Interferon treatment for patients with chronic hepatitis C complicated with chronic renal failure receiving hemodialysis.

BACKGROUND AND AIMS: The Japan Society for Dialysis Therapy established "Guidelines for the Treatment of Hepatitis C Virus Infection in Dialysis Patients." We evaluated the status of HCV infection and the treatment of hemodialysis patients in Gunma prefecture. METHODS: Questionnaires concerning the infection rate, recognition of the guidelines, and treatment status were sent to all 64 hospitals/clinics that had hemodialysis systems in Gunma prefecture. The hepatitis C virus-infected hemodialysis patients who received pegylated interferon (peg-IFN) were analyzed at Gunma University Hospital. RESULTS: The positive rate for hepatitis C virus antibody was 256/2582 hemodialysis patients (9.9%). The positive rate varied between institutions (range 0-40.0%; median 9.0%). All institutes recognized the establishment of the guidelines. Conventional or peg-IFN treatment was being given at 37.5% of the institutions. The other 62.5% institutions answered that they intended to provide the treatment in the future if collaboration with a hepatologist could be arranged. The most common answers regarding the indication for IFN treatment were as follows: few complications, under 60 years of age, more than 10 years of survival expected on hemodialysis. Eighteen patients received peg-IFN treatment. The sustained virological response rate of all patients was 33.3%, 0% in 1b/high viral titer, 50% in genotype 2, and 100% in genotype 2/low viral titer. The sustained virological response rate was worse in the patients with 1b/high viral load and diabetic nephropathy (P < 0.05). CONCLUSIONS: Recognition of the publication of the guidelines was high. However, the number of patients treated with peg-IFN was still low. Further enlightenment and cooperation between hemodialysis teams and hepatologists are therefore needed.

Impact of brachial-ankle pulse wave velocity and ankle-brachial blood pressure index on mortality in hemodialysis patients.

BACKGROUND: Pulse wave velocity (PWV) and ankle-brachial blood pressure index (ABPI) are markers for atherosclerosis, and each predicts mortality in patients undergoing hemodialysis. However, there have been no studies in the past that compared head-to-head the clinical validity of these 2 parameters. Compared with conventional aortic PWV, brachial-ankle PWV (baPWV) is considered simple and thereby easily applicable to clinical use. METHODS: To clarify the relationship between baPWV and ABPI and assess their prognostic values, we analyzed 785 hemodialysis patients with a mean age of 60.2 +/- 12.5 (SD) years for whom ABPI and baPWV at baseline had been measured simultaneously and who were followed up for 33.8 +/- 10.8 months. RESULTS: Of 785 patients, 131 deaths were recorded. In Kaplan-Meier analysis, all-cause mortality was progressively and significantly greater from the lowest quartile of baPWV onward (log-rank test, 41.8; P < 0.001). However, in Cox proportional hazards analysis, the impact of baPWV was insignificant when ABPI was included as a covariate. ABPI maintained strong predictive power in this model. When patients who had advanced peripheral arterial occlusive disease (ABPI < 0.9) were excluded from analysis, patients with the highest quartile of baPWV had significantly increased hazard ratios of all-cause (hazard ratio, 4.08; 95% confidence interval, 1.46 to 11.43; P < 0.007) and cardiovascular (hazard ratio, 7.03; 95% confidence interval, 1.49 to 33.08; P < 0.014) mortality. The predictive power of baPWV in this population was independent from other covariates associated with atherosclerotic disorders. CONCLUSION: In a head-to-head comparison, ABPI, but not baPWV, showed strong power in predicting the mortality of hemodialysis patients. However, baPWV was useful to pick a high-risk population in patients with ABPI greater than 0.9. Thus, screening hemodialysis patients by means of baPWV and ABPI provides complementary information in identifying a high-risk population.

Secretion of parathyroid hormone oscillates depending on the change in serum ionized calcium during hemodialysis and may affect bone metabolism.

