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Background: Kidney transplantation remains the first-choice treatment for end-stage renal disease (ESRD). The demand for kidney transplants is rising annually and the shortage of organs is becoming more severe. This has led to the criteria for donors being expanded to include donation after circulatory death (DCD) and poorer quality (Senior age, potential medical conditions, etc.) donations after brain death (DBD). They tend to have poorer short- and long-term outcomes. A way needs to be found to mitigate the effects of ischemia-reperfusion injury on the graft in this type of donor. Our previous studies have identified mesenchymal stromal cell (MSC) pre-exposure as a potential treatment, and we hope to further validate its effects in rat DBD and DCD models.
Objectif: We aimed to evaluate the effects of MSC pre-exposure on different types of renal grafts through the quantification of kidney injury molecule 1 (KIM-1), a highly sensitive and highly specific biomarker of kidney injury.
Methods: Two rat models (DBD and DCD) were established to obtain kidneys in different transplant situations. Two sets of serum samples, one set of urine samples and two kidneys from each rat were obtained during the procedure i: a clinical assessment of renal function (SCr, BUN) was performed. ii: Microarchitecture of grafts assessed by (immuno) histochemistry (PAS staining and KIM-1 IHC). iii: Expression of HAVCR-1 (KIM-1 gene) in tissues was assessed by q-PCR.
Conclusions: Our preliminary findings suggest that brain death and cold ischemia exacerbate the extent of kidney injury in rats, and that MSC pre-exposure may have different effects on DCD and DBD. For DBD kidneys, MSC pre-exposure may be a potential means of reducing injury. Further research is required to confirm the results. Background: La transplantation rénale reste le traitement de premier choix de l'insuffisance rénale terminale (IRT). La demande de transplantations rénales augmente chaque année et la pénurie d'organes s'aggrave. Les critères de sélection des donneurs ont donc été élargis pour inclure les dons après la mort circulatoire (DCD) et les dons après la mort cérébrale (DBD) de moins bonne qualité (âge avancé, conditions médicales potentielles, etc.). Ces derniers ont tendance à avoir de moins bons résultats à court et à long terme. Il faut trouver un moyen d'atténuer les effets des lésions d'ischémie-reperfusion sur le greffon chez ce type de donneur. Nos études précédentes ont identifié la pré-exposition aux cellules stromales mésenchymateuses (CSM) comme un traitement potentiel, et nous espérons valider davantage ses effets dans des modèles de DBD et de DCD chez le rat.
Objectif: Nous avons voulu évaluer les effets de la pré-exposition des CSM sur différents types de greffons rénaux par la quantification de kidney injury molecule 1 (KIM-1), un biomarqueur très sensible et très spécifique de lésion rénale.
Méthodes: Deux modèles de rat (DBD et DCD) ont été établis pour obtenir des reins dans différentes situations de transplantation. Deux séries d'échantillons de sérum, une série d'échantillons d'urine et deux reins de chaque rat ont été prélevés au cours de la procédure : i : une évaluation clinique de la fonction rénale (SCr, BUN) a été réalisée. ii : la microarchitecture des greffons a été évaluée par (immuno) histochimie (coloration PAS et KIM-1 IHC). iii : L'expression du HAVCR-1 (gène KIM-1) dans les tissus a été évaluée par q-PCR.
Conclusions: Nos résultats préliminaires suggèrent que la mort cérébrale et l'ischémie froide exacerbent l'étendue des lésions rénales chez les rats, et que la pré-exposition aux CSM peut avoir des effets différents selon le type de doneur. Pour les reins de DBD, la pré-exposition aux CSM peut être un moyen potentiel de réduire les lésions. Des recherches supplémentaires sont nécessaires pour confirmer ces résultats.

Nephrology --- Mesenchymal Stromal Cells --- Kidney Injury Molecule-1 --- Kidney transplantation --- Ischemia-reperfusion injury --- Ischemic preconditioning --- Sciences de la santé humaine > Urologie & néphrologie

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