Mortality and cardiovascular risk comparison between kidney transplant recipients and CKD patients with equivalent renal function.

La maladie rénale chronique(MRC) s’associe à un très haut risque cardiovasculaire(CV), et les maladies CV représentent après greffe une des principales causes de décès avec greffon fonctionnel. Le débit de filtration glomérulaire(DFG) influe sur le risque CV. L’objectif de ce travail était de comparer pour la 1ère fois patients MRC et transplantés rénaux(TR) à même niveau de DFG sur 1) le risque de mortalité; 2) le niveau de rigidité aortique (évaluée par la vitesse de l’onde de pouls carotido-fémorale, CF-VOP). Le 3ème objectif visait à comparer l’évolution de la pression pulsée (PP) selon le devenir rénal (dialyse ou transplantation rénale préemptive, TRP) des patients MRC inscrits préemptivement sur liste de greffe. Méthodes. Ce travail est basé sur l’analyse de plusieurs cohortes. Pour l’objectif 1, les données étaient issues de CKD-REIN et DIVAT. CKD-REIN est une cohorte prospective réalisée dans 40 consultations de néphrologie en France, incluant 3033 patients avec MRC modérée à sévère. Le registre DIVAT recense prospectivement les données de patients transplantés de 8 centres français, notre étude concernait le registre nantais. L’objectif 2 était étudié au sein d’une partie de la cohorte prospective parisienne NephroTEST de patients MRC adressés pour bilan standardisé au service des Explorations Fonctionnelles de l’Hôpital Tenon (Paris), et de la cohorte rétrospective TransplanTEST de patients TR également évalués dans ce service (168 patients TR à l’Hôpital Foch-Suresnes). Pour ces objectifs, les patients TR et MRC étaient appariés sur un score de propension qui incluait notamment le DFG. Le 3ème objectif concernait les patients de CKD-REIN inscrits préemptivement sur liste de greffe: le niveau de PP et son évolution étaient comparés selon le type de suppléance rénale (SR) initié au cours du suivi (dialyse ou TRP). Résultats. Dans notre 1ère étude, la TR était associée à une augmentation du risque de mortalité relativement aux patients MRC appariés (HR: 2,6[1,54- 4,56], p=0,001 après ajustement sur l’âge, le DFG et le ratio protide/creatinine urinaire). L’augmentation du risque apparaissait davantage liée à une fréquence accrue des infections sévères et cancers qu’à une augmentation du risque CV. Il n’a pas été mis en évidence de différence concernant le risque de survenue de ≥ 1 événement CV non létal au cours du suivi (HR : 0,8[0,44-1,50], p=0,501). Dans la 2ème étude, les patients TR présentaient à 12 mois de la greffe une CF-VOP significativement plus basse que les patients MRC appariés (10,1m/s vs 11,0m/s, p=0,008), contrairement à l’évaluation réalisée à 3 mois de greffe (10,5m/s vs 11,0m/s, p=0,242). L’amélioration survenant au cours de la 1ère année de greffe conférait aux patients TR évalués à 12 mois un moindre niveau de rigidité aortique relativement aux patients MRC de même DFG. Après ajustement sur l’âge, la pression artérielle moyenne, le DFG mesuré, l’indice de masse corporelle, le statut diabétique et le niveau de PTH sérique, la TR s’associait à une réduction de 60% du risque de CF-VOP>10,6m/s (médiane) à 12 mois de la greffe (OR: 0,4[0,23-0,68]). Enfin, les résultats (préliminaires) de notre 3ème étude n’ont pas retrouvé d’association entre le type de SR et les modalités d’évolution de la PP au cours des 6 mois suivant l’initiation, chez les patients inscrits préemptivement sur liste de greffe. La dégradation du DFG dans l’année précédant la SR était plus rapide dans le groupe ayant évolué vers la dialyse (à étiologies de MRC comparables). Conclusion. Nos résultats confortent l’idée qu’une remise à zéro du risque de mortalité et d’événement CV des patients MRC n’est pas rendu possible, même après TR, de même qu’un retour au niveau d’un patient MRC comparable. Les complications CV post TR apparaissent différer de celles des patients MRC de même DFG. Les stratégies de prévention et de ralentissement de la progression de la MRC doivent par conséquent constituer une priorité en néphrologie.Chronic kidney disease (CKD) is associated with a very high cardiovascular (CV) risk, and CV disease is one of the main causes of death with a functioning transplant after kidney transplantation. Glomerular filtration rate (GFR) influences CV risk. The objective of this work was to compare for the first time CKD-patients and renal transplant recipients (RTR) with similar GFR level: 1) on the risk of overall mortality; 2) on aortic stiffness level (assessed by carotid-femoral pulse wave velocity, CF-PWV), a CV risk biomarker. The third objective was to compare pulse pressure (PP) and its evolution according to renal replacement therapy modality (dialysis or preemptive renal transplantation, PRT) in CKD patients pre-emptively registered on the kidney transplant waiting list.Methods. This work is based on the analysis of several cohorts. For the first objective, data came from CKD-REIN and DIVAT. CKD-REIN is a French prospective cohort performed in 40 nephrology consultations, including 3033 patients with moderate to severe CKD. The DIVAT register prospectively collects data of transplant recipients from 8 French centers, our study focused on the Nantes’ register. The second objective was studied in part of the prospective Parisian NephroTEST cohort of CKD-patients who were referred to the Physiology Unit of Tenon Hospital (Paris) for a one-day standardized evaluation, and of the RTR TransplanTEST cohort (retrospective cohort of 168 TR patients at Foch Hospital-Suresnes) evaluated in the same Physiology Unit. For these two objectives, RTR and CKD-patients were matched on a propensity score which included GFR among others. For the third objective, CKD-REIN patients who were pre-emptively registered on the kidney transplant waiting list were compared on PP level and on its evolution, according to the renal replacement therapy (RRT) modality initiated during the follow-up (dialysis or PRT). Results. In our first study, RTR was associated with an increased risk of overall mortality relative to the matched CKD-patients (HR: 2.6 [1.54-4.56], p=0.001 after adjusting for age, GFR and protide/creatinine urinary ratio). The increased risk appeared to be more related to an increased frequency of severe infections and neoplasms than to an increased CV risk. There was no difference between the two groups concerning the occurrence of at least one non-fatal CV event during the follow-up (HR: 0.8 [0.44-1.50], p=0.501). On the other hand, in the second study, RTR presented a significantly lower CF-PWV at 12-months after kidney transplant than the CKD-matched patients (10.1m/s vs 11.0m/s, p=0.008), unlike the evaluation performed at 3 months post-transplant (10.5m/s vs 11.0m/s, p=0.242). The improvement occurring within the 1st year of RT conferred to RTR assessed at 12 months a lower aortic stiffness level in comparison to the CKD-matched patients with similar GFR. After adjustment for age, mean arterial pressure, measured GFR, body mass index, diabetic status and serum PTH level, RT was associated with a 60% reduction in the risk of CF-VOP > 10.6m/s (median) at 12 months after RT (OR: 0.4 [0.23-0.68]). Finally, our latest (preliminary) results (third study) did not find any association between the RRT modality and PP evolution within the 6 months following RRT initiation in patients who were pre-emptively registered on the kidney transplant waiting list. The GFR decline in the year prior to RRT initiation was faster in-group of patients who initiate dialysis (with comparable CKD etiologies). Conclusion. Our results support the idea that, RT does not offset the excess mortality risk observed in CKD patients. At the same level of GFR, post-TR CV complications appear to be different from CV complications in CKD patients. Therefore, we believe that prevention and slowing CKD progression strategies must remain a priority in nephrology

