tacrolimus and Metabolism--Inborn-Errors

Cardiovascular disease (CVD) is an important cause of morbidity and mortality after liver transplantation (LT). Serum adiponectin levels inversely correlate with CVD-related outcomes, but the relationship between hypoadiponectinemia and CVD after LT is unknown. Thus, the aim of the present study was to prospectively evaluate this relationship in LT recipients (LTR).. LTR were prospectively enrolled (N = 130) between January 1, 2012, and January 1, 2014. Baseline adiponectin levels were drawn at enrollment and patients were followed for CVD events. Hypoadiponectinemia was defined as serum adiponectin <10 µg/mL. The primary endpoint was a composite CVD outcome consisting of myocardial infarction, angina, need for coronary revascularization, stroke, or cardiac death.. The mean age was 58 ± 11 years and prevalence of obesity, diabetes, and dyslipidemia was 40%, 35%, and 40%, respectively. A total of 20 CVD events were noted, after median follow up of 45 months. Hypoadiponectinemia was significantly associated with future risk of CVD events (hazard ratio, 3.519; 95% confidence interval, 1.180-10.499, P = 0.024). This association was independent of traditional CVD risk factors including age, gender, obesity, hypertension, diabetes, and choice of immunosuppression.. Hypoadiponectinemia is a strong independent predictor of future cardiovascular events in LTR, which can be incorporated in clinical practice to assess CVD risk assessment after LT.

Topics: Adiponectin; Aged; Cardiovascular Diseases; Cyclosporine; Diabetes Complications; Dyslipidemias; End Stage Liver Disease; Female; Humans; Immunosuppression Therapy; Insulin Resistance; Liver Transplantation; Male; Metabolism, Inborn Errors; Middle Aged; Obesity; Proportional Hazards Models; Prospective Studies; Risk Assessment; Tacrolimus; Transplant Recipients; Treatment Outcome

Several studies have shown that calcineurin may play a critical role in the signalling of cardiac hypertrophy in various experimental models.. To elucidate whether calcineurin is involved in cardiac hypertrophy due to energy metabolic disorder by using the juvenile visceral steatosis (JVS) mouse, which is a murine model of systemic carnitine deficiency.. Cardiac hypertrophy in JVS mice (C3H strain) progresses gradually after birth and is present until eight weeks of age. In this study, calcineurin activity in JVS mice increased significantly at four weeks of age (the developing stage of cardiac hypertrophy) compared with age-matched control mice. Treatment with calcineurin inhibitor FK506 (0.5 or 1.0 mg/kg/day) from the age of four to eight weeks attenuated cardiac hypertrophy without beneficially affecting cardiac function. Gene expression, accompanied by cardiac hypertrophy, was also suppressed by the FK506 treatment.. The activation of calcineurin is involved in the development of cardiac hypertrophy in the JVS mouse, and calcineurin inhibition may be useful for reducing cardiac hypertrophy.

Topics: Animals; Blood Pressure; Cachexia; Calcineurin; Calcineurin Inhibitors; Cardiomegaly; Diabetes Mellitus; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression; Hypertension; Infections; Metabolism, Inborn Errors; Mice; Mice, Inbred C3H; Myocardium; Reference Values; Renal Insufficiency; Tacrolimus