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Progression de la maladie rénale chronique avant et après initiation d’un traitement de suppléance : relation avec les anomalies métaboliques et la durée de dialyse avant transplantation rénale

Abstract : Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for than three months. It leads to an increased risk of cardiovascular and infectious morbidity and mortality and reduced quality of life. CKD is recognized as a major public health problem, due to its increasing prevalence worldwide and the costs involved in its management. Identification of modifiable risk factors for CKD progression, other than hypertension and proteinuria, is essential to develop effective strategies to slow the disease progression and reduce the burden of CKD in France and worldwide. The identification of these factors is important in both children and adults, regardless of the stage of CKD. The role of hyperuricaemia has drawn attention in the nephrology community in the past two decades. However, few studies have investigated the shape of the relationship between uric acid (UA) and risk of CKD progression to identify potential critical UA thresholds, and none of these have considered longitudinal values of UA. To investigate the shape of this longitudinal relationship (OBJECTIVE 1), we used data from the prospective, French, multicenter CKD-Rein cohort that included 3033 patients with stage 3 to 5 CKD between 2013 and 2016. We first estimated for each patient its true value of UA at each time point (cUA), from all the observed repeated measures of UA using a linear mixed model. Then, we included the predicted UA value at each time point in cause-specific Cox models for initiation of kidney replacement therapy (KRT) and death before initiation of KRT. The predicted cUA was included as a time-dependent variable using a penalized spline function to detect any critical UA thresholds associated with an increased hazard of event. We found that, at any time after inclusion, the hazard of initiating KRT increased with increasing cUA, with a plateau for UA values between 6 and 10 mg/dl and a significant increase above 10 mg/dl. The association between the hazard of death before initiation of KRT and the cUA followed a U-shape, with a minimal hazard at UA 6 mg/dl and a twice higher hazard for UA values of 3 and 10 mg/dl. The association between graft failure and chronic dialysis before kidney transplantation (KT) has also been the subject of several studies. However, the results of American and European studies were inconsistent, both in children and adults. In order to investigate the association between pre-emptive KT (PKT), i.e., without prior chronic dialysis, or the duration of dialysis before KT, and graft failure (OBJECTIVE 2), we used data from the French national REIN registry covering the whole country. We investigated the association between PKT, dialysis duration and graft failure using multivariate Cox models. In both adults and children, the hazard of graft failure was approximately 2-fold higher in patients transplanted after chronic dialysis compared with patients who received PKT. We found that even short dialysis durations of less than 6 months were associated with a higher hazard of graft failure compared to patients who received PKT. These results are important for proposing care strategies to reduce the CKD burden at individual and collective level. They should encourage nephrologists to 1) monitor UA as a risk marker for CKD progression and be more stringent in controlling nephro and cardio protective factors in patients with high UA levels, and 2) register patients on the KT waiting list before initiation of dialysis.
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Submitted on : Saturday, July 2, 2022 - 1:04:00 AM
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Mathilde Prézelin-Reydit. Progression de la maladie rénale chronique avant et après initiation d’un traitement de suppléance : relation avec les anomalies métaboliques et la durée de dialyse avant transplantation rénale. Médecine humaine et pathologie. Université de Bordeaux, 2021. Français. ⟨NNT : 2021BORD0248⟩. ⟨tel-03712012⟩

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