Calcineurin inhibitors (CNIs) are the backbone of traditional immunosuppressive regimens for lung transplant recipients (LTR). The CNIs are both narrow therapeutic index drugs with significant interpatient and intrapatient variability that require therapeutic drug monitoring to ensure safety and effectiveness. We hypothesized that tacrolimus time-in-therapeutic range (TTR) affects acute and chronic rejection rates in LTRs. This was a single-center, observational, cross-sectional study of 292 adult LTRs. Subjects who received tacrolimus posttransplant for the first year were included. TTR was calculated at 1 year using protocol goal ranges (12-15 mg/mL months 0-6; 10-12 mg/mL for months 7-12). The primary outcome was acute cellular rejection (ACR) burden at 1 year. Chronic lung allograft dysfunction (CLAD), mortality, and infection rate were assessed as secondary outcomes at 1 year. Primary and secondary outcomes were assessed using logistic regression. Increasing TTR by 10% was associated with a significantly lower likelihood of high-burden ACR at 1 year on univariable (OR 0.46, 95% CI 0.40-0.54, P < .001) and multivariable (OR 0.64, 95% CI 0.47-0.86, P = .003) assessment, controlling for age and induction agent. Increasing TTR by 10% was also associated with lower rates of CLAD (P < .001) and mortality (P < .001) at 1 year. Prospective studies confirming these findings appear warranted.
Belatacept-based ISR appear to produce reasonable results in LTRs who fail CNI-based ISR. Larger prospective trials appear warranted in lung transplantation.
The aim of this study was to examine the relationships of short-term weight gain, weight loss, and weight cycling on the odds of developing hypertension. Normotensive middle-aged German men and women (n ¼ 12 362) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study were assigned to categories of 2-year short-term weight changes that were self-reported to have occurred prior to recruitment into the study (gain only, loss only, weight cycling, stable). After 2 years of follow-up after recruitment, 180 cases of incident essential hypertension were identified. In logistic regression models, odds ratios were estimated for the associations between short-term weight changes and risk of developing hypertension. Obesity status (BMIX30 or BMIo30 kg/m 2 ) modified the associations between short-term weight change and incidence of diagnosed hypertension. Among obese individuals, short-term weight gain occurring during the 2 years prior to recruitment (OR ¼ 2.79, 95% CI 1.19-6.56), weight loss (OR ¼ 6.74, 95% CI 2.58-17.6) and weight cycling (OR ¼ 4.29, 95% CI 1.55-11.9) were strongly positively associated with incident hypertension, adjusted for age and gender, compared to obese individuals with short-term stable weight. No significant associations between short-term weight changes and risk of diagnosed hypertension were detected among non-obese individuals. Short-term weight changes appeared to present strong risk factors for developing hypertension among obese individuals. The effect seen for weight cycling supports the hypothesis that weight cycling increases the risk of hypertension. The finding for short-term weight loss may be explained by subsequent weight regain and needs further investigation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.