Giovanna Como

Changes in viremia and circulating interferon-α during hemodialysis in hepatitis C virus-positive patients: only coincidental phenomena?

BACKGROUND It has been hypothesized that hemodialysis (HD) treatment per se can preserve patients from an aggressive course of hepatitis C virus (HCV) infection by reduction of viral load. The aim of the present study in HCV-positive (HCV+) HD patients is to determine whether HD induces the production of interferon-alpha (IFN-alpha) and if such production can contribute to viremia reduction. METHODS To address this issue, HCV RNA and IFN-alpha levels were determined in 11 HCV+ patients immediately before and at the end of a 4-hour dialysis session using cellulosic membranes and 24 and 48 hours later, ie, immediately before the subsequent dialysis session using the same membrane and at the end of the dialysis session. The same protocol was repeated 1 week later using a high-biocompatibility synthetic membrane. RESULTS HCV titer decreased in all patients after dialysis (range, 3% to 95%; P = 0.001) and thereafter progressively increased and returned to basal levels within 48 hours, with a new reduction during the next dialysis treatment. There was no significant difference in the magnitude of changes in HCV titers in tests performed using cellulosic or synthetic membranes. Plasma IFN-alpha levels increased markedly after dialysis using both cellulosic (in 9 of 11 cases) and synthetic membranes (in 10 of 11 cases; P < 0.01) and returned to basal levels within 48 hours; thereafter, IFN-alpha levels increased again during the next dialysis session. In some patients, plasma IFN-alpha levels after HD were approximately 50% of the level observed after therapeutic administration of 6 million units of IFN-alpha to 4 HD patients with chronic hepatitis. CONCLUSION Although without a proven direct cause-effect relationship between HCV level reduction and induction of IFN-alpha after dialysis, our observation suggests an additional new mechanism for the unusually mild course of HCV infection in HD patients.

Calcium and phosphate plasma levels in dialysis patients after dietary Ca-P overload: Role of gastric acid secretion

In normal subjects, the gastric ionisation of calcium and phosphate seems to be a prerequisite for their intestinal absorption. We investigated the behavior of the plasma calcium and phosphate profile in 30 patients on regular dialysis treatment in the 6 h following a meal containing 1 g of calcium and 2 g of phosphate. Moreover, to assess the role of gastric acidity, the study was repeated after 3 days on omeprazole administration, to nearly abolish gastric acid secretion. Both total plasma calcium and ionized calcium peaked after the meal (at 30 and 120 min, respectively) only in basal study, while no peak was observed after the administration of omeprazole. Surprisingly, both in basal and in the omeprazole study the levels of plasma phosphate did not increase after the test meal. In conclusion, as in normal subjects, the gastric ionization of dietary calcium promotes the intestinal absorption of calcium in uremic patients on dialysis treatment, while the acute gastric acid inhibition by omeprazole reduced the intestinal calcium transport. In contrast, with the ‘trade off’ hypothesis we did not observe any postprandial phosphate peak after the dietary load, and, in contrast with normal subjects, omeprazole administration did not influence the phosphate profile.

De novo HCV infection among dialysis patients: a prospective study by HCV core antigen ELISA assay

Background : Dialysis patients remain a high‐risk group for hepatitis C virus infection. The current diagnosis of hepatitis C virus in dialysis patients includes serological measurement of anti‐hepatitis C virus antibody; however, nucleic acid amplification technology for assessing hepatitis C virus viraemia is commonly used in other populations. An enzyme‐linked immunosorbent assay test for detecting antibody to hepatitis C nucleocapsid core antigen (hepatitis C virus core antigen) in human serum has been recently developed (hepatitis C virus Core Antigen enzyme‐linked immunosorbent assay test). It is conceived for screening of donor blood products to significantly reduce the ‘serologic window’ occurring before seroconversion during acute hepatitis C virus.

High Prevalence of Silent Gallstone Disease in Dialysis Patients

Gallstone disease was detected in 28% of 119 patients on regular dialysis treatment. The disease was silent in 82% of the patients. Stones were radiolucent in 88% of the cases, radioopaque in 8% and mixed in 4%. Among 49 variables considered, increasing age was the only variable that correlated significantly with increasing prevalence of gallstone disease. Since no relationships were found between gallstones and age or modes of dialysis, it is conceivable that some mechanism(s) linked with the preexisting chronic nephropathy might have been involved in the development of cholelithiasis. End-stage renal disease could be another so far unrecognized risk factor for cholelithiasis.

Folate measurements in patients on regular hemodialysis treatment.