Does kidney transplantation influence a form of discrimination for antihypertensive drugs prescriptions?

International audienc

Belatacept and Long-Term Outcomes in Kidney Transplantation

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Uremic Toxins and Clinical Outcomes: The Impact of Kidney Transplantation

Non-transplanted and transplanted patients with chronic kidney disease (CKD) differ in terms of mortality and the risk of clinical events. This difference is probably due to the difference of both traditional and non-traditional risk factors. Uremic retention solutes may constitute important non-traditional risk factors in this population. In the present review, we selected a set of uremic toxins that have been associated with harmful effects, and are an appealing target for adjuvant therapy in CKD. For each toxin reviewed here, relevant studies were selected and the relationship with hard clinical outcomes of uremic toxins were compared between non-transplanted CKD patients and transplanted patients taking into account the level of glomerular filtration rate in these two situations

The Case | Epistasis and urolithiasis

International audienceA 26-year-old woman was referred for recurrent urolithiasis. The first manifestation occurred 3 years before, followed by recurrent acute episodes. She underwent one ureteral stent placement, one shock wave lithotripsy, and at last a flexible ureteroscopy that allowed to retrieve all the remaining stones. She had no other medical history with the exception of paroxysmal tachycardia, poor dairy intake in her diet and did not take any medication interfering with calcium or phosphate homeostasis. Regarding her family history, her mother had also recurrent renal colic due to urolithiasis. Morphoconstitutional analysis revealed a stone made of calcium phosphate and to a lesser extent calcium oxalate, in concentric layers. According to infrared spectra analysis, the stone consisted mainly of calcium phosphate: 56% carbonated apatite, 20% octacalcium phosphate pentahydrate (OCP), 12% calcium oxalate monohydrate, 10% calcium oxalate dihydrate and 2% proteins

Difference in Profiles of the Gut-Derived Tryptophan Metabolite Indole Acetic Acid between Transplanted and Non-Transplanted Patients with Chronic Kidney Disease

