Cost-effectiveness analysis of on-line hemodiafiltration in Japan.

BACKGROUND/AIMS: Evaluation of the socioeconomic value of medical intervention and establishment of the resources necessary for clinical practice are important for new developments in medical technology. The aim of this study was to determine the socioeconomic value of on-line hemodiafiltration (HDF). METHODS: The subjects were 24 patients who underwent hemodialysis (HD) (9 HDF, 15 HD) for chronic renal failure. A total of 288 dialysis interventions were observed for 4 weeks in three clinics. Cost-effectiveness was evaluated based on quality-adjusted life years (Qaly) and a visual analog scale. RESULTS: EuroQOL-5D (0.776 ± 0.015) and visual analog scale (67.9 ± 1.2) in the HDF group were higher than those in the HD group at baseline. The incremental cost utility ratio for HDF was 641.7 (JPY 10,000/Qaly) based on Qaly (0.776 ± 0.015) and reimbursement for medical fees (JPY 4,982,736 ± 7,852), and was lower than the incremental cost utility ratio for HD. CONCLUSION: These results suggest that on-line HDF could be cost-effective.

Elevated serum interleukin-18 levels might reflect the high risk of hospitalization in patients on peritoneal dialysis.

BACKGROUND: Interleukin (IL)-18 is a potent pro-inflammatory cytokine and plays a central role in atherosclerotic plaque rupture and accelerates atherosclerosis. AIM: The aim of this study was to determine serum IL-18 levels in patients on peritoneal dialysis (PD) and to assess their relationship with hospitalization. METHODS: Forty-three PD patients and 20 healthy individuals were enrolled in this study. We investigated the relationship of the serum concentrations of IL-18 and other well-established atherosclerotic markers, such as asymmetric dimethylarginine (ADMA). Hospitalization data from over a 18-month period were prospectively obtained on all 43 PD patients. Classic factors were entered into a Cox regression model to predict first hospitalization. RESULTS: The serum levels of IL-18 in patients on PD were significantly higher than those of healthy individuals (228.5 +/- 140.3 pg/mL vs 154.8 +/- 44.7 pg/mL, P < 0.05, respectively). Furthermore, serum IL-18 levels showed a positive correlation with duration of PD, serum beta2 microglobulin and serum ADMA levels. Mean serum levels of IL-18 were significantly higher among patients who had experienced at least one hospitalization than those who had not (279.9 +/- 164.3 vs 158.5 +/- 43.9 pg/mL, P = 0.0426). Furthermore, the relative risk for first hospitalization for each increase in IL-18 (pg/mL) levels was associated with a 1.182 (95% confidence interval, 1.012-1.364; P = 0.0071) increase in the risk for future hospitalization events. CONCLUSION: The present study suggests the elevated serum IL-18 levels might increase the risk for future hospitalization in patients on PD.

The critical role of SRC homology domain 2-containing tyrosine phosphatase-1 in recombinant human erythropoietin hyporesponsive anemia in chronic hemodialysis patients.

The molecular mechanism of anemia that is hyporesponsive to recombinant human erythropoietin (rHuEPO) in hemodialysis patients without underlying causative factors has not been investigated fully in hematopoietic stem cell system. Circulating CD34+ cells (1 x 10(4)) were isolated from rHuEPO hyporesponsive hemodialysis patients (EPO-H; n = 9), patients who were responsive to rHuEPO (EPO-R; n = 9), and healthy control subjects (n = 9). The patients with known causes of EPO hyporesponsiveness were eliminated from the current study. The cells were cultured in STEM PRO 34 liquid medium, supplemented with rHuEPO, IL-3, stem cell factor, and granulocyte-macrophage colony stimulating factor for 7 d and then transferred to a semisolid methylcellulose culture medium for performing burst forming unit-erythroid (BFU-E) colony assay. Expression of src homology domain 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 5 (p-STAT5) was assessed with Western blot analysis. In EPO-H patients, SHP-1 antisense or scrambled S-oligos were included in the culture medium, and its effects were evaluated. The number of circulating CD34+ cells was not statistically different among the three groups, and their proliferation rates were similar for 7 d in culture. However, BFU-E colonies were significantly decreased in EPO-H patients compared with EPO-R and control groups. The mRNA and protein expression of SHP-1 and p-SHP-1 was significantly increased, whereas that of p-STAT5 was reduced in EPO-H patients. The inclusion of SHP-1 antisense S-oligo in culture suppressed SHP-1 protein expression associated with p-STAT5 upregulation, increase in p-STAT5-regulated genes, and partial recovery of BFU-E colonies. In EPO-H hemodialysis patients, the EPO signaling pathway is attenuated as a result of dephosphorylation of STAT5 via upregulation of SHP-1 phosphatase activity, and SHP-1 may be a novel target molecule to sensitize EPO action in these patients.

Perturbation of autocrine/paracrine loops of burst-forming units of erythroid-derived cells in rHuEPO-hyporesponsive hemodialysis patients.

