Kinetics of hepatitis B virus load and haemodialysis: a prospective study.

The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been an important goal in the management of patients on regular dialysis but infected patients continue to enter the dialysis system. It is evident that HBV viraemia in hepatitis B surface antigen (HBsAg)-positive patients on dialysis is low but it remains unclear whether haemodialysis per se can contribute to viral load reduction in such patients. HBV DNA was determined in 40 HBsAg-positive patients on maintenance haemodialysis immediately before and at the end of a 4-h haemodialysis session. The same measurements were repeated 48 and 72 h later. Twenty (50%) of 40 HBsAg-positive patients had detectable HBV DNA in serum. Detectable HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in the majority of patients after haemodialysis, although the difference was not significant (29 390 +/- 48 820 vs 23 862.8 +/- 4 350 copies/mL, NS). There was a strong relationship between mean HBV DNA levels before dialysis and absolute reduction of HBV DNA during haemodialysis sessions (r = 0.75, P = 0.0001). No difference occurred in the magnitude of change in HBV DNA titre when comparing cellulosic to synthetic membranes. Haemodialysis per se leads to a reduction in HBV load in HBsAg-chronic carriers on maintenance dialysis. This phenomenon could explain the low viral loads in these patients. Prospective studies are in progress to identify the mechanisms responsible for reduction in HBV load during haemodialysis.

Effects of porcine calcitonin on human platelet fuction.

The effects of different doses of porcine calcitonin (pCT) were tested in vitro and in vivo. In vitro, pCT at a concentration ranging from 0.1 to 5 M. R. C. Units/ml induced a dose-dependent inhibition of ADP (1.2 microM) and collagen- (2 micrograms/ml) induced platelet aggregation, showing a prevalent action on the second wave of ADP-induced aggregation and causing prolongation of the lag time and reduction of both maximum aggregation and slope in collagen-induced aggregation. 45Ca uptake by platelets in the presence of the ionophore A23187 and 14C-serotonin release were also inhibited in a dose-related fashion, using concentrations ranging from 1 to 10 M. R. C. Units of pCT. The in vivo tests, performed before and after a 7-day treatment with 2 different doses of pCT (1 and 160 M. R. C. Units/daily, i. m.) confirmed the inhibitory effect of pCT on ADP- and collagen-induced platelet aggregation. It should be stressed that the effect of 1 unit was stronger than that of 160 units. It is therefore postulated that in vitro and in vivo effects of pCT on platelet functions probably depend on different mechanisms of action.

Basal plasma levels of calcitonin and bone mineral mass in normal and uremic women. Effect of menopause.

Basal plasma levels of immunoreactive calcitonin (iCT), forearm bone mineral content (BMC) as measured by 125I photon absorptiometry and 24-hour urinary hydroxyproline/creatinine ratio (OHPr/Cr) were determined in 32 healthy women (13 pre-menopausal, aged 40 to 54 years, and 19 post-menopausal, aged 41 to 54 years). The basal plasma levels of iCT were significantly higher in the pre-menopausal group (mean value 96 vs 54 pg/ml, P less than 0.025). The BMC value of the radius was also significantly greater in the same group (mean +/- SEM 656 +/- 13 vs. 620 +/- 9 mg/cm2, P less than 0.05), while the urinary OHPr/Cr ratio was higher in the post-menopausal group (29.9 +/- 1.5 vs. 38.7 +/- 2.7 mg/g, P less than 0.02). These results suggest that basal plasma levels of iCT decrease after the menopause and support the hypothesis that a deficiency of CT could be involved in the pathogenesis of post-menopausal bone loss. Similar results were obtained in 25 uremic women on maintenance hemodialysis (9 pre-menopausal and 16 post-menopausal) aged 30 to 65 yrs.: both basal iCT levels and BMC values were significantly higher in the pre-menopausal group.

Calcium metabolism in multiple myeloma.

