing importance in the symptom burden and quality of life. Vascular abnormalities are a key factor for patients’ life expectancy and there is still debate whether to screen or not to screen all patients. Arterial hypertension is often the earliest onset symptom among ADPKD patients, leading to frequent cardiovascular complications. Although cardiac valvular abnormalities are a frequent complication, they rarely lead to relevant problems in the clinical history of polycystic patients. One of the newest relevant aspects concerns bone disorders that can exert a considerable influence on the clinical course of these patients. This review aims to provide the “state of the art” among the extrarenal manifestation of ADPKD.
Identification of asymptomatic Leishmania infection in patients undergoing kidney transplant using multiple tests Alessandro Deni, Alessandra Mistral De Pascali, Margherita Ortalli, Emma Balducelli, Michele Provenzano, Francesca Ferrara, Marco Busutti, Gaetano La Manna, Lorenzo Zammarchi, Alessandro Bartoloni, Leonardo Caroti, Ana Victoria Ibarra-Meneses, Eugenia Carrillo, Giorgia Comai, Stefania Varani International Journal of Infectious Diseases, 2024 OBJECTIVES: In immunocompromised patients, asymptomatic Leishmania infection can reactivate, and evolve to severe disease. To date, no test is considered the gold standard for the identification of asymptomatic Leishmania infection. A combination of methods was employed to screen for Leishmania infection in patients undergoing kidney transplant (KT). METHODS: We employed polymerase chain reaction for the detection of parasitic DNA in peripheral blood, Western blot to identify serum immunoglobulin G and whole blood assay to detect cytokines/chemokines after stimulation of whole blood with parasitic antigen. RESULTS: One-hundred twenty patients residing in Italy were included in the study at the time of KT. Each patient that tested positive to at least one test was considered as Leishmania positive. Fifty out of 120 patients (42%) tested positive for one or more tests. The detection of specific cell-mediated response (32/111, 29%) was the most common marker of Leishmania infection, followed by a positive serology (24/120, 20%). Four patients (3%) harbored parasitic DNA in the blood. CONCLUSION: Our findings underline the high prevalence of asymptomatic Leishmania infection in patients undergoing KT in Italy, who are potentially at-risk for parasite reactivation and can benefit from an increased vigilance. Understanding the clinical relevance of these findings deserves further studies.
Safety and Efficacy of Vedolizumab in Kidney Transplant Recipients With Crohn's Disease Marco Busutti, Olga Baraldi, Clara Valentina Porcu, Gianluca Samele, Anita Campus, Valeria Grandinetti, Claudia Bini, Michele Provenzano, Nikolas Dussias, Fernando Rizzello, Paolo Gionchetti, Gaetano La Manna, Giorgia Comai Kidney International Reports, 2023 Crohn’s disease (CD) and ulcerative colitis are chronic and idiopathic inflammatory bowel diseases, characterized by gastrointestinal symptoms such as abdominal pain, fecal urgency, and diarrhea1,2; and extra intestinal manifestations that may involve almost any organ including the kidney. The most common renal extra intestinal manifestations are nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis, and amyloidosis. In addition, kidney damage in patients with CD may result from dehydration, long-term malnutrition, anemia, and side-effects of medical therapy.
Using machine learning to predict antibody response to SARS-CoV-2 vaccination in solid organ transplant recipients: the multicentre ORCHESTRA cohort Maddalena Giannella, Manuel Huth, Elda Righi, Jan Hasenauer, Lorenzo Marconi, Angelina Konnova, Akshita Gupta, An Hotterbeekx, Matilda Berkell, Zaira R. Palacios-Baena, Maria Cristina Morelli, Mariarosa Tamè, Marco Busutti, Luciano Potena, Elena Salvaterra, Giuseppe Feltrin, Gino Gerosa, Lucrezia Furian, Patrizia Burra, Salvatore Piano, Umberto Cillo, Mara Cananzi, Monica Loy, Gianluigi Zaza, Francesco Onorati, Amedeo Carraro, Fiorella Gastaldon, Maurizio Nordio, Samir Kumar-Singh, Jesús Rodríguez Baño, Tiziana Lazzarotto, Pierluigi Viale, Evelina Tacconelli Clinical Microbiology and Infection, 2023
