Establishing targets for goal-directed anesthesia in renal transplantation: A cohort analysis of high-saliency surgical time courses.

Delayed graft function (DGF) increases morbidity and mortality in kidney transplant recipients. Operative parameters, including hemodynamic manipulation through vasopressors and fluids, can impact perfusion to the newly transplanted kidney and influence DGF incidence. We analyzed intraoperative time-series data in 5-minute intervals from kidney transplant recipient operations (N = 545) in conjunction with pretransplant characteristics and postsurgical outcomes, including DGF incidence, 60-day creatinine, and graft survival. Of the operations, 127 DGF events were captured in our cohort from a single academic transplant center (57/278 donations after brainstem death [DBDs], 65/150 donations after circulatory/cardiac death [DCDs], 5/117 live donations). In multiple regression, postanastomosis hypotension defined as mean arterial pressure (MAP) <75 mmHg was a risk factor for DGF independent of conventional predictors of DGF in DCD and DBD kidneys. DCD recipients with DGF had lower average postanastomosis MAP (DGF: 80.1 ± 8.1 mmHg vs no DGF: 76.4 ± 6.7 mmHg, P = .004). Interaction analysis demonstrated above-average doses of vasopressors and crystalloids were associated with improved outcomes when used at MAPs ≤75 mmHg, but they were associated with increased DGF at MAPs >75 mmHg, suggesting that the incidence of DGF can be highly influenced by intraoperative hemodynamic controls. This analysis of surgical time courses has identified potential new strategies for goal-directed anesthesia in renal transplantation.

Serum Apolipoprotein B and A1 Concentrations Predict Late-Onset Posttransplant Diabetes Mellitus in Prevalent Adult Kidney Transplant Recipients.

BACKGROUND: Glucose metabolism links closely to cholesterol metabolism. Posttransplant diabetes mellitus (PTDM) adversely affects posttransplant outcomes, but its risk factors in relation to cholesterol metabolism have not been fully delineated. The apolipoprotein B/A1 (Apo B/A1) ratio, which is associated with insulin resistance, has not been evaluated in kidney transplant recipients as a risk factor for PTDM. OBJECTIVE: The objective of this study was to determine whether serum apolipoprotein profiles predict late PTDM, defined as a new onset diabetes occurring greater than 3 months posttransplant. DESIGN: Retrospective chart review of a prevalent population of kidney transplant recipients. SETTING: Large transplant center in Ontario, Canada. PATIENTS: We identified 1104 previously nondiabetic adults who received a kidney transplant between January 1, 1998, and December 1, 2015, and were followed at 1 transplant center. MEASUREMENTS: Recipients provided testing for serum apolipoprotein B (Apo B) and apolipoprotein A1 (Apo A1) concentrations from 2010, either at 3 months posttransplant for new transplant recipients or the next clinic visit for prevalent recipients. Late PTDM defined using Canadian Diabetes Association criteria as occurring ≥3 months posttransplant was recorded until May 1, 2016. METHODS: All analyses were conducted with R, version 3.4.0 (The R Foundation for Statistical Computing). Comparisons were made using Student t test, Fisher exact test or chi-square test, Kaplan-Meier methodology with the logrank test, or Cox proportional hazards analysis as appropriate. Covariates for the multivariate Cox proportional hazards models of PTDM as the outcome variable were selected based on significance of the univariate associations and biological plausibility. RESULTS: There were 53 incident late PTDM cases, or 1.71 cases per 100 patient-years. Incident late PTDM differed between the highest and lowest quartiles for Apo B/A1 ratio, 2.47 per 100 patient-years vs 0.88 per 100 patient-years (P = .005 for difference). In multiple Cox regression analysis, first measured serum Apo B/A1 concentration better predicted subsequent PTDM than low-density lipoprotein cholesterol (LDL-C; hazard ratio [HR] = 7.80 per unit increase, P = .039 vs HR = 1.05 per unit increase, P = .774). Non-high-density lipoprotein cholesterol (HDL-C) concentrations also did not predict PTDM (P = .136). By contrast to Apo B, Apo A1 was protective against PTDM in statin users (HR = 0.17 per unit increase, P = .016). LIMITATIONS: Posttransplant diabetes mellitus cases occurring before apolipoprotein testing was implemented were not included in the analysis. CONCLUSIONS: Apolipoproteins B and A1 better predict late PTDM than conventional markers of cholesterol metabolism.

