Abnormal glucose metabolism in uremia may result from a complex interplay between decreased insulin secretion and insulin resistance. Recent studies report beneficial effect of biotin administration in glucose metabolism in diabetic animals and in a small number of patients with diabetes mellitus. The aim of the present study was to evaluate the response of oral glucose tolerance test (OGTT) to the i.v. administration of large doses of biotin in hemodialysis patients. Eleven hemodialysis patients aged 56.90 +/- 11.20 (32-76) years on regular hemodialysis thrice a week for 2.72 +/- 1.79 (1-7) years were studied. Fasting venous plasma glucose, glucosylated hemoglobin (%GH), and plasma glucose concentration 2 h after the administration of a 75-g glucose load were measured before, and 2 weeks and 2 months after administration of 50 mg of biotin i.v. postdialysis, and after a 2-month washout period. During the study, dialysis schedule and patients' medication, diet, and dry weight were kept unchanged. OGTT was abnormal in 4 patients before biotin administration and became normal in 3 patients (75%). Our results offer support to the findings of other studies about the beneficial effect of biotin in experimental or clinical diabetes mellitus, and argue for the involvement of biotin in glucose metabolism.
It has been reported recently that a number of cytokines, mainly tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNFalpha, IL-1beta, IL-6, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre-HD) and after HD (post-HD), in one session. The post-HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNFalpha and IL-1beta levels were significantly increased from 38.24 +/- 17.85 pg/ml and 2. 60 +/- 3.64 pg/ml pre-HD to 48.86 +/- 25.21 and 3.49 +/- 4.08 pg/ml post-HD, p < 0.001 and p < 0.05 respectively. Also Lp(a) levels presented a statistically significant increase post-HD and were almost doubled (pre-HD: 15.41 mg/dl, to post-HD: 27.39 mg/dl, p < 0. 05). Serum IL-6 as well as serum TC, TG, HDL-C, and LDL-C did not show any statistically significant alterations during HD. A significant positive correlation was detected between TNFalpha and Lp(a) values post-HD (r: 0.413, p: 0.04), but not between pre-HD values. No further relationship between serum cytokines and the other estimated lipid parameters was observed, either between pre- or post-HD values. Our results indicate that release of TNFalpha and IL-1beta during HD have no effect on serum lipids concentration, except on Lp(a). It seems that the acute rise of this lipoprotein during hemodialysis may be related with the TNFalpha overproduction.
Two dynamic tests (Gn-RH i.v. and clomiphene citrate-CC p.o.) were used to evaluate the hypothalamic-pituitary axis in hemodialysis patients and renal transplant recipients (recipients). In the Gn-RH test the gonadotropin secretion was maximally decelerated in hemodialysis patients while it was normal in recipients. During the CC test a decrease of gonadotropin secretion, chronically and quantitatively identical for both group, was found; while on the following test days an increase was noted, which was more accelerated in male recipients. In cases with uremia a strong negative feedback dominates at the pituitary level probably owing to testicular inhibin. The estrogenic feedback in uremia was intact, while the antiestrogenic feedback at the level of hypothalamus is partly impaired, owing to altered opioid metabolism.
This study determines the relationship between interdialytic water retention (IWR) and acid-base homeostasis in uremic patients under regular hemodialysis (HD). To this aim, in 33 regular bicarbonate HD sessions of 11 uremic patients (three HD sessions of 1 week for each patient), blood samples were received from arterial line immediately pre- and post-HD anaerobically in heparinized syringes and the HCO3-, pH, and pco2 were determined. Also in the studied HD sessions, the IWR was estimated and the apparent bicarbonate space percentage (ABS%) pre- and post-HD was calculated by Fernandez et al. (Eq. 1). The mean +/- SD values pre-HD (ABS% = 54.15 +/- 1.49, HCO3- = 18.54 +/- 2.0 mmol/L, pH = 7.32 +/- 0.02, pco2 = 35.44 +/- 3.10 mmHg) and post-HD (ABS% = 49.88 +/- 0.6, HCO3- = 26.33 +/- 1.6 mmol/L, pH = 7.44 +/- 0.02, pco2 = 37.69 +/- 3.00 mmHg) show metabolic acidosis pre-HD and slight alkalosis post-HD. There was a significant positive correlation between IWR and ABS% pre-HD (r = 0.650, p < .0001) and post-HD (r = 0.655, p < .0001), but a significant negative correlation between IWR and HCO3- pre-HD (r = -0.502, p < .003) and post-HD (r = -0.700, p < .001), as well as between IWR and pH pre-HD (r = -0.516, p < .002) and post-HD (r = -0.377, p < .03). In addition, there was a significantly negative correlation between IWR and pco2 post-HD (r = -0.656, p < .001), but not pre-HD (r = 0.0136, PNS). The significantly positive relationship between IWR and ABS% pre- and post-HD, in combination with the significantly negative correlation between HCO3- and pH pre- and post-HD, indicates that the IWR negatively influences the acid-base homeostasis in hemodialysis patients without residual renal function, and may worsen the cardiovascular physiology and tissue oxygenation of these patients.
The safety and effectiveness of a low molecular weight heparin (LMWH) of 4500 +/- 1500 Daltons were evaluated in eight hemodialysis (HD) patients, in comparison with unfractionated heparin (UFH). In phase A of the study 3000 +/- 500 anti-factor Xa (AFXa) IU of LMWH were administered in bolus for the three consecutive HD sessions of a week. In phase B, 10000 +/- 2500 IU of UFH were administered to the same patients for the same time. Were observed no significant differences in hematocrit (Ht), platelets (Pt), fibronogen (FG) and prothrombin time (PT). Whole blood activated coagulation time (WBACT) was more prolonged with LMWH, 24 and 48 hours (start of next session) after administration (p < 0.05), and less prolonged at 5, 60, 120, 180, 240 min compared to UFH (p < 0.001). The activated partial thromboplastin time (APTT) and AFXa activity were more prolonged with UFH at 60 and 240 min (p < 0.001). The clinical effectiveness of the two preparations was similar as judged by thrombus formation and compression time. In conclusion, the present study found no real differences between LMWH and UFH, except for prolongation of WBACT 24 and 48 hours after the administration of LWMH. This probably indicates a cumulative effect of the LMWH and needs further investigation.
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