BACKGROUND: Quantitative or qualitative abnormalities of erythroid progenitors in patients with chronic renal failure (CRF) could be the major factor for recombinant human erythropoietin (rHuEPO) hyporesponsiveness and severe anemia in hemodialysis (HD) patients receiving rHuEPO therapy. METHODS: Purified 1 x 10(4) circulating CD34+ cells isolated from rHuEPO-hyporesponsive HD patients (EPO-H; n = 10), rHuEPO-responsive non-HD patients with CRF (EPO-R; n = 8), nonanemic HD patients without rHuEPO therapy (EPO-W/O; n = 10), and healthy volunteer controls (CON; n = 10) were subjected to a methylcellulose culture system supplemented with rHuEPO, recombinant human interleukin-3 (IL-3), recombinant human stem cell factor (SCF), and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for 14 days. RESULTS: The average number of burst-forming units of erythroids (BFU-Es) was significantly less in the EPO-H group compared with the CON and EPO-W/O groups. Furthermore, colony size also was significantly smaller in the EPO-H group. Total RNAs were extracted from approximately 100 colonies/patient and subjected to complementary DNA expression array studies of 268 growth factors, cytokines, chemokines, and their receptors. A characteristic cluster upregulated in the EPO-R and EPO-W/O groups and downregulated in the EPO-H group was identified that contained various cytokines and growth factors, including IL-6, GM-CSF, vascular endothelial growth factor B, IL-9, IL-3, leukemia inhibitory factor, and interferon alpha-2, and such receptors as thrombopoietin receptor, IL-9 receptor, and colony-stimulating factor 1 receptor. CONCLUSION: These data suggest that the cross-talk network or autocrine/paracrine regulatory loop is critically impaired in BFU-E-derived cells in EPO-H patients, and investigation of these cluster genes would facilitate the development of novel therapeutic strategies for such patients.

Significance of 8-hydroxy-2'-deoxyguanosine levels in patients with chronic renal failure.

The aim of this study was to determine the significance of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is known as a marker of oxidative stress in vivo, in patients with chronic renal failure (CRF). Fifty-one non-dialysed CRF patients (29 men and 22 women; mean +/- SD age, 57.8 +/- 12.8 years) who were under dietary therapy for at least 6 months were enrolled in the study. Both serum and urinary 8-OHdG levels were measured by using high-sensitive enzyme-linked immunosorbent assay (ELISA) kits. We examined the relationship between 8-OHdG levels and clinical indices in patients with CRF. As a result, the serum 8-OHdG level was strongly correlated with serum levels of urea nitrogen (UN; r = 0.58; P < 0.0001), creatinine (Cr; r = 0.53; P < 0.0001), and beta2-microglobulin (beta2-MG; r = 0.54; P < 0.0001). Furthermore, the serum 8-OHdG level was inversely correlated with creatinine clearance (Ccr; r = -0.54; P < 0.0001). In contrast, urinary 8-OHdG level was not correlated with any of the clinical parameters. This is the first report of 8-OHdG level determination in patients with CRF. It is suggested that serum 8-OHdG level is not sufficient as a marker of oxidative damage in patients with CRF, and it should be corrected according to the residual renal function to estimate the accurate degree of oxidative stress.

Plasma neuropeptide Y concentrations in patients on hemodialysis.

BACKGROUND: Neuropeptide Y (NPY) is a 36-amino-acid peptide that was originally isolated from the porcine brain. NPY, in contrast to leptin, is one of the most potent appetite stimulants. In some previous studies, NPY was found to be correlated with mean blood pressure (MBP) and fluid volume in patients on hemodialysis (HD), contributing to volume-induced hypertension. However, it is still unclear which NPY-sensitive neuronal pathways are responsible for the various changes seen in response to central NPY administration. In this study we analyzed the correlation of circulating levels of NPY with parameters of nutritional conditions, and we investigated the relationships between NPY concentrations and clinical markers of fluid volume in patients on HD. We also evaluated the effects of high-flux dialysis membranes on plasma NPY levels as compared with those of low-flux membrane. METHODS: Plasma NPY concentrations in patients on regular HD were measured using commercially available radioimmunoassay (RIA) kits. We examined the relationship between plasma NPY concentration and other clinical indices in patients on HD. RESULTS: Plasma NPY concentrations were inversely correlated with the serum urea nitrogen levels (r = -0.32) as well as protein catabolic rate (PCR) (r = -0.28). Plasma NPY was also correlated with the increase in body weight between HD sessions (r = 0.29). On the other hand, plasma NPY concentrations were not correlated with MBP, atrial natriuretic peptide (ANP), or adrenomedullin (AM). The reduction rate of plasma NPY with a high-flux dialysis membrane was significantly higher than that with a low-flux dialysis membrane. CONCLUSIONS: The secretion of NPY may be enhanced in a poor state of nourishment and stress induced by fluid volume overload in patients on HD, and plasma NPY is removed by a high-flux dialyzer.

[A case of minimal change nephrotic syndrome manifesting acute renal failure in the course of systemic lupus erythematosus].

