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Tremor induced by Calcineurin inhibitor immunosuppression: a single-centre observational study in kidney transplanted patients

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Abstract

Introduction

Tremor is the most frequent and disabling neurological side effect under Calcineurin inhibitor-induced immunosuppression, but no studies have defined its phenomenology, severity, distribution, the impact on quality of life, as well as of other neurological symptoms associated.

Methods

126 consecutive kidney-transplanted patients, under treatment with Cyclosporin A, Tacrolimus and non-Calcineurin inhibitors, within therapeutic range, were enrolled. Participants underwent a deep neurological examination by two blinded to the treatment raters, and a blood sampling to assess plasmatic immunosuppressant level and nephrological function tests. Tremor and cerebellar signs were scored according to the Fahn–Tolosa–Marin and the SARA scale. Parkinsonism was excluded applying the UPDRS (part III).

Results

Tremor was more common and severe in the Tacrolimus group, similar to impairment in ADL. Regardless of treatment, tremor involved both upper and lower limbs and was activated by action, but in about 50% of cases presented in action and rest condition. Plasmatic level of Tacrolimus was higher in patients with tremor than in those without, while cholesterol was significantly lower. Cerebellar and neuropathic signs were overall mild and were not significantly different across the three groups comparing patients with and without tremor.

Conclusions

Non-Calcineurin inhibitors such as Sirolimus have the lowest propensity to induce tremor and with a milder severity, while Calcineurin inhibitors, especially Tacrolimus, the highest, and regardless of the formulation. Plasmatic concentration of Tacrolimus was higher in tremulous patients; further research needs to validate the role of cholesterol plasmatic concentration in predicting the occurrence of tremor in patients on Tacrolimus.

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References

  1. Morgan JC, Sethi KD (2005) Drug-induced tremors. Lancet Neurol 4:866–876

    Article  PubMed  CAS  Google Scholar 

  2. Elias WJ, Shah BB (2014) Tremor. JAMA 311:948–954

    Article  PubMed  CAS  Google Scholar 

  3. Kim WR, Lake JR, Smith JM et al (2017) OPTN/SRTR 2015 annual data report: liver. Am J Transplant 17:174–251

    Article  PubMed  Google Scholar 

  4. Kandaswamy R, Stock PG, Gustafson SK et al (2017) OPTN/SRTR 2015 annual data report: pancreas. Am J Transplant 17:117–173

    Article  PubMed  Google Scholar 

  5. Colvin M, Smith JM, Skeans MA et al (2017) OPTN/SRTR 2015 annual data report: heart. Am J Transplant 17:286–356

    Article  PubMed  Google Scholar 

  6. Hart A, Smith JM, Skeans MA et al (2017) OPTN/SRTR 2015 annual data report: kidney. Am J Transplant 17:21–116

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ekberg H, Tedesco-Silva H, Demirbas A et al (2007) Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 357:2562–2575

    Article  PubMed  CAS  Google Scholar 

  8. Azzi JR, Sayegh MH, Mallat SG et al (2013) calcineurin inhibitors: 40 years later, can’t live without. J Immunol 191:5785–5791

    Article  PubMed  CAS  Google Scholar 

  9. Anghel D, Tanasescu R, Campeanu A et al (2013) Neurotoxicity of immunosuppressive therapies in organ transplantation. Maedica 8:170–175

    PubMed  PubMed Central  Google Scholar 

  10. Bechstein WO (2000) Neurotoxicity of calcineurin inhibitors: impact and clinical management. Transpl Int 13:313–326

    Article  PubMed  CAS  Google Scholar 

  11. Pirsch JD, Miller J, Deierhoi MH et al (1997) A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation 63:977–983

    Article  Google Scholar 

  12. Bulatova N, Yousef AM, Al-Khayyat G, Qosa H (2011) Adverse effects of tacrolimus in renal transplant patients from living donors. Curr Drug Saf 6:3–11

    Article  PubMed  Google Scholar 

  13. Langone A, Steinberg SM, Gedaly R et al (2015) Switching study of kidney transplant patients with tremor to LCP-Tacro (STRATO): an open-label, multicenter prospective phase 3b study. Clin Transplant 29:796–805

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Fahn S, Tolosa E, Concepcion M (1993) Clinical rating scale for tremor. In: Jankovic J, Tolosa E (eds) Parkinson’s disease and movement disorders, 2nd edn. Williams and Wilkins, Baltimore, pp 271–280

    Google Scholar 

  15. Schmitz-Hübsch T, du Montcel ST, Baliko L et al (2006) Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 66:1717–1720

    Article  PubMed  Google Scholar 

  16. England JD, Gronseth GS, Franklin G et al (2005) Distal symmetric polyneuropathy: a definition for clinical research. Report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 64:199–207

    Article  PubMed  CAS  Google Scholar 

  17. Moccia M, Pellecchia MT, Erro R et al (2010) Restless legs syndrome is a common feature of adult celiac disease. Mov Disord 25:877–881

    Article  PubMed  Google Scholar 

  18. Elble RJ (1998) Tremor in ostensibly normal elderly people. Mov Disord 13:457–464

    Article  PubMed  CAS  Google Scholar 

  19. Paul F, Muller J, Christe W et al (2004) Postural hand tremor before and following liver transplantation and immunosuppression with cyclosporine or tacrolimus in patients without clinical signs of hepatic encephalopathy. Clin Transplant 18:429–433

    Article  PubMed  Google Scholar 

  20. Wijdicks EF (2001) Neurotoxicity of immunosuppressive drugs. Liver Transpl 7:937–942

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. R. Erro, Ruggero Bacchin, G. Zaza and M. Tinazzi contributed equally to this work.

Authors and Affiliations

  1. Section of Neurology, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Piazzale L.a. Scuro 10, 37134, Verona, Italy

    R. Erro, Ruggero Bacchin, F. Magrinelli, C. Geroin, G. Squintani & M. Tinazzi

  2. Renal Unit, Department of Medicine, University of Verona, P.le A. Stefani 1, 37126, Verona, Italy

    P. Tomei, A. Lupo & G. Zaza

Authors
  1. R. Erro
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  2. Ruggero Bacchin
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  3. F. Magrinelli
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  4. P. Tomei
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  5. C. Geroin
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  6. G. Squintani
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  7. A. Lupo
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  8. G. Zaza
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  9. M. Tinazzi
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Contributions

ER: conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article, revising it critically for important intellectual content, and final approval of the version to be submitted. BR: acquisition of data, analysis and interpretation of data, drafting the article, and revising it critically for important intellectual content. MF: acquisition of data, and drafting the article. TP: acquisition of data, analysis and interpretation of data, drafting the article and revising it critically for important intellectual content. GC: acquisition of data. SG: acquisition of data. LA: final approval of the version to be submitted. ZG: conception and design of the study, acquisition of data, analysis and interpretation of data, drafting the article and revising it critically for important intellectual content. TM: conception and design of the study, drafting the article, critical revision for important intellectual content and final approval of the version to be submitted.

Corresponding author

Correspondence to Ruggero Bacchin.

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Ethical standards

The study has been approved by the ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Erro, R., Bacchin, R., Magrinelli, F. et al. Tremor induced by Calcineurin inhibitor immunosuppression: a single-centre observational study in kidney transplanted patients. J Neurol 265, 1676–1683 (2018). https://doi.org/10.1007/s00415-018-8904-x

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  • DOI: https://doi.org/10.1007/s00415-018-8904-x

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