International audienceBackground: Uremic toxins have emerged as potential mediators of morbidity and mortality in patients with chronic kidney disease (CKD). Indole-3-acetic acid (IAA, a tryptophan-derived uremic toxin) might be a useful biomarker in patients with CKD. The objectives of the present study were to (i) describe IAA concentrations in a cohort of non-transplanted patients with CKD and a cohort of transplanted patients with CKD, and (ii) investigate the possible relationship between IAA levels and adverse outcomes in the two cohorts. Methods: Levels of free and total IAA were assayed in the two prospective CKD cohorts (140 non-transplanted patients and 311 transplanted patients). Cox multivariate analyses were used to evaluate the association between IAA levels and outcomes (mortality, cardiovascular events, and graft loss). Results: In the non-transplanted CKD cohort, free and total IAA increased progressively with the CKD stage. In the transplanted CKD cohort, free and total IAA levels were elevated at the time of transplantation but had fallen substantially at one-month post-transplantation. Indole acetic acid concentrations were lower in transplanted patients than non-dialysis non-transplanted patients matched for estimated glomerular filtration rate (eGFR), age, and sex. After adjustment for multiple confounders, the free IAA level predicted overall mortality and cardiovascular events in the non-transplanted CKD cohort (hazard ratio [95% confidence interval]: 2.5 [1.2-5.1] and 2.5 [1.3-4.8], respectively). In the transplanted CKD cohort, however, no associations were found between free or total IAA on one hand, and mortality, CV event, or graft survival on the other. Conclusion: We demonstrated that levels of IAA increase with the CKD stage, and fall substantially, even normalizing, after kidney transplantation. Free IAA appears to be a valuable outcome-associated biomarker in non-transplanted patients, but-at least in our study setting-not in transplanted patients

Less arterial stiffness in kidney transplant recipients than chronic kidney disease patients matched for renal function

International audienceBackgroundChronic kidney disease is associated with a high cardiovascular risk. Compared with glomerular filtration rate–matched CKD patients (CKDps), we previously reported a 2.7-fold greater risk of global mortality among kidney transplant recipients (KTRs). We then examined aortic stiffness [evaluated by carotid–femoral pulse wave velocity (CF-PWV)] and cardiovascular risk in KTRs compared with CKDps with comparable measured glomerular filtration rate (mGFR).MethodsWe analysed CF-PWV in two cohorts: TransplanTest (KTRs) and NephroTest (CKDps). Propensity scores were calculated including six variables: mGFR, age, sex, mean blood pressure (MBP), body mass index (BMI) and heart rate. After propensity score matching, we included 137 KTRs and 226 CKDps. Descriptive data were completed by logistic regression for CF-PWV values higher than the median (>10.6 m/s).ResultsAt 12 months post-transplant, KTRs had significantly lower CF-PWV than CKDps (10.1 versus 11.0 m/s, P = 0.008) despite no difference at 3 months post-transplant (10.5 versus 11.0 m/s, P = 0.242). A lower occurrence of high arterial stiffness was noted among KTRs compared with CKDps (38.0% versus 57.1%, P < 0.001). It was especially associated with lower mGFR, older age, higher BMI, higher MBP, diabetes and higher serum parathyroid hormone levels. After adjustment, the odds ratio for the risk of high arterial stiffness in KTRs was 0.40 (95% confidence interval 0.23–0.68, P < 0.001).ConclusionsAortic stiffness was significantly less marked in KTRs 1 year post-transplant than in CKDps matched for GFR and other variables. This observation is compatible with the view that the pathogenesis of post-transplant cardiovascular disease differs, at least in part, from that of CKD per se

Higher mortality risk among kidney transplant recipients than among estimated glomerular filtration rate-matched patients with CKD-preliminary results

International audienceBackground. Although kidney transplantation prolongs survival relative to dialysis, it is associated with a higher death rate than in the general population. The objective of the present study was to assess and compare the risk of mortality and frequency of non-lethal cardiovascular (CV) events in kidney transplant recipients (KTRs) beyond 1year after successful transplantation versus patients with chronic kidney disease (CKD) using propensity score-matched analysis of estimated glomerular filtration rate (eGFR) and other parameters. Methods. After propensity score matching, we studied 340 KTRs from the French Donnees Informatisees et Validees en Transplantation cohort and 605 non-transplant patients with CKD (CKDps) from the French Chronic Kidney Disease-Renal Epidemiology and Information Network cohort. The mean standard deviation eGFR was 4213 and 41 +/- 12mL/min/ 1.73m(2), respectively (P=0.649). Descriptive data were completed by a survival analysis with Cox regression models. Results. After a median follow-up period of 2.8 years (KTRs 2.0 years, CKDp 2.9 years), 71 deaths were recorded (31 and 40 in the KTR and CKD groups, respectively). Univariate analysis showed that KTRs had a significantly greater risk of mortality than CKDps. In multivariable analysis, KTRs were found to have a 2.7-fold greater risk of mortality [hazard ratio 2.7 (95% confidence interval 1.6-4.7); P=0.005]. There was no between-group difference concerning the risk of CV events (P=0.448). CV death rates in KTRs (29.0%) approximated those of CKDps (22.5%), whereas death rates due to infections were higher in KTRs (19.4% versus 10.0%). Conclusion. Beyond 1year after transplantation, KTRs, who possibly had a longer CKD history, had a significantly greater mortality risk than eGFR-matched CKDps. The excess risk was not associated with CV events