A 51-year-old woman with systematic lupus erythematosus(SLE) associated with minimal change nephrotic syndrome(MCNS) is described. The patient was diagnosed as SLE at 33 years of age. After steroid therapy for two years, the patient's course was uneventful without therapy until June 2000, when facial erythema and facial, pretibial edema developed. On admission, proteinuria and renal dysfunction were detected. Subsequently, oliguric acute renal failure developed and hemodialysis was started. Laboratory examination showed no significant change in complements and anti ds-DNA antibody levels. Renal biopsy revealed minor glomerular abnormalities without the deposition of immune complexes. Electron microscopic examination showed foot process fusion and a vacuolar change in glomerular epithelial cells. The diagnosis of MCNS was made and administration of steroid(40 mg/day) was started. Urine volume and renal function improved after 2 weeks, and nephrotic syndrome remitted completely after 5 weeks. Although the association of SLE and MCNS is rare, the findings suggest that in the course of SLE manifesting acute ranal failure, not only lupus nephritis, but also the complication of MCNS should be considered.

Serum levels of soluble CD26 and CD30 in patients on hemodialysis.

BACKGROUND/AIMS: Various abnormalities of the immune system have been demonstrated in patients on hemodialysis (HD). We hypothesize that the imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells in patients on HD contributes to these abnormalities. Furthermore, we investigate the relationship between the Th1/Th2 imbalance and HD duration. METHODS: We measured the serum levels of soluble CD26 (sCD26) and soluble CD30 (sCD30) in 47 patients on HD and in 13 patients with chronic renal failure not on HD and analyzed the effect of HD duration on the serum levels of sCD26 and sCD30. RESULTS: The serum level of sCD26 in the HD group was significantly lower than that in the control group. On the other hand, the serum levels of sCD30 in the HD group and in the CRF group were significantly higher than in the control group. In the short-term HD group (<1 year), the serum levels of sCD26 were lower and the sCD30 levels higher than those in middle-term HD group (1-10 years). CONCLUSIONS: In the HD group, the Th1/Th2 balance may shift towards Th2 dominance. It is possible that this imbalance contributes to the abnormality of the immune system in HD patients.

Plasma orexin concentrations in patients on hemodialysis.

BACKGROUND: Orexins A and B are neuropeptides that regulate feeding behavior and are localized exclusively in neurons within and around the lateral hypothalamic area. Intracerebroventricular injection of orexin A stimulates food consumption in rats. Plasma concentrations of orexins may reflect nutritional states and may have clinical significance in patients on hemodialysis. In this study, we investigated the relationship between plasma orexin concentrations and nutritional states in patients on hemodialysis. METHOD: We measured plasma orexin concentrations in patients on hemodialysis (HD group, n = 67), patients with IgA nephropathy (n = 10), patients with diabetes mellitus (n = 11) and healthy controls (n = 10). We examined the relationships between plasma orexin concentrations and nutritional indices. RESULTS: Plasma orexin A concentrations were significantly higher in the HD group than in the control group and showed a significant correlation with serum creatinine. In all subjects, there was a positive correlation between the plasma orexin A concentration and the serum creatinine concentration, but there were no correlations between these concentrations in each group. In the HD group, plasma orexin A concentrations had a significant positive correlation with the serum albumin concentration and percent creatinine generation rate (%CGR). Multiple regression analysis demonstrated that %CGR was the only independent factor associated with plasma orexin A concentrations. CONCLUSION: Plasma orexin A concentrations are increased in patients on hemodialysis. It is possible that the kidney plays a major role in the clearance of orexins. The plasma orexin A concentration is significantly correlated with %CGR, and it may be able to be used as a clinical marker of the nutritional state in patients on hemodialysis.

Expression of Fc gamma receptor III (CD16) on monocytes during hemodialysis in patients with chronic renal failure.

BACKGROUND/AIMS: Circulating CD14+CD16+ monocytes, a potent phagocytosing and antigen-presenting monocyte population, have been reported to be expanded in patients on hemodialysis (HD). In this study, changes in the population of CD14+CD16+ monocytes were analyzed during a single session of HD therapy, and the influence of dialyzer membrane materials on these monocytes was investigated. METHODS: Nine patients were hemodialyzed using regenerated cellulose (RC) membranes and thereafter polysulfone (PS) membranes. Peripheral blood cells were taken from these subjects, and these cells were stained with anti-CD14 and anti-CD16 antibodies. The percentages of CD14- and CD16-expressing monocytes were analyzed by two-color flow cytometric analysis. Moreover, the serum soluble CD14 (sCD14) levels were measured with an ELISA kit. RESULTS: It was found that CD14+CD16+ monocytes before HD were significantly increased in patients on HD as compared to healthy controls. In the RC group, CD14+CD16+ monocytes were decreased at both 30 and 240 min after the initiation of HD. The reduction rate of CD14+CD16+ monocytes in the RC group was higher than that in the PS group. There was no significant difference in sCD14 levels between the two groups. CONCLUSION: Monocytes are activated in patients on HD. Furthermore, the population of CD14+CD16+ monocytes was stimulated to a greater extent during HD in the RC group than in the PS group. The significant reduction in CD14+CD16+ monocytes by RC membranes indicated that the level of CD14+CD16+ monocytes is a sensitive marker for the biocompatibility of HD membranes.