Post-renal transplant malignancies: Opportunities for prevention and early screening

Turshudzhyan, Alla

doi:10.1016/j.ctarc.2020.100283

Cited by 13 publications

(11 citation statements)

References 43 publications

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“…Our results are consistent with the reports that the incidence of cancer is high in the transplant population [29][30][31]. Immunosuppressive drugs have been recognized as a major factor contributing to the increased incidence of cancer [29,30], especially virus-related cancers, in transplant recipients, suggesting that the increase is due to the loss of immune control of oncogenic viruses [29]. The incidence of malignancies might be related to the type of allograft; as reported previously, the highest incident rate of skin cancer was observed in heart transplant recipients and the lowest in liver transplant recipients [32].…”

Section: Discussionsupporting

confidence: 93%

“…As for adverse events by cyclosporine in heart transplantation, gastric cancer showed a positive association with cyclosporine in heart transplantation, and its signal score was noteworthy (ROR, 39.4; 95% CI, 16.7-93.2). Our results are consistent with the reports that the incidence of cancer is high in the transplant population [29][30][31]. Immunosuppressive drugs have been recognized as a major factor contributing to the increased incidence of cancer [29,30], especially virus-related cancers, in transplant recipients, suggesting that the increase is due to the loss of immune control of oncogenic viruses [29].…”

Section: Discussionsupporting

confidence: 92%

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Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

Niinomi¹,

Oyama²,

Inada³

et al. 2022

Cureus

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Background: Cyclosporine is widely used to prevent allograft rejection after transplantation. The purpose of this study was to clarify the adverse events profiles associated with cyclosporine in transplant patients using a spontaneous reporting system database.Methods: Retrospective pharmacovigilance disproportionality analysis was conducted using the Japanese Adverse Drug Event Report (JADER) database, with the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event.Results: The database comprised 3,327, 958, and 956 reports associated with cyclosporine in the kidney, stem cell, and heart transplant patients, respectively. Infectious and renal disorders were commonly detected in these transplant patients. The signal scores of cyclosporine for toxic nephropathy were noteworthy in the kidney (ROR: 15.1, 95% CI: 11-20.8) and stem cell (ROR, 216; 95% CI, 29.3-1593) transplantation. Cyclosporine in heart transplantation was strongly associated with gastric cancer (ROR, 39.4; 95% CI, 16.7-93.2), but not kidney or stem cell transplantation.Conclusion: It was suggested that there is a diversity in the strength of the association between cyclosporine and adverse events in the kidney, stem cell, and heart transplantation. Our results may provide useful information for treatment with cyclosporine, although further research with more data is needed.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

Niinomi¹,

Oyama²,

Inada³

et al. 2022

Cureus

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“…Relevant epidemiological data indicate that NMSC is the most common cancer in RTRs, which poses a substantial clinical and health care problem ( 5 , 6 , 8 - 10 ). Dermatological screening and identification of risk factors may help decrease the incidence rates of NMSC in RTRs ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Risk factors for non-melanoma skin cancer development in renal transplant recipients: a 40-year retrospective study in Croatia

Bašić‐Jukić¹,

Borlinić²,

Tešanović³

et al. 2022

Croat Med J

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Aim To determine the prevalence of non-melanoma skin cancer (NMSC) and disease-specific risk factors in renal transplant recipients (RTRs). Methods This retrospective cohort study enrolled 1232 RTRs (736 men) treated in University Hospital Center Zagreb over 40 years. The effect of sex, age at transplantation, geographic residence, dialysis vintage, and the type of immunosuppressive therapy on NMSC occurrence was investigated. Results The prevalence of NMSC was 6.81%. Overall, 60.7% of patients developed basal cell carcinoma (BCC) and 30.9% of patients developed cutaneous squamous cell carcinoma (cSCC). Only 8.3% developed both tumors. The BCC:cSCC ratio was 1.76:1. The risk for NMSC was 50% higher in men. Patients older than 50 years at transplantation were at greater risk for NMSC development. Residence in an area with higher ultraviolet exposure and dialysis vintage before transplantation did not influence NMSC development. Cyclosporine and azathioprine treatment conferred a greater risk for NMSC than tacrolimus or mycophenolate mofetil treatment. Conclusion RTRs are at high risk for NMSC development. Sex, age at transplantation, and type of immunosuppressive therapy play a role in tumor development.

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“…Previous studies have indicated that the metabolites of CsA have lower immunosuppressive activity than the parent drug (Christians and Sewing, 1993;Fahr, 1993). High CsA concentrations exert a stronger immunosuppressive effect, but may not improve the disease, and even induce infection and aggravate the condition (Zamora-Legoff et al, 2016;Turshudzhyan, 2021). In addition, excessive CsA exposure may increase CsA-induced neurotoxicity, including headaches, disorientation, seizures, visual disturbance, hepatotoxicity, hypertension, and gingival swelling (Sikora-Wiorkowska et al, 2019;Teshome et al, 2020;Danish et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Functional evaluation of cyclosporine metabolism by CYP3A4 variants and potential drug interactions

Kong

Gao²,

Wang³

et al. 2023

Front. Pharmacol.

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The aim of this study is to investigate the effects of CYP3A4 genetic polymorphisms on the metabolism of cyclosporine (CsA) in vitro and identify drugs that interact with CsA. An enzymatic incubation system was developed to evaluate the kinetic parameters of CYP3A4 on CsA catalysis. A total of 132 drugs were screened to identify potential drug–drug interactions. Sprague–Dawley rats were used to determine the interaction between CsA and nimodipine and nisoldipine. The metabolite AM1 was measured by ultra-performance liquid chromatography–tandem mass spectrometry. The results demonstrate that 16 CYP3A4 variants (CYP3A4.7, 8, 9, 12, 13, 14, 16, 18, 19, 23, 24, 28, 31, 32, 33, and 34) have a lower metabolic capacity for CsA, ranging from 7.19% to 72.10%, than CYP3A4.1. In contrast, the relative clearance rate of CYP3A4.5 is significantly higher than that of CYP3A4.1. Moreover, CYP3A4.20 loses its catalytic ability, and five other variants have no significant difference. A total of 12 drugs, especially calcium channel blockers, were found to remarkably inhibit the metabolism of CsA with an inhibitory rate of over 80%. Nimodipine inhibits the activity of CsA in rat liver microsomes with an IC50 of 20.54 ± 0.93 μM, while nisoldipine has an IC50 of 16.16 ± 0.78 μM. In in vivo, three groups of Sprague–Dawley rats were administered CsA with or without nimodipine or nisoldipine; the AUC(0-t) and AUC(0-∞) of CsA were significantly increased in the nimodipine group but not obviously in the nisoldipine group. Mechanistically, the inhibition mode of nimodipine on cyclosporine metabolism is a mixed inhibition. Our data show that gene polymorphisms of CYP3A4 and nimodipine remarkably affect the metabolism of CsA, thus providing a reference for the precise administration of CsA.

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Post-renal transplant malignancies: Opportunities for prevention and early screening

Cited by 13 publications

References 43 publications

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

Current Status of Adverse Event Profile of Cyclosporine in Kidney, Stem Cell, and Heart Transplantations Using the Japanese Pharmacovigilance Database

Risk factors for non-melanoma skin cancer development in renal transplant recipients: a 40-year retrospective study in Croatia

Functional evaluation of cyclosporine metabolism by CYP3A4 variants and potential drug interactions

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