Impact of 3 Major Maintenance Immunosuppressive Protocols on Long-term Clinical Outcomes: Result of a Large Multicenter Italian Cohort Study Including 5635 Renal Transplant Recipients

Caletti, Chiara; Ferraro, Pietro Manuel; Corvo, Alice; Tessari, Gianpaolo; Capelli, Irene; Minetti, Enrico; Gesualdo, Loreto; Girolomoni, Giampiero; Boschiero, Luigino; Lupo, Antonio; Zaza, Gianluigi

doi:10.1016/j.transproceed.2018.02.209

Cited by 4 publications

(3 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of mTOR-i instead of antimetabolites may not significantly alter major clinical outcomes. The use of mTOR-i can be a valuable pharmacological tool to minimize complications of CNI and achieve adequate immunosuppression [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Immunological Results of Long-Term Use of Mammalian Target of Rapamycin (mTOR) Inhibitors and Its Effects on Renal Graft Functions

et al. 2021

View full text Add to dashboard Cite

Background Calcineurin inhibitor drugs (CNI), which are the basis of immunosuppression in kidney transplantation, contribute to renal graft loss, with increased morbidity and mortality due to their potentially harmful effects on the renal graft, cardiovascular system, and tumor pathology. For this reason, the mammalian target of rapamycin inhibitors (mTORi) such as sirolimus (SRL) and everolimus (EVE) has been preferred more frequently, as they are associated with fewer complications and longer graft function. Material/Methods We enrolled 89 adult renal transplant patients (37 patients on mTORi and 52 on CNI) who had similar age, sex, primary renal disease, dialysis type, post-transplant follow-up period, and donor type. We analyzed and compared the data between patients using mTORi for longer than 5 years and those using CNI regarding pre- and post-transplant panel reactive antibody (PRA), and donor-specific antibody (DSA), as well as post-transplantation and current graft functions. Results Although those using mTORi for more than 5 years had significantly higher mismatch rates ( P =0.024) than those using CNI, there was no significant change in PRA and DSA levels. Transplant time was longer in mTORi users ( P =0.025). The switch time to mTORi in patients ranged from 0 to 19 years, but the average was 4 years. As expected, actual spot urine protein/creatinine was significantly higher in those using mTORi ( P =0.009). Diabetes mellitus (DM) and BK virus nephropathy (BKVN) rates were significantly higher due to switching the regimen from CNI to mTORi. Conclusions Long-term use of mTORi does not appear to be an immunological problem.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunological Results of Long-Term Use of Mammalian Target of Rapamycin (mTOR) Inhibitors and Its Effects on Renal Graft Functions

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Mammalian target of rapamycin (mTOR) inhibitors are effective therapeutic option in the immunosuppression after organ transplantation. However, currently they are prescribed to 5-10% of transplant recipients [31]. This is mainly due to the high incidence of side effects requiring dose reduction or, in many cases, drug withdrawal [32].…”

Section: Discussionmentioning

confidence: 99%

High dose everolimus promotes a pro-inflammatory phenotype and facilitates the epithelial to mesenchymal transition of primary bronchial epithelial cells isolated from cystic fibrosis patients.