Relationship between Immune Response to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines and Development of Breakthrough Infection in Solid Organ Transplant Recipients: The CONTRAST Cohort Cecilia Bonazzetti, Beatrice Tazza, Dino Gibertoni, Zeno Pasquini, Natascia Caroccia, Francesca Fanì, Giacomo Fornaro, Renato Pascale, Matteo Rinaldi, Beatrice Miani, Chiara Gamberini, Maria Cristina Morelli, Mariarosa Tamé, Marco Busutti, Giorgia Comai, Luciano Potena, Laura Borgese, Elena Salvaterra, Tiziana Lazzarotto, Luigia Scudeller, Pierluigi Viale, Maddalena Giannella, Michela Di Chiara, Maria Eugenia Giacomini, Oana Vatamanu, Lorenzo Marconi, Clara Solera Horna, Caterina Campoli, Michele Bartoletti, Linda Bussini, Fabio Trapani, Luciano Attard, Milo Gatti, Antonio Gramegna, Gaetano La Manna, Valeria Grandinetti, Marcello Demetri, Simona Barbuto, Chiara Abenavoli, Giovanni Vitale, Laura Turco, Matteo Ravaioli, Matteo Cescon, Valentina Bertuzzo, Paola Messina, Alessandra Trombi, Marco Masetti, Paola Prestinenzi, Mario Sabatino, Laura Giovannini, Aloisio Alessio, Antonio Russo, Maria Francesca Scuppa, Giampiero Dolci, Gianmaria Paganelli, Liliana Gabrielli, Matteo Pavoni, Marta Leone, Federica Lanna, and Clinical Infectious Diseases, 2023 Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients is associated with poorer antibody response (AbR) compared with non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) has yet to be assessed. Methods Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV-2 vaccination during a 1-year period (February 2021 – January 2022), end of follow-up April 2022. Patients were tested for AbR at multiple time points. The primary end-point was BI (laboratory-confirmed SARS-CoV-2 infection ≥14 days after the second dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization, and BI states were obtained for each type of graft and vaccination sequence using multistate survival analysis. Then, multivariable logistic regression was performed to analyze the risk of BI related to AbR levels. Results 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received 3 vaccine doses. The first 2 consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively. For the third dose, mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed the lowest probability of immunization (0.418) and the highest of BI (0.323); all mRNA-1273 vaccine sequences showed the highest probability of immunization (0.732) and the lowest of BI (0.098). Risk of BI was higher for non–high-level AbR, younger age, and shorter time from transplant. Conclusions SOT patients with non–high-level AbR and shorter time from transplantation and heart recipients are at highest risk of BI.
Renal Vessel Extension With Cryopreserved Vascular Grafts: Overcoming Surgical Pitfalls in Living Donor Kidney Transplant Guido Fallani, Lorenzo Maroni, Chiara Bonatti, Giorgia Comai, Marina Buzzi, Vania Cuna, Francesco Vasuri, Francesca Caputo, Enrico Prosperi, Federico Pisani, Beatrice Pisillo, Ludovica Maurino, Federica Odaldi, Valentina Rosa Bertuzzo, Francesco Tondolo, Marco Busutti, Chiara Zanfi, Massimo Del Gaudio, Gaetano La Manna, Matteo Ravaioli Transplant International, 2023
A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome Marina Vivarelli, Manuela Colucci, Mattia Algeri, Federica Zotta, Francesco Emma, Ines L’Erario, Marco Busutti, Stefano Rota, Chiara Capelli, Martino Introna, Marta Todeschini, Federica Casiraghi, Annalisa Perna, Tobia Peracchi, Andrea De Salvo, Nadia Rubis, Franco Locatelli, Giuseppe Remuzzi, Piero Ruggenenti Jci Insight, 2023
Wide Range Applications of Spirulina: From Earth to Space Missions Giacomo Fais, Alessia Manca, Federico Bolognesi, Massimiliano Borselli, Alessandro Concas, Marco Busutti, Giovanni Broggi, Pierdanilo Sanna, Yandy Marx Castillo-Aleman, René Antonio Rivero-Jiménez, Antonio Alfonso Bencomo-Hernandez, Yendry Ventura-Carmenate, Michela Altea, Antonella Pantaleo, Gilberto Gabrielli, Federico Biglioli, Giacomo Cao, Giuseppe Giannaccare Marine Drugs, 2022
Evaluation of the Kinetics of Antibody Response to COVID-19 Vaccine in Solid Organ Transplant Recipients: The Prospective Multicenter ORCHESTRA Cohort Maddalena Giannella, Elda Righi, Renato Pascale, Matteo Rinaldi, Natascia Caroccia, Chiara Gamberini, Zaira R. Palacios-Baena, Giulia Caponcello, Maria Cristina Morelli, Mariarosa Tamè, Marco Busutti, Giorgia Comai, Luciano Potena, Elena Salvaterra, Giuseppe Feltrin, Umberto Cillo, Gino Gerosa, Mara Cananzi, Salvatore Piano, Elisa Benetti, Patrizia Burra, Monica Loy, Lucrezia Furian, Gianluigi Zaza, Francesco Onorati, Amedeo Carraro, Fiorella Gastaldon, Maurizio Nordio, Samir Kumar-Singh, Mahsa Abedini, Paolo Boffetta, Jesús Rodríguez-Baño, Tiziana Lazzarotto, Pierluigi Viale, Evelina Tacconelli, and Microorganisms, 2022
Current Perspectives in ABO-Incompatible Kidney Transplant Federica Maritati, Claudia Bini, Vania Cuna, Francesco Tondolo, Sarah Lerario, Valeria Grandinetti, Marco Busutti, Valeria Corradetti, Gaetano La Manna, Giorgia Comai Journal of Inflammation Research, 2022
Chronic kidney disease Francesca Mencarelli, Marco Busutti, Giovanni Montini Pediatric Urology Contemporary Strategies from Fetal Life to Adolescence, 2015