Testicular function and prolactin responsiveness to TRH and cimetidine after renal transplantation.

The hypothalamic-pituitary-testicular axis and the regulation of prolactin secretion were investigated in eleven male renal transplant recipients. Mean serum levels of testosterone and estrone were normal, whereas those of androstenedione and estradiol were low. Mean basal luteinizing hormone (LH) levels were slightly elevated, but the peak responses to 50 micrograms i.v. gonadotropin-releasing hormone (GnRH) were not dissimilar from controls. Both basal and GnRH-stimulated follicle-stimulating hormone (FSH) levels were elevated (p less than 0.02-0.05) and also positively correlated with the time spent on hemodialysis (p less than 0.005-0.002). Basal prolactin (PRL) levels were normal, in all subjects. Nine out of 11 patients had a normal PRL response to Thyrotropin-releasing Hormone (TRH). However only six out of 11 had a normal response to 200 mg i.v. Cimetidine (Cim). Three subjects normally responding to TRH failed to respond to Cim. Uremic primary hypogonadism is not fully reversed by renal transplantation: a slight defect in the pituitary LH release may persist and the impairment of the tubular testicular function is left unchanged. While uremic hyperprolactinemia is corrected, the responsiveness to PRL-stimulating agents, particularly Cim, is not restored to normal, reflecting a derangement at the pituitary as well as the hypothalamic level.

Male hypogonadism of uremic patients on hemodialysis.

Primary hypogonadism occurring among uremic men on hemodialysis has been widely investigated, yet few data are available concerning the general pattern of steroidogenesis. In 161 hemodialysis patients and in 83 healthy subjects, serum levels of gonadotropins (LH and FSH), prolactin (PRL), testosterone (T), androstenedione (A), estrone (E1), estradiol (E2), and dehydroepiandrosterone-sulphate (DHEA-S) were assessed through RIA methods. Mean +/- SD hormone levels were: LH 45.6 +/- 41.1 mIU/ml, FSH 16.3 +/- 16 mIU/ml, PRL 42.4 +/- 69.1 ng/ml, A 0.83 +/- 0.27 ng/ml, E1 64.3 +/- 31.7 pg/ml, all higher than controls; T 289 +/- 125 ng/100 ml, E2 11.8 +/- 3 pg/ml, and DHEA-S 1.4 +/- 1.4 micrograms/ml, all lower than controls. The A/T and E1/E2 ratios were also higher than controls and showed a good positive linear correlation (r = 0.40; p less than 0.001) between each other. The uremic damage acts at the testis level, impairing the activity of the enzyme 17-beta-hydroxysteroid-dehydrogenase (17-OHSD), even if a derangement of the peripheral interconversion between steroids cannot be excluded.

Biofiltration vs. bicarbonate dialysis: influence on plasma volume changes and extravascular fluid mobilization.

The present study compares the effects of bicarbonate hemodialysis (Bic. HD) and biofiltration (BF), a new hemodiafiltration technique, on plasma volume (PV) changes and extravascular fluid mobilization (Vfm). Ten uremic patients underwent one experimental session of Bic. HD and, one week later, one of BF, both on the second dialysis of the week. Net ultrafiltration rate was limited to 700 ml/min. At the start of each session, whole blood volume (WBV), PV and red cell volume (RCV) were determined using 5 mu Ci of radioiodinated serum albumin (RISA). PV and Vfm were calculated at hourly intervals using a serial hematocrit method. On Bic. HD, PV increased at 60 min. then decreased at 120 and 180 min., with efficient Vfm only during the first hour. On BF, PV increased throughout treatment, with greater Vfm. It would appear that PV is better preserved in BF, on account of more efficient Vfm.

Effect of hyperprolactinemia and age on the hypogonadism of uremic men on hemodialysis.

Primary hypogonadism has been commonly reported among uremic men on hemodialysis, characterized by low testosterone levels, increased luteinizing hormone and sometimes follicle-stimulating hormone levels. Little is known about the influence of hyperprolactinemia and age on this hypogonadism. In 149 hemodialysis patients and in 60 healthy subjects the serum levels of testosterone (T), gonadotropins (LH and FSH) and prolactin (PRL) were assessed through radioimmunoassay. Mean +/- SD hormone levels were: T 274 +/- 125 ng/100 ml, lower than controls; LH 44.7 +/- 46.1 mlU/ml and FSH 17.6 +/- 18.4 mIU/ml, both higher than controls. PRL 31.3 +/- 49.4 ng/ml, higher than controls. A positive correlation between LH and FSH, a negative correlation between PRL and both T and LH was found. Moreover T and FSH were correlated with age only in the normoprolactinemic patients. These data suggest: a common damaging mechanism by uremia on both interstitial and tubular structures of the testis; a central antigonadal influence of hyperprolactinemia even if a direct action on the testis cannot be excluded; a worsening action of age on the gonadal function of these patients.

Relationship between plasma levels of factor VIII related antigen and reticulo-endothelial function in chronic uremia.

The plasma levels of factor VIII related antigen (F VIIIR:Ag; determined by rocket electrophoresis) and reticulo-endothelial function (measured by means of the removal kinetics of human albumin millimicrospheres) were studied in a group of patients with chronic renal failure. F VIIIR:Ag plasma levels were increased, median 304% (interquartile ranges 211-443%) compared to the controls, median 112% (interquartile ranges 100-144%); P less than 0.01. Reticulo-endothelial function was decreased, median 8.3 micrograms/min/kg body wt (interquartile ranges 6.2-10.1 micrograms/min/kg body wt) compared to the controls, median 15.0 micrograms/min/kg body wt (interquartile ranges 11.9-19.0 micrograms/min/kg body wt); P less than 0.02. A significant inverse relationship was found between plasma levels of F VIIIR:Ag and the reticulo-endothelial function rs = 0.075; P less than 0.01). As the main site of catabolism of F VIIIR:Ag is the reticulo-endothelial system, the impairment of its function appears to be a possible explanation for the elevated plasma levels of the F VIIIR:Ag found in patients with end stage renal disease.

Carnitine deficiency induced during hemodialysis and hyperlipidemia: effect of replacement therapy.

Plasma carnitine levels were studied in 14 uremic patients before, during, and after hemodialysis. The predialysis plasma carnitine levels were normal but fell during dialysis (half-life of 3.6 h). Plasma carnitine levels rose quickly in the first 6 h after dialysis, after which time the rise was more gradual. Muscle carnitine was significantly reduced in the dialyzed patients (p less than 0.005) compared with controls. In four patients lipid droplets were observed in muscle. Ten patients on maintenance hemodialysis exhibited plasma hyperlipidemia and low muscle carnitine. These individuals were given DL-carnitine (50 mg/kg body weight) intravenously after each dialysis. At the end of a 2-month carnitine treatment, plasma triglyceride levels were found to be reduced (p less than 0.001) and muscle carnitine content significantly increased (p less than 0.005). These findings suggest that carnitine may be useful in treatment of hypertriglyceridemia and muscle carnitine deficiency states induced during maintenance hemodialysis.