Metabolic and Renal Effects of Mammalian Target of Rapamycin Inhibitors Treatment After Liver Transplantation: Real-Life Single-Center Experience.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors following liver transplantation (LT) are used to minimize calcineurin inhibitor (CNI)-related nephrotoxicity. Data about metabolic effects of mTOR inhibitors are still limited. AIM: This study aims to determine the renal and metabolic effects of different mTOR inhibitor-based protocols in real-life LT patients. METHODS: This is a retrospective cohort study of patients treated with mTOR inhibitors after LT. Demographics, treatment protocols, glomerular filtration rate (GFR), and metabolic parameters were collected over a period of 4 years. Initiation of blood pressure (BP), diabetes mellitus, and lipid medications was also noted. RESULTS: Fifty-two LT recipients received mTOR inhibitors. GFR improved significantly (by 1.96 mL/min/year), with greater improvement in patients with baseline renal dysfunction (+13.3 mL/min vs +4.5 mL/min at 3 years). Conversion to an mTOR inhibitor during the first post-transplant year resulted in a more durable improvement in GFR (for 4 years vs only 1 year for later conversion).No significant weight gain or new-onset diabetes mellitus was observed. However, there was some increase in total cholesterol (+7 mg/dL) and blood pressure (+2 mm Hg during the third year and +8 mm Hg in the fourth years), followed by initiation of lipid-lowering and BP medications in 25% and 13% of patients, respectively. CONCLUSIONS: Treatment with an mTOR inhibitor following LT resulted in improved kidney functions without significant negative metabolic effects such as weight gain or new-onset diabetes mellitus. This makes mTOR inhibitors a valuable immunosuppressive option in the face of the growing incidence of nonalcoholic steatohepatitis as a leading cause for LT.

The effect of various hormonal preparations and calcium supplementation on bone mass in early menopause. Is there a predictive value for the initial bone density and body weight?

OBJECTIVES: To compare the effect of various oestrogen and oestrogen/progestin preparations on bone density over a 2-year follow-up period in early postmenopausal women. SETTING: A retrospective study on 315 women followed in a menopause clinic. DESIGN: Antero-posterior lumbar spine bone densitometry was performed at baseline and between 18 and 24 months (mean 22 months) after initiation of hormone therapy. Participants were divided into six groups: women taking conjugated equine oestrogen (CEE) (n = 30); CEE plus sequential monthly medroxyprogesterone acetate (MPA) (n = 52); CEE plus sequential bimonthly MPA (n = 51); oral estradiol plus sequential monthly norethisterone acetate (n = 52); transdermal estradiol plus sequential monthly MPA (n = 30). A control group (n = 100) was composed of nonusers of hormones. RESULTS: Hormone users, as a whole (n = 215), increased their bone mineral density (BMD) by 2.9% (4.8) as compared to the controls who lost 3.5% (3.4; P < 0. 001). There were similar gains in BMD amongst the five study groups. Calcium supplementation was associated with better results in all women: users of hormones and calcium had a gain in BMD of 4.5% (4.8) compared to only 1.5% (4.5) in those on hormones but without calcium (P < 0.001); amongst the controls, women using calcium lost 1.4% (2. 4), whilst nonusers of calcium lost 3.7% (2.4; P < 0.001). A dose-response curve was found between basal BMD and the effect of hormone therapy: women with osteoporosis (T-score <75%) demonstrated the largest increase in BMD - 6.3% (4.6), osteopenia (T-score 75-85%) was associated with a gain of 3.2% (5.6), low-borderline values (T-score 86-100%) gave a modest increase of 1.3% (4.3), and those with more than average BMD values (T-score >100%) actually lost bone despite hormone treatment [-2.1% (4.1)]. CONCLUSIONS: All hormone regimens had a similar bone conserving effect. Basal BMD value may serve as a predictor for the success of treatment. Calcium supplementation should be recommended in all postmenopausal women.