CONTEXTE: Le métabolisme du glucose est étroitement lié à celui du cholestérol. Le diabète sucré post-transplantation (PTDM­Post-Transplant Diabetes Mellitus) compromet l'état de santé après la greffe, mais le risque qu'il représente sur le métabolisme du cholestérol n'est toujours pas clairement défini. Le taux d'apolipoprotéine B/A1 (Apo B/A1), associé à l'insulinorésistance, n'a toujours pas été évalué en tant que facteur de risque pour le PTDM chez les receveurs d'une greffe rénale. OBJECTIF: Cette étude visait à déterminer si les profils sériques de l'apolipoprotéine sont prédicteurs d'un PTDM d'apparition tardive, soit d'un diabète se déclenchant plus de trois mois post-transplantation. TYPE D'ÉTUDE: Une étude rétrospective des dossiers médicaux d'une population prévalente de receveurs d'une greffe rénale. CADRE: Un important centre de transplantation de l'Ontario (Canada). SUJETS: L'étude porte sur 1 104 adultes non-diabétiques ayant subi une greffe rénale entre le 1er janvier 1998 et le 1er décembre 2015 et ayant été suivis dans un centre de transplantation. MESURES: À partir de 2010, les sujets se sont soumis à une épreuve mesurant les concentrations sériques d'Apo B et Apo A1 trois mois post-greffe pour les nouveaux receveurs ou lors de la prochaine consultation en clinique pour les receveurs prévalents. La survenue d'un PTDM d'apparition tardive, soit au minimum trois mois post-greffe selon le critère de l'Association canadienne du diabète, a été enregistrée jusqu'au 1er mai 2016. MÉTHODOLOGIE: Toutes les analyses ont été menées avec le logiciel R (R Foundation for Statistical Computing version 3.4.0). Selon le cas, les comparaisons ont été effectuées par le test t de Student, le test de Fisher exact, le test de chi-deux, la méthode de Kaplan-Meier avec le test de Mantel-Haenzel ou l'analyse de régression aléatoire proportionnelle de Cox. Les covariables du modèle multivarié de régression aléatoire proportionnelle de Cox avec le PTDM comme variable résultat ont été choisies en fonction de l'importance des associations univariées et de la plausibilité biologique. RÉSULTATS: On a répertorié 53 nouveaux cas de PTDM d'apparition tardive, soit 1,71 cas par 100 années-patient. Le nombre de nouveaux cas de PTDM d'apparition tardive différait entre le quartile le plus élevé et le quartile le plus bas pour le taux d'Apo B/A1, avec 2,47 par 100 années-patient et 0,88 par 100 années-patient respectivement (P = 0,005 pour la différence). Selon l'analyse par régression multivariée de Cox, la première mesure de la concentration d'Apo B/A1 s'est avérée un meilleur prédicteur d'un PTDM subséquent que la mesure de LDL-C (RR à 7,80 par augmentation d'une unité pour Apo B/A1, P = 0,039 contre 1,05 par augmentation d'une unité pour LDL-C, P = 0,774). Les taux de cholestérol non HDL n'ont pas non plus prédit un PTDM (P = 0,136). Contrairement à Apo B, Apo A1 protégeait contre le déclenchement d'un PTDM chez les utilisateurs de statines (RR: 0,17 par augmentation d'une unité, P = 0,016). LIMITE: Les cas de PTDM survenus avant que l'épreuve d'apolipoprotéine ne soit mise en œuvre n'ont pas été inclus dans cette analyse. CONCLUSION: Les apolipoprotéines B et A1 ont mieux prédit la survenue du PTDM d'apparition tardive que les marqueurs traditionnels du métabolisme du cholestérol.

Pre-Transplant Left Ventricular Geometry and Major Adverse Cardiovascular Events After Kidney Transplantation.

BACKGROUND Preventing major adverse cardiovascular events (MACE) after kidney transplantation motivates pre-transplant cardiac evaluation that includes two-dimensional transthoracic echocardiography (TTE). The relationship of relative wall thickness (RWT) to left ventricular mass index (LVMI) in predicting post-transplant MACE is unclear. MATERIAL AND METHODS In this multi-ethnic Canadian single-center cohort study, we identified 1063 adults undergoing pre-transplant TTE within 1 year pre-transplant and with minimum 6 months of post-kidney transplant follow-up for MACE, defined as a composite of coronary revascularization, myocardial infarction, stroke, and cardiac death. Left ventricular hypertrophy (LVH, >131 g/m² in men and >100 g/m² in women) and increased RWT (>0.45) were a priori used to define normal (no LVH, normal RWT), concentric remodeling (no LVH, increased RWT), eccentric hypertrophy (LVH, normal RWT), and concentric hypertrophy (LVH, increased RWT). RESULTS There were 134 MACE over 3577 patient-years of post-transplant follow-up. Both LVH (HR 1.58, p=0.022) and high RWT (HR 1.44, p=0.041) predicted MACE in multivariate survival regression analysis independently of common pre-transplant MACE risk factors. Concentric remodeling, concentric hypertrophy, and eccentric hypertrophy all increased the risk for MACE (4.44, 5.05, and 5.55 events per 100 patient-years, respectively) versus normal echocardiography (2.71 events per 100 patient-years, all p<0.05 for difference). In Cox interactive regression analysis, LVMI and RWT were independently associated with MACE (p=0.015, p=0.025) and significantly interacted (p=0.008). CONCLUSIONS LV geometric parameters beyond LVH alone can assist post-transplant prognostication in kidney transplant candidates.