Earlier decrease of FGF-23 and less hypophosphatemia in preemptive kidney transplant recipients.

BACKGROUND: Levels of fibroblast growth factor (FGF)-23, a phosphaturic hormone, increase from the early stages of CKD and are dramatically elevated in dialysis patients. Excessive FGF-23 may be involved in the hypophosphatemia and inappropriately low calcitriol levels observed after kidney transplantation (KT).This prospective observational cohort study was carried out to determine whether there are any differences in the changes in FGF-23 levels after surgery in KT recipients according to whether they were or not on dialysis before transplantation and to assess the influence of FGF-23 in the development of posttransplantation hypophosphatemia. METHODS: Consecutive KT recipients at the Hospital Clinic of Barcelona were recruited. Patients developing delayed graft function were excluded. Mineral metabolism parameters, including C-terminal fragment of FGF-23, intact parathyroid hormone, and 1,25(OH)(2)D(3), were measured in 72 KT recipients (58 on dialysis before transplantation and 14 preemptive transplant recipients) at baseline, on day 15, and at 1, 3, and 6 months after transplantation. No patients received treatment with calcimimetics, bisphosphonates, vitamin D, or phosphate supplementation during the follow-up. RESULTS: FGF-23 decreased significantly in the first month after transplantation. Baseline and FGF-23 levels within the first posttransplantation month were lower in preemptive transplant recipients than in patients on dialysis at transplantation. Serum phosphate levels were lower in dialysis patients until the third month after transplantation. Pretransplantation FGF-23 was the main predictor of posttransplantation phosphate blood levels. CONCLUSIONS: FGF-23 levels and the risk of developing posttransplantation hypophosphatemia were lower in preemptive kidney transplant recipients than in patients on dialysis before transplantation.

Interaction between serotonin 5-HT1A receptors and beta-endorphins modulates antidepressant response.

UNLABELLED: Interactions between serotonergic and the endogenous opioid systems have been suggested to be involved in the etiopathogenesis of depression and in the mechanism of action of antidepressants. Activation of serotonin 5-HT1A receptors has been shown to increase plasma beta-endorphin (beta-END) levels in animal studies and in healthy humans. OBJECTIVES: To assess interaction abnormalities between 5-HT1A receptors and the endogenous opioid system in patients with major depression and the possible modulating effect of citalopram. METHODS: The beta-END response to the 5-HT1A receptor agonist, buspirone (30 mg), was measured in 30 patients with major depression and in 30 age- and sex-matched healthy controls before and after an 8-week treatment with citalopram. Pre-treatment score of the Hamilton Rating Scale for Depression (HRSD) was >or=17. Antidepressant response was defined by a 50% decrease in the HRSD. Pre- and post-treatment maximum peak response (Deltamax) and the area under the curve (AUC) of beta-END response were compared. Three time points were measured (60, 90 and 120 min). We also examined the correlations between the beta-END response and the antidepressant response. Buspirone plasma levels were not measured. RESULTS: At baseline, beta-END response was similar in patients and controls. After 8 weeks of citalopram treatment depressed patients showed a significant decrease in the beta-END response (Deltamax: p<.001; AUC: p<.001). A significant correlation between the beta-END reduction in the response and the reduction in the HRSD score (r=.656; p<.001) was observed. CONCLUSIONS: Changes in interaction between 5-HT1A receptor system and the endogenous opioid system may play a role both in the mechanism of action and response to antidepressant drugs.

Effects of citalopram treatment on hypothermic and hormonal responses to the 5-HT1A receptor agonist buspirone in patients with major depression and therapeutic response.

Serotonin (5-HT) 5-HT1A receptor seems to play an important role in the pathophysiology of major depression and in the mechanism of action of antidepressants. In vivo function of 5-HT1A receptors can be monitored using specific pharmacological challenge tests. The present study aimed at exploring the adaptative 5-HT1A receptor changes in depressed patients before and after 8 week treatment with citalopram. The study population consisted of 30 consecutive outpatients of both sexes aged 18-45 years with major depressive disorders (DSM-IV). Basal score in the Hamilton Rating Scale for Depression (HRSD) was higher than 17. Therapeutic response was defined as a 50% decrease in the HRSD score. The hypothermic and endocrine responses (ACTH, cortisol, and prolactin) induced by the 5-HT1A receptor agonist, buspirone (30 mg p.o.) were measured. After 8 weeks on citalopram, the delta max of hypothermic response elicited by buspirone was markedly decreased (p<0.001). Patients showed a decrease in responses to ACTH (delta max p=0.005; AUC p=0.028) and cortisol (delta max p=0.05). However, the prolactin response increased (delta max p=0.02; AUC p=0.005). There was a significant correlation between the therapeutic effect and reductions of ACTH (r=0.883; p<0.001) and cortisol (r=0.610; p=0.001) responses. Changes induced by citalopram support an alteration of 5-HT1A receptors in major depression. A decrease in the overactivity of the HPA axis may be one factor associated with the response to citalopram.