45Calcium metabolism and circulating levels of iPTH (N-terminal fragment) and iCT were investigated in normocalcemic patients with multiple myeloma (12) in an attempt to ascertain early changes in calcium metabolism, which may occur before hypercalcemia develops. The same parameters were also investigated in patients with senile osteoporosis (11), corticosteroid-induced osteoporosis (6), Paget's disease (6) and controls without bone disorders (13). In the myeloma group, the exchangeable calcium pool (7,678 +/- 321 mg) was significantly higher (P less than 0.01) than in the control group (4,405 +/- 374 mg), the senile osteoporosis group (4,108 +/- 407 mg) and the corticosteroid-induced osteoporosis group (3,015 +/- 161 mg) and nearly as high as in the Paget's disease group (8,876 +/- 1,173 mg). Calcium pool turnover rate was higher in the myeloma group than in controls, as were bone anabolism and bone catabolism, although differences were not statistically significant. There were no statistically significant differences among the groups in the plasma iPTH or iCT, although the mean value of the latter was higher in the myeloma group than in controls (86 +/- 24 vs. 47 +/- 13 pg/ml). These data suggest that an increase in the exchangeable calcium pool and in turnover rate may occur early in the course of multiple myeloma, preceding the development of hypercalcemia. The role of some homeostatic mechanisms in maintaining normal plasma calcium levels in multiple myeloma despite increased bone calcium resorption is discussed.

[Intravenous folinic acid and vitamin B12 supplementation and homocysteine concentration in hemodialysis patients]. / Supplementazione e.v. di acido folinico e vitamina B12 e concentrazioni di omocisteina nei pazienti emodializzati.

INTRODUCTION: Hyperhomocysteinemia is one of the causes of the increased incidence of cardiovascular disease in uremia. Since homocysteine (Hcy) metabolism depends on the availability of folate and vitamin B12, we have measured the effects of chronic i.v. supplementation of folinic acid and vitamin B12 in a group of patients on maintenance hemodialysis. METHODS: We compared the blood concentration of total Hcy (tHcy), vitamin B12 and folate and the intraerythrocyte concentration of folate in a group of 27 hemodialysis patients (Treated group), given an i.v supplementation with folinic acid (0.9 mg) and Vitamin B12 (cyanocobalamine 1.5 mg and hydroxycobalamine 1.5 mg) three times per week at the end of each dialysis session with those measured in a similar group of 28 hemodialysis patients without supplementation (No Treatment group). The patients were also characterized for the thermolabile variant (mutation C667-->T) of the enzyme methylene-tetrahydrofolate reductase (tMTHFR). RESULTS: High plasma levels (< 11.7 micromol/L) of tHcy were observed in 54/55 patients. T patients had Hcy values significantly lower than NT ones (31.7+/-3.6 vs. 1.1+/-8.3micromol/L, p < 0.05). Serum vitamin B12 (1200 73.6 vs. 762+/-72.2 pmol/L, p < 0.001) and intraerythrocyte folate levels were also significantly higher in the T group (2176+/-127 vs. 1511+/-156, p < 0.005), while no significant difference was observed for serum folate. The distribution of tMTHFR genotypes was similar in the two groups. Homozygous patients showed higher levels of Hcy in comparison with wild type patients both in the whole population (62.32+/-15.9 vs.30.43+/-3.2, p < 0.05) and in the NT group (87.8+/-25.3 vs.36.8+/-13.1., p < 0.05), while no significant difference was observed among genotypes in the T group. CONCLUSIONS: Uremic patients on hemodialysis, when supplemented with even low i.v. dose of folinic acid and vitamin B12, show significantly lower plasma levels of tHcy than non-supplemented patients.

Increased forearm bone mineral content after bromocriptine treatment in hyperprolactinemia.

We studied 15 hyperprolactinemic women to evaluate possible modifications of bone mineral content after pharmacological treatment. Patients received a dopamine agonist (bromocriptine) for six months after which there was a significant decrease of prolactin plasma levels (P less than 0.01) and a significant increase of bone mineral content (P less than 0.05).

Bone involvement in primary hemochromatosis and alcoholic cirrhosis.

