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Risques concurrents et modèles multi-états dans les analyses de survie en dialyse

Abstract : In survival analysis, a competing risk is an event that hinders the observation of the event of interest (usually death). If the probability of a competing risk depends on the probability of the event of interest, then it can not be treated as censoring. Patients with ESRD can be treated with hemodialysis, peritoneal dialysis and renal transplantation. These treatments are complementary and patients can move from one treatment modality to another. The dependence between changes in treatment modality and the probability of death has not been studied and these changes are censored in survival analysis.Objectives: To analyze the dependence between the probability of death in dialysis and kidney transplant, and the probability of death on peritoneal dialysis and transfer to hemodialysis. We demonstrate the negative consequences if this dependence is not taken into account in the survival analysis. Methods: (1) We compared estimates of event probability obtained by the Kaplan-Meier method and Kalbfleisch and Prentice on 383 consecutive indicent patients treated by peritoneal dialysis in Lille. (2) We analyzed data on 7318 incident patients undergoing hemodialysis in France from the national registry REIN. We used a multistate model to analyze the influence of inclusion on the transplant waiting list on the probability of death on dialysis. (3) In a cohort of 2790 patients aged over 65 and treated with peritoneal dialysis from the registry of the French Language Peritoneal Dialysis (RDPLF), we analyzed the factors against transfer-indication in HD taking into account death as competing risk using the Fine and Gray model. This analysis was complemented by a survey conducted among 55 nephrologists practicing Peritoneal dialysis in France.Results: (1) The Kaplan-Meier method systematically overestimated the probability of death due to violation of the assumption of independence between death and competing risks. This method does not appear valid in the analyzes of survival on dialysis. The method of Kalbfleisch and Prentice was valid but the interpretation of cumulative impacts must take into account all the competing risks. (2) Kidney transplantation is a competing risk depending on the probability of dying patients. Patients on the transplant waiting list had a risk of death significantly lower than other patients, after adjustment for age and comorbidity. (3) The transfer is a risk in hemodialysis competitor who seems to depend on the probability of dying patients. Indeed, age and comorbidities were both risk factors and death factors against transfer-indications for hemodialysis. Moreover, most nephrologists who responded to our survey reported that limited life expectancy could be an indication to the transfer-cons.Conclusion: In cohort studies of patients with ESRD, the survival analyzes should take into account changes in treatment because they are competing risks dependent on the probability of death. Our work has shown that multi-state models are statistical tools that enable flexible to adequately represent the interdependence between the different modalities of treatment for peritoneal dialysis, hemodialysis, kidney transplantation and death.
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Jean-Baptiste Beuscart. Risques concurrents et modèles multi-états dans les analyses de survie en dialyse. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2012. Français. ⟨NNT : 2012LIL2S019⟩. ⟨tel-00879223⟩

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