Dataset Information

Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.

ABSTRACT:

Background

The use of the immunosuppressant sirolimus in kidney transplantation has been made problematic by the frequent occurrence of various side effects, including paradoxical inflammatory manifestations, the pathophysiology of which has remained elusive.

Methods

30 kidney transplant recipients that required a switch from calcineurin inhibitor to sirolimus-based immunosuppression, were prospectively followed for 3 months. Inflammatory symptoms were quantified by the patients using visual analogue scales and serum samples were collected before, 15, 30, and 90 days after the switch.

Results

66% of patients reported at least 1 inflammatory symptom, cutaneo-mucosal manifestations being the most frequent. Inflammatory symptoms were characterized by their lability and stochastic nature, each patient exhibiting a unique clinical presentation. The biochemical profile was more uniform with a drop of hemoglobin and a concomitant rise of inflammatory acute phase proteins, which peaked in the serum 1 month after the switch. Analyzing the impact of sirolimus introduction on cytokine microenvironment, we observed an increase of IL6 and TNF? without compensation of the negative feedback loops dependent on IL10 and soluble TNF receptors. IL6 and TNF? changes correlated with the intensity of biochemical and clinical inflammatory manifestations in a linear regression model.

Conclusions

Sirolimus triggers a destabilization of the inflammatory cytokine balance in transplanted patients that promotes a paradoxical inflammatory response with mild stochastic clinical symptoms in the weeks following drug introduction. This pathophysiologic mechanism unifies the various individual inflammatory side effects recurrently reported with sirolimus suggesting that they should be considered as a single syndromic entity.

SUBMITTER: Buron F

PROVIDER: S-EPMC3538748 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.

Buron Fanny F Malvezzi Paolo P Villar Emmanuel E Chauvet Cécile C Janbon Bénédicte B Denis Laure L Brunet Maria M Daoud Sameh S Cahen Rémi R Pouteil-Noble Claire C Gagnieu Marie-Claude MC Bienvenu Jacques J Bayle François F Morelon Emmanuel E Thaunat Olivier O

PloS one 20130107 1

<h4>Background</h4>The use of the immunosuppressant sirolimus in kidney transplantation has been made problematic by the frequent occurrence of various side effects, including paradoxical inflammatory manifestations, the pathophysiology of which has remained elusive.<h4>Methods</h4>30 kidney transplant recipients that required a switch from calcineurin inhibitor to sirolimus-based immunosuppression, were prospectively followed for 3 months. Inflammatory symptoms were quantified by the patients u ...[more]

PMID: 23308138

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Dataset Information

Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.

Background

Methods

Results

Conclusions

Publications

Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.

Similar Datasets

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