ABSTRACT
Background: Protein-energy wasting (PEW) in end-stage renal disease (ESRD) patients is associated with increased morbidity and mortality, but options for treatment are limited. Growth hormone (GH) increases insulin-like growth factor 1 (IGF-1), with improved nutritional parameters, but must be given subcutaneously and does not provide normal GH secretion patterns. MK-0677, an oral ghrelin receptor agonist (GRA), maintains normal GH secretion and increases lean body mass in normal subjects; it has not been studied in dialysis patients, an essential step in assessing efficacy and safety prior to clinical trials. Methods: We performed a randomized crossover double-blind study in assessing the effect of MK-0677 versus placebo on IGF-1 levels, the primary outcome, in hemodialysis patients. In total, 26 subjects enrolled and 22 completed the 3-month crossover study. Results: The geometric mean IGF-1 was 1.07-fold greater [95% confidence interval (CI) 0.89-1.27; P = 0.718] after placebo. In patients receiving MK-0677, the geometric mean IGF-1 were 1.76-fold greater (95% CI 1.48-2.10; P < 0.001) following MK-0677. When the data were adjusted for preintervention IGF-1 concentration, the ratio of geometric means (MK-0677 relative to placebo) for the pre- versus postintervention change in the IGF-1 was 1.65 (95% CI 1.33-2.04; P < 0.001). These data demonstrate a 65% greater increase (95% CI 33-104%) in IGF-1 in MK-0677-dosed subjects compared with placebo. There were no serious adverse effects attributable to MK-0677. Conclusions: MK-0677 increased serum IGF-1 levels with minimal adverse effects in hemodialysis subjects. Studies are needed to evaluate whether long-term therapy with MK-0677 improves PEW, lean body mass, physical strength, quality of life and survival in CKD/ESRD patients.
Subject(s)
Indoles/administration & dosage , Insulin-Like Growth Factor I/analysis , Kidney Failure, Chronic/therapy , Quality of Life , Receptors, Ghrelin/agonists , Renal Dialysis , Spiro Compounds/administration & dosage , Aged , Cross-Over Studies , Double-Blind Method , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/drug therapy , Male , Middle Aged , PrognosisABSTRACT
Ecstasy (MDMA, 3,4-methylenedioxymethamphetamine) is commonly used by college-aged individuals. Ecstasy leads to feelings of euphoria, emotional empathy, and increased energy. These effects come at a significant risk for complications. Ecstasy has been associated with acute kidney injury that is most commonly secondary to nontraumatic rhabdomyolysis but also has been reported in the setting of drug-induced liver failure and drug-induced vasculitis. More common, ecstasy has led to serious hyponatremia and hyponatremia-associated deaths. Hyponatremia in these cases is due to a "perfect storm" of ecstasy-induced effects on water balance. Ecstasy leads to secretion of arginine vasopressin as well as polydipsia as a result of its effects on the serotonergic nervous pathways. Compounding these effects are the ready availability of fluids and the recommendation to drink copiously at rave parties where ecstasy is used. The effects of ecstasy on the kidney as well as therapeutic measures for the treatment of ecstasy-induced hyponatremia are presented.