BACKGROUND: The current study was undertaken to clarify the dynamic response of parathyroid hormone (PTH) during hemodialysis and to determine whether or not such dynamic change of PTH affects bone turnover. METHODS: Serum ionized calcium (iCa) and intact PTH (iPTH) were measured in 66 dialysis patients before (basal) and after each hemodialysis. The changes of iCa (DeltaiCa) and iPTH (DeltaiPTH) were defined as [postdialysis iCa -basal iCa] mM, and [(postdialysis iPTH - basal iPTH)/basal iPTH] x 100%, respectively. We also investigated the data of the patients divided into four groups based on their basal iPTH levels; group 1 (iPTH < 60 pg/ml, n = 17), 2 (> or = 60 to < 150, n = 20), 3 (> or = 150 to < 300, n = 15), and 4 (> or = 300, n = 14). RESULTS: While iCa and iPTH changed variably during each hemodialysis procedure, there was a highly significant inverse correlation between DeltaiCa and DeltaiPTH (r = -0.761, p < 0.0001). Regression coefficients between DeltaiPTH and DeltaiCa were -519.1, -311.2, -268.1, and -194.6%/mM in groups 1-4, respectively. The difference in the regression coefficient was statistically significant between group 1 and 2 (F = 3.69, p < 0.05, ANCOVA), group 1 and 3 (F = 5.599, p < 0.05), and group 1 and 4 (F = 10.853, p < 0.005). This suggested that patients with higher basal iPTH responded poorly to modulate serum PTH levels by sensing the change of iCa. However, after an intensified oral calcitriol therapy to reduce iPTH, the PTH response in group 4 patients was restored to levels comparable with those observed in patients having lower basal iPTH. We also demonstrate that the DeltaiPTH of patients of group 1 but not of other groups was significantly correlated with serum markers for bone metabolism; osteocalcin (r = 0.535, p < 0.05) and collagen type I C-terminal telopeptide (r = -0.575, p < 0.05). CONCLUSIONS: Our findings suggest that secretion of PTH is dynamically regulated by DeltaiCa during hemodialysis and such oscillated PTH secretion may affect bone metabolism in a subset of dialysis patients.

Mesangial cells stimulate differentiation of endothelial cells to form capillary-like networks in a three-dimensional culture system.

BACKGROUND: There are conflicting results regarding the role of periendothelial mural cells in angiogenesis. In the current study, we investigated the role of mesangial cells (MCs) in endothelial vascularization by using a three-dimensional co-culture system in basement-membrane reconstruct gel (Matrigel). METHODS: Human umbilical vein endothelial cells (ECs) and human MCs were used. In the contact co-culture system, ECs and MCs were mixed and then plated together onto Matrigel. In the non-contact co-culture system, MCs were cultured within an intercup chamber, which prevented direct physical contact with the ECs on the Matrigel but allowed both cell types to share culture medium. To visualize ECs and MCs, the cells were labelled with two different fluorescent dyes prior to the co-culture. A capillary-like network formation was observed under a fluorescent microscope and confocal microscope, and the length of the network formation was quantified by the image analyzer. RESULTS: ECs barely formed capillary-like networks when cultured alone in growth factor-free medium. However, ECs cultured with MCs in a contact condition remarkably formed capillary-like networks (9.10+/-0.96 vs 0.20+/-0.07 mm/mm2 at 6 h, contact vs ECs alone, P<0.001). Direct contact between ECs and MCs was clearly demonstrated by confocal microscopy. Differentiation into branching capillary-like structures was also observed in the non-contact co-culture system (3.02+/-1.21 mm/mm2 at 6 h, P<0.001 vs ECs alone), but less prominently than in the contact co-culture condition. Vascular endothelial growth factor (VEGF) was secreted from MCs, as determined by enzyme-linked immunosorbent assay and immunofluorescent study. Adding neutralizing antibodies against VEGF into the co-culture system partially inhibited capillary network formation. CONCLUSIONS: Our data indicate that MCs help ECs differentiate toward vascularization, in which the direct cell-cell contact between ECs and MCs plays an important role. VEGF is a mediator in this process.