Granata¹,

Santoro²,

Masola³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Lung transplantation is still the best therapeutic option for cystic fibrosis (CF) patients, but, unfortunately, immunosuppressive therapies, often employed at high dosages to avoid acute rejection, may induce severe complications. In particular, patients treated with high dose of mammalian target of rapamycin inhibitors (mTOR-Is) may experience lung fibrosis (including bronchiolitis obliterans-organizing pneumonia). Although epithelial to mesenchymal transition (EMT) of airway cells has a central role in this process, the complete biological machinery is not completely clarified.Methods: In order to improve our knowledge on this process, primary bronchial epithelial cells carrying F508del mutation were treated with 5 and 100 nM everolimus (EVE) for 24 hours. Subsequently, RNA was hybridized to the Human HT-12 v3 Expression BeadChip (Illumina). Real-Time PCR was, then, used to validate microarray results and to measure major EMT biomarkers. Trans-epithelial resistance was measured by Millicell-ERS ohmmeter.Results: High dosage EVE induced a significant up-regulation of 42 genes and a down-regulation of 12 genes. After pathway analysis by Gene Set Enrichment Analysis and Ingenuity Pathway Analysis, we found that most of them were implicated in the pro-inflammatory pathway. Real-Time PCR validated these results and revealed that, in addition to pro-inflammatory genes (IL-1α, IL-8, Pim-1 Oncogene), EVE at high dosage was able to up-regulate major EMT biomarkers (such as: alpha-smooth muscle actin, connective tissue growth factor and metalloproteinase 12). In lung, EMT is the convergence point between inflammation and the progression of fibrotic damage. Additionally, EVE at this dosage reduced the trans-epithelial resistance (altering tight junction strength). In contrast, lower EVE did not trigger similar effects.Conclusions: We demonstrated that high dose EVE may trigger a pro-inflammatory/fibrotic biological machinery in bronchial epithelial cells from CF patients. Our results, although obtained in vitro, suggest that solid organ transplant recipients affected by CF should be treated with the lowest possible dose of mTOR inhibitors to minimize/avoid the onset and development of lung complications. In vivo studies might be useful to confirm our hypothesis.

show abstract

“…In the last 20 years, improvements in organ preservation, optimization of surgical techniques, progress in post-operative care, and the introduction of more effective immunosuppressive drugs have led to significant advances in long-term graft and patient survival in organ transplantation. However, most transplant recipients experience systemic complications, often induced by over-immunosuppression, including malignancies (1)(2)(3)(4)(5)(6). Skin cancers, mostly non-melanoma skin cancers (NMSC) (squamous cell carcinoma and basal cell carcinoma), represent the most common form of cancer in Caucasian solid organ transplant recipients, with a continuing increase in incidence worldwide (7,8).…”

Section: Introductionmentioning

confidence: 99%

Skin cancer in solid organ transplant recipients: still an open problem

et al. 2023

View full text Add to dashboard Cite

In the last two decades, the optimization of organ preservation and surgical techniques, and the personalized immunosuppression have reduced the rate of acute rejections and early post-transplant complications. However, long-term graft survival rates have not improved over time, and evidence suggest a role of chronic calcineurin inhibitor toxicity in this failure. Solid organ transplant recipients may develop chronic dysfunction/damage and several comorbidities, including post-transplant malignancies. Skin cancers, mostly non-melanoma skin cancers (squamous cell carcinoma and basal cell carcinoma), are the most common malignancies in Caucasian solid organ transplant recipients. Several factors, together with immunosuppression, may contribute to the susceptibility for skin cancers which, although often treatable, could be associated with a much higher mortality rate than in the general population. The rapid identification and treatment (including reduction of immunosuppression and early surgical treatments) have an important role to avoid an aggressive behavior of these malignancies. Organ transplant recipients with a history of skin cancer should be followed closely for developing new and metastatic lesions. Additionally, patient education on the daily use of sun-protective measures and the recognition of the early signs (self-diagnosis) of coetaneous malignancies are useful preventive measures. Finally, clinicians should make themselves aware of the problem and build, in every clinical follow-up center, collaborative network involving transplant clinicians, dermatologists and surgeons who should work together to easily identify and rapidly treat these complications.In this review, we discuss the current literature regarding the epidemiology, risk factors, diagnosis, preventive strategies and treatments of skin cancer in organ transplantation.

show abstract

Impact of 3 Major Maintenance Immunosuppressive Protocols on Long-term Clinical Outcomes: Result of a Large Multicenter Italian Cohort Study Including 5635 Renal Transplant Recipients

Cited by 4 publications

References 7 publications

Immunological Results of Long-Term Use of Mammalian Target of Rapamycin (mTOR) Inhibitors and Its Effects on Renal Graft Functions

Immunological Results of Long-Term Use of Mammalian Target of Rapamycin (mTOR) Inhibitors and Its Effects on Renal Graft Functions

High dose everolimus promotes a pro-inflammatory phenotype and facilitates the epithelial to mesenchymal transition of primary bronchial epithelial cells isolated from cystic fibrosis patients.

Skin cancer in solid organ transplant recipients: still an open problem

Contact Info

Product

Resources

About