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Introduction: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have greatly improved outcomes in persons with CF (pwCF); however, there is still significant heterogeneity in clinical responses, particularly with regard to respiratory infection and inflammation. Exogenous administration of ketones has profound systemic anti-inflammatory effects and produces several nutrient-signaling and metabolic effects that may benefit multiple organ systems affected in pwCF. This pilot study was designed to determine the feasibility of administration of a ketone monoester (KME) to increase circulating D-beta hydroxybutyrate concentrations (D-βHB) and to improve subjective measures of CF-specific quality of life and markers of inflammation in serum and sputum in adults with CF. Methods: Fourteen participants receiving modulator therapy were randomized to receive either KME (n = 9) or placebo control (PC, n = 5) for 5–7 days during hospitalization for treatment of acute pulmonary exacerbation or as outpatients under standard care. Results: The KME was well tolerated, with only mild reports of gastrointestinal distress. D-βHB concentrations increased from 0.2 ± 0.1 mM to 1.6 ± 0.6 mM in the KME group compared to 0.2 ± 0.0 to 0.3 ± 0.1 in the PC group (p = 0.011) within 15 min following consumption and remained elevated, relative to baseline, for over 2 h. Pulmonary function was not altered after single- or short-term KME administration, but participants in the KME group self-reported higher subjective respiratory scores compared to PC in both cases (p = 0.031). Plasma inflammatory markers were not statistically different between groups following the short-term (5–7 d) intervention (p > 0.05). However, an exploratory analysis of plasma pre- and post-IL-6 concentrations was significant (p = 0.028) in the KME group but not PC. Sputum IFNγ (p = 0.057), IL-12p70 (p = 0.057), IL-1β (p = 0.100), IL-15 (p = 0.057), IL-1α (p = 0.114), and MPO (p = 0.133) were lower in the KME group compared to PC but did not achieve statistical significance. Conclusions: With the emerging role of exogenous ketones as nutrient signaling molecules and mediators of metabolism, we showed that KME is well tolerated, increases circulating D-βHB concentrations, and produces outcomes that justify the need for large-scale clinical trials to investigate the role of KME on whole-body and tissue lipid accumulation and inflammation in pwCF. [ABSTRACT FROM AUTHOR]

A meta-analysis of randomized clinical trials (RCT) was done to determine the relative risk (RR) of acute kidney injury (AKI) with the use of mammalian target of rapamycin (mTOR) inhibitors. Citations from PubMed/Medline, clinical trials.gov, package inserts and abstracts from major conferences were reviewed to include RCTs comparing arms with or without mTOR inhibitors. The RR of all grade AKI in patients taking mTOR inhibitors compared to patients not on mTOR inhibitors was 1.55 (95% CI: 1.11 to 2.16, P=0.010). There was no significant difference in the risk of high-grade AKI for the two groups (RR=1.29, P=0.118, 95% CI: 0.94 to 1.77). There was no significant difference in the incidence rates for either all grade or high-grade AKI between the two groups. There was no publication bias and the trials were of high quality per Jadad scoring.