Biochemical indexes of bone metabolism, bone mineral density, and histomorphometry were evaluated in 14 male patients with noncholestatic cirrhosis due to primary hemochromatosis (six cases) or to chronic alcohol abuse (eight cases), and in 30 male controls of similar age. Alkaline phosphatase in alcoholic patients was significantly higher than in controls (mean +/- SD 50.4 +/- 33.7 vs 33.0 +/- 7.1 U/L, p less than 0.01), as was urinary hydroxyproline in both hemochromatotics and alcoholics (mean +/- SD, 44.3 +/- 8.4 and 40.4 +/- 16.8, respectively, vs 30.1 +/- 4.5 mg/g, p less than 0.001 and p less than 0.005). Bone mineral density was significantly lower in hemochromatotics than in alcoholics and controls (mean +/- SD, 591 +/- 90 vs 765 +/- 87 and 759 +/- 34 mg/cm2, respectively, p less than 0.005 and p less than 0.001). At bone biopsy, trabecular osteoporosis was observed in two hemochromatotics and four alcoholics, and osteomalacia was seen in another alcoholic. Overall densitometric and histomorphometric findings indicate a derangement of trabecular bone in both alcoholic and hemochromatotic cirrhosis, whereas cortical osteoporosis seems limited to hemochromatotic patients.

Nonacidotic kidney proximal tubulopathy with absorptive hypercalciuria.

We studied three patients with proximal tubulopathy characterized by defective reabsorption of phosphate, glucose, amino acids, urate, and low molecular weight proteins. This tubulopathy differs from Fanconi syndrome in that the patients had normal plasma bicarbonate and absorptive hypercalciuria associated with increased 1,25-dihydroxyvitamin D levels. The youngest patient was rachitic and may be classified with previously described patients, whereas the other two patients presented with nonrachitic osteopenic bone disease and their tubulopathy started during adult life. Kidney defects appeared sequentially in one of the nonrachitic patients. The two brothers of the youngest patient had similar kidney and bone disturbances. One of the other two patients had a brother with similar kidney reabsorption defects; an additional brother was probably affected and a sister presented with glycosuria, but no other reabsorption defects. The findings in these two families suggest a genetic transmission of proximal tubulopathy. The third case was sporadic. Renal histology of the three patients showed a great number of giant cells in the tubular lumen. We conclude that, at least in our adult patients, tubulopathy may represent a new entity among the proximal tubular dysfunction cases described to date. The features of this proximal defect suggest that it may be caused by a selective alteration of luminal cell membrane transport of phosphate, glucose, amino acids, urate, and proteins in the presence of a normal sodium gradient across the tubular cell membrane.

Reduction of the homocysteine plasma concentration by intravenously administered folinic acid and vitamin B(12) in uraemic patients on maintenance haemodialysis.

BACKGROUND: Hyperhomocysteinaemia is an independent cardiovascular risk factor which can induce vascular lesions, thus contributing to the early development of atherosclerosis. Low-dose folic acid supplementation reduces the pretreatment homocysteine plasma levels by 25-35%. Recent studies report that higher intravenous or oral administration of the active form of folic acid reduces the homocysteine plasma concentration by nearly 70%. The reduction could also be influenced by the thermolabile variant of methylenetetrahydrofolate reductase (tMTHFR) and by the dialysis modality. METHODS: A cross-sectional clinical study was performed to evaluate the effect of a drug containing folinic acid and vitamin B(12) on the plasma homocysteine concentration and whether this variable could also be influenced by the presence of a genetic variant of the methionine pathway and the use of different dialysis modalities. The plasma homocysteine concentration was measured in 55 patients undergoing haemodialysis, 27 of whom have been treated intravenously for megaloblastic anaemia using a drug containing low concentrations of folinic acid and vitamin B(12) at the end of each dialysis session for 6 months. The presence of tMTHFR was sought by molecular analysis, and the role of the dialysis modality was also investigated. RESULTS: The patients given the folic acid treatment had lower homocysteine plasma levels than those not so treated. The plasma homocysteine concentration was significantly higher in the tMRHFR homozygotes than in the patients with a normal genotype, significantly lower in the treated than in the untreated homozygotes, and significantly higher in the untreated homozygotes than in the untreated subgroup with a normal genotype. The homocysteine level was also significantly lower in the patients who underwent convective haemodialysis than in those who received standard bicarbonate dialysis. CONCLUSIONS: A drug containing low concentrations of folinic acid combined with vitamin B(12) using an intermittent intravenous regimen is effective in reducing the homocysteine plasma concentration in uraemic patients. The homocysteine levels seem also to depend on genotype and dialysis modality.