The risk of lower gastrointestinal bleeding in low-dose aspirin users.

BACKGROUND: Aspirin increases the risk of gastrointestinal bleeding. AIM: To investigate the risk of lower gastrointestinal bleeding (LGIB) in aspirin users. METHODS: Low-dose (75-325 mg daily) aspirin users and controls matched by age, gender and enrollment time in a 1:5 ratio were selected from 1 million randomly sampled subjects in the National Health Insurance Research Database of Taiwan. Cox proportional hazard regression models were developed to evaluate the predictors of LGIB with adjustments for age, gender, comorbidities including coronary artery disease, ischaemic stroke, diabetes, hypertension, chronic kidney disease, liver cirrhosis, chronic obstructive pulmonary disease, dyslipidemia, uncomplicated peptic ulcer disease, history of peptic ulcer bleeding, and concomitant use of clopidogrel, ticlopidine, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors, steroids, proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), nitrates, alendronate, selective serotonin reuptake inhibitors (SSRIs) and calcium channel blockers. RESULTS: A total of 53 805 aspirin users and 269 025 controls were included. Aspirin group had a higher incidence of LGIB within 1 year than control group (0.20% vs 0.06%, P<.0001). Aspirin (hazard ratio [HR]: 2.75, 95% confidence interval [CI]: 2.06-3.65), NSAIDs (HR: 8.61, 95% CI: 3.28-22.58), steroids (HR: 10.50, 95% CI: 1.98-55.57), SSRIs (HR: 11.71, 95% CI: 1.40-97.94), PPIs (HR: 8.47, 95% CI: 2.26-31.71), and H2RAs (HR: 10.83, 95% CI: 2.98-39.33) were significantly associated with LGIB. CONCLUSIONS: The risk of LGIB was higher in low-dose aspirin users than in aspirin nonusers in this nationwide cohort. Low-dose aspirin, NSAIDs, steroids, SSRIs, PPIs and H2RAs were independent risk factors for LGIB.

Elevated C-reactive protein level in hemodialysis patients with moderate/severe uremic pruritus: a potential mediator of high overall mortality.

BACKGROUND: Dialysis patients with uremic pruritus have worse outcomes. However, the pathophysiology of the high mortality in these patients remains inconclusive except for links with calcium/phosphate imbalance and sleep disturbance. Whether inflammation, an outcome predictor in dialysis patients, plays a role is unknown. METHODS: This prospective study included 321 chronic hemodialysis (HD) patients (>3 months) for survival analysis. A visual analog scale (VAS) was used to measure the severity of itching, and the patients were divided into four groups: no pruritus (VAS = 0, N = 118), mild (VAS 1-3, N = 76), moderate (VAS 4-7, N = 89) and severe pruritus (VAS 8-10, N = 38). The Pittsburgh Sleep Quality Index (PSQI) was used to define sleep disturbance, while high-sensitive C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) were used to evaluate inflammation. The patients were followed-up for 30 months. RESULTS: Patients with moderate/severe pruritus had higher hs-CRP, but similar TNF-α levels; they also had a worse survival rate (P = 0.0197, log rank test). By stratifying hs-CRP levels, those with higher hs-CRP had worse survival regardless of the severity of uremic pruritus. In a Cox proportional hazard model, hs-CRP levels and moderate/severe uremic pruritus were independent predictors of mortality after adjusting for age, poor sleeper (PSQI > 5), diabetes, albumin, phosphate, hemoglobin and parathyroid hormone levels and (hs-CRP) × (moderate/severe uremic pruritus) (all P < 0.05). CONCLUSION: In moderate/severe pruritic HD patients, those with higher hs-CRP suffer from worse overall mortality. Inflammation may bridge uremic pruritus to high mortality, and elevated hs-CRP predicts a worse outcome in this population.

Association between dyslipidemia and residual renal function in patients on chronic peritoneal dialysis.

BACKGROUND: Dyslipidemia and residual renal function (RRF) have a significant impact on the cardiovascular mortality in dialysis patients, but their association in patients on chronic peritoneal dialysis (PD) has not been completely studied. METHODS: 170 PD patients were divided into 2 groups based on the RRF (Group I had no RRF and Group II had RRF >0 ml/min/1.73 m2 BSA). An observational, longitudinal study was performed to elucidate the dyslipidemic state in PD patients with different levels of RRF and the association of dyslipidemia and deterioration of RRF during 3 years. RESULTS: Patients' basic characteristics and lipid profiles at the initiation of study were similar between the groups. At the end of study, Group I patients had a lower T-CHO (p=0.001), LDL-C (p=0.018), HDL-C (p=0.05) and non-HDL-C (p=0.003) than Group II. There was a significant correlation between a change in HDL-C and the decline of RRF (r=0.177, p=0.048) and it was independent of PD duration and levels of highly sensitive C-reactive protein (r=0.233, p=0.04). CONCLUSION: Our results clearly demonstrate the different longitudinal changes of lipid profiles in PD patients with different RRF and an association between decline of HDL-C and deterioration of RRF.

Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases.

Proteinuria (albuminuria) reflects dysfunction of the glomerular permeability barrier in which inflammatory cytokines play a key role. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses potent anti-inflammatory and immunomudulatory effects. This study evaluated the effectiveness of PTX to reduce proteinuria and inflammatory mediators in patients with proteinuric primary glomerular diseases. Seventeen patients with primary glomerular diseases, a persistent spot proteinuria exceeding 1.5 g/g creatinine (Cr) and a glomerular filtration rate between 24 and 115 ml/min/1.73 m(2) were treated with PTX 400 mg twice daily for 6 months. Before and after the treatment, serum Cr, plasma renin activity and aldosterone concentrations, plasma and urinary tumor necrosis factor (TNF)-alpha, interleukin-1beta and monocyte chemoattractant protein (MCP)-1, as well as urinary protein and Cr were measured. PTX significantly reduced urinary protein excretion, along with an increase of serum albumin. A significant correlation existed between the basal urinary protein/Cr and the basal urinary MCP-1/Cr ratios. PTX lowered the urinary MCP-1/Cr ratio, and the percent reduction of urinary protein/Cr ratio correlated directly with the precent decrease of urinary MCP-1/Cr ratio after PTX treatment. There was no significant change in blood pressure, renal function, biochemical parameters, plasma renin activity and aldosterone concentrations, or plasma TNF-alpha and MCP-1 levels during the study. In conclusion, administration of PTX 800 mg per day is safe and effective for reducing proteinuria in patients with proteinuric primary glomerular diseases. This beneficial effect occurs in close association with a reduction of urinary MCP-1 excretion.

Serum soluble transferrin receptor reflects erythropoiesis but not iron availability in erythropoietin-treated chronic hemodialysis patients.

BACKGROUND: The diagnosis of iron deficiency using the current commonly used tests is usually difficult in hemodialysis patients. Soluble transferrin receptor (sTfR) has caught the attention of physicians recently as regards its use as a parameter for the evaluation of iron status. This study was conducted in order to evaluate the correlation of serum soluble transferrin receptor (sTfR) concentration with hematological parameters and iron profiles, in the role of identifying iron deficiency among dialysis patients. METHODS: Seventy-three patients having received chronic hemodialysis and stable maintenance recombinant human erythropoietin (rHuEPO) therapy were included. Iron, total iron-binding capacity, ferritin and sTfR were measured in the first week. Following this, these patients began to receive intravenous iron dextran (2 mg/kg/week) for 4 weeks. The hematocrit (Hct), hemoglobin (Hb) levels and reticulocyte counts were evaluated weekly. At the beginning of fifth week, the sTfR level was measured again. Patients were classified as belonging to one of the following groups: serum ferritin < 100 microg/L - absolute iron-deficient group; initial ferritin level > or = 100 microg/L with an increase in hemoglobin of greater than 1 g/dL at the end of the study occult iron deficiency group; others - non iron-deficient group. RESULTS: Seventy-one patients completed the study. The concentration of sTfR was positively correlated with Hct, Hb and reticulocyte index at the beginning (r = 0.236, p = 0.047; r = 0.257, p = 0.04; r = 0.401, p < 0.01, respectively) and at the end of the study (r = 0.384, p < 0.01; r = 0.338, p < 0.01; r = 0.427, p < 0.001, respectively). After 4 weeks of iron and rHuEPO therapy, the sTfR concentration increased, rather than declined, from 21.85 +/- 8.06 nM to 23.76 +/- 7.42 nM (p = 0.04) and the change was positively correlated with the changes in Hct, Hb and reticulocyte index. The administered rHuEPO doses did not differbetween the iron deficiency group (absolute deficiency, n = 3; occult deficiency, n = 10) and non-iron deficiency group (n = 58). The sTfR levels failed to identify the occult iron deficiency group because there was no difference between occult iron-deficient and non-iron-deficient patients (24.73 +/- 9.09 nM versus 21.60 +/- 7.89 nM, p = 0.34). Instead, transferrin saturation (TS) could be a differential marker between the 2 groups (19.0 +/- 10.9% versus 30.1 +/- 12.7%, p = 0.012). CONCLUSION: The serum sTfR concentration is indeed an appropriate marker for erythropoiesis. The erythropoitic effect of administered rHuEPO could mask the effect of iron status on the sTfR concentration. This might make the sTfR concentration no longer an appropriate index to identify the presence of occult iron deficiency. Thus, TS and ferritin currently remain better methods for the evaluation of iron status in rHuEPO-treated chronic hemodialysis patients.

High resistive index of the radial artery is related to early primary radiocephalic hemodialysis fistula failure.

Forty-nine patients who had received radiocephalic hemodialysis fistula construction were evaluated with duplex Doppler ultrasonography to characterize the Doppler indices of the feed radial arteries just proximal to the site of anastomosis. Forty-four patients had fistulas with good function, and 5 patients had fistulas with inadequate blood flow or thrombosis within 4 weeks after the operation. A preliminary study showed extensive variability in peak systolic velocity and end-diastolic velocity in the feed arteries. The resistive index dropped significantly 1 week after the operation and remained relatively constant over the following 5 weeks. In the success group, the mean resistive index measured 1 week after operation was 0.40+/-0.06. It was higher than that of the failure group (mean resistive index: 0.52+/-0.06). Among patients with well-functioning fistulas, diabetic patients had higher resistive indices than did non-diabetic patients (0.44+/-0.04 vs. 0.37+/-0.06). Our results suggest that a higher resistive index of the feed artery is closely related to early autogenous primary hemodialysis fistula failure.

Dipyridamole inhibits TGF-beta-induced collagen gene expression in human peritoneal mesothelial cells.

BACKGROUND: Peritoneal matrix accumulation is characteristic of peritoneal fibrosis (PF). Continuous ambulatory peritoneal dialysis (CAPD) patients who had persistent transforming growth factor-beta (TGF-beta) in their drained effluent had an increased risk of PF. We previously reported that TGF-beta stimulates the expression of types I and III collagen mRNA in cultured human peritoneal mesangial cells (HPMCs), which may predispose them to develop PF. Pharmacological interventions to attenuate TGF-beta-stimulated matrix accumulation in HPMC may have therapeutic potential for the treatment of PF. The SMAD family and the extracellular signal-regulated protein kinase (ERK1/2, p44/p42) pathways have been shown to participate in TGF-beta signaling. Our current study identified these signal pathways in HPMCs and investigated the molecular mechanisms involved in the inhibitory effects of dipyridamole on TGF-beta-induced collagen gene expression in HPMCs. METHODS: HPMCs were cultured from human omentum by an enzyme digestion METHOD: Expression of collagen alpha1(I) mRNA was determined by Northern blotting. The SMAD proteins and the ERK1/2 activity were determined by Western blotting. RESULTS: TGF-beta-stimulated collagen alpha1(I) mRNA expression of HPMC was inhibited by dipyridamole in a dose-dependent manner. Smad2 and ERK1/2 were activated in response to TGF-beta; however, TGF-beta had little effect on the protein expression of Smad4. The addition of PD98059, which blocked activation of ERK1/2, suppressed TGF-beta-induced collagen alpha1(I) mRNA expression in a dose-dependent manner. At a concentration that inhibited collagen gene expression (17 microg/mL), dipyridamole suppressed ERK1/2 activation by TGF-beta. In contrast, the same concentration of dipyridamole had no effect on TGF-beta-induced activation of Smad2. CONCLUSION: Dipyridamole inhibits TGF-beta-induced collagen gene expression in HPMC through modulation of the ERK pathway. Our study of dipyridamole may provide therapeutic basis for clinical applications in the prevention of PF.

Dipyridamole inhibits PDGF-stimulated human peritoneal mesothelial cell proliferation.

BACKGROUND: It has been proposed that proliferation of human peritoneal mesothelial cells (HPMCs) accompanied by collagen synthesis may contribute to the development of peritoneal fibrosis (PF) in patients of long-term continuous ambulatory peritoneal dialysis (CAPD). However, the precise molecular mechanism regulating HPMC proliferation has never been reported. Dipyridamole has been reported to have potential as an antiproliferative and antifibrotic agent. We investigated the mechanism and effect of dipyridamole in regulation of HPMC proliferation. METHODS: HPMCs were cultured from human omentum by an enzyme digestion METHOD: Cell proliferation was measured by the methyltetrazolium assay and intracellular cAMP was measured using an enzyme immunoassay kit. Cell-cycle distribution of HPMC was analyzed by flow cytometry. Extracellular signal-regulated protein kinase (p44/p42 ERK) activity and expressions of cell-cycle proteins (cyclin D