Patients on regular hemodialysis treatment may develop megaloblastic anemia caused by folate deficiency, but whether folate supplementation is required is still controversial, particularly during erythropoietin administration. Erythrocyte folate concentration is a better indicator of folate status than serum folate, although the latter is the variable generally measured. We measured serum and erythrocyte folate in blood samples from 112 regular hemodialysis patients (57 men, 55 women, 50 treated with erythropoietin, and 62 not) by Stratus Folate immunoenzymatic assay (Dade). Patients with very low serum (<2.87 ng/mL) but normal erythrocyte folate were reinvestigated 4 months later without receiving folate supplementation meanwhile. Serum folate concentrations were 0.48 to 12.76 ng/mL (median, 3.40) and erythrocyte folate 0.19 to 1.85 microg/mL (median, 0.42). Only 37% serum folate values were in the relevant reference interval compared with 80.2% erythrocyte folate values (3.08 to 17.65 ng/mL and 0.24 to 0.64 microg/mL, respectively). A significant correlation was found between serum and erythrocyte folate concentrations, without clinical relevance caused by the wide scatter around the regression line. Serum and erythrocyte folate did not vary significantly between patients given erythropoietin and those not so treated. The folate status of the 24 patients with very low serum folate was almost unchanged 4 months later. According to the serum folate test, 63% of patients needed folate supplementation, whereas the erythrocyte folate test, a better indicator of folate status, suggested that only 1.8% of patients needed folate supplementation. Erythropoietin therapy appears not to be an indication for standard folate supplementation in hemodialysis patients.

HFE Gene Mutations and Oxidative Stress Influence Serum Ferritin, Associated with Vascular Damage, in Hemodialysis Patients

Background/Aims: Hyperferritinemia has been associated with cardiovascular mortality in hemodialysis patients. The aim of this study was to evaluate whether serum ferritin was affected by iron and oxidative status and by genetic factors (HFE mutations and the Ala9Val MnSOD polymorphism), and to assess the association between ferritin and cardiovascular damage evaluated by ecocolor-Doppler. Methods: 63 hemodialysis patients were tested for HFE and MnSOD genotype by restriction analysis and oxidative status; vascular damage was assessed by measuring intima-media thickness, and by detecting plaques at carotid and femoral arteries. Results: Ferritin was correlated with transferrin saturation (p = 0.003), decreased iron-specific serum antioxidant activity (p = 0.01), age (p = 0.03), and C282Y and H63D HFE mutations (p = 0.05), but not with the MnSOD polymorphism. Ferritin was associated with advanced vascular damage, as evaluated by the presence of plaques, both at carotid (p = 0.03) and femoral arteries (p = 0.001), the other risk factors being age and low albumin. Low iron-specific antioxidant activity was associated with carotid plaques (p = 0.03). Conclusion: In hemodialysis patients, hyperferritinemia reflects a relative increase in iron availability and a decrease in iron-specific antioxidant activity, is favored by HFE mutations, and represents a risk factor for advanced cardiovascular damage.

HFE Genotype Influences Erythropoiesis Support Requirement in Hemodialysis Patients: A Prospective Study

Background/Aims: HFE protein controls iron absorption and cycling, and HFE mutations influence iron status. The aim was to evaluate the effect of the HFE genotype on the need for iron and erythropoietin in Italian hemodialysis patients. Methods: Ninety-six prevalent patients were evaluated at the time of enrolment and prospectively followed for 3 years. Patients were given r-HuEPO and Fe3+-gluconate according to guidelines. The HFE genotype was determined by restriction analysis. Results: Three patients (3%) carried the C282Y mutation, 4 (4%) were homozygous and 18 (19%) heterozygous for the H63D mutation, and 71 (74%) were negative for both. At enrolment, subjects positive for HFE mutations had higher iron stores (ferritin 617 ± 663 vs. 423 ± 386 ng/ml, p = 0.05), were receiving less iron (82.5 ± 66 vs. 110 ± 154 mg/month, p = 0.05) and a lower r-HuEPO dosage (98 ± 83 vs. 142 ± 138 U/kg/week, p = 0.03). Consistently during the study period, patients positive for HFE mutations received a lower amount of r-HuEPO (94.5 ± 63 vs. 186 ± 344 U/kg/week, p = 0.01) and iron (97 ± 63 vs. 121 ± 68 mg/month, p = 0.07). Upon Cox regression analysis, after adjustment for confounding variables, the presence of HFE mutations was associated with a reduced risk of death (HR 0.6, 95% CI 0.34–1.03, p = 0.06). Conclusion:HFE mutations reduce the amount of r-HuEPO and iron necessary to support erythropoiesis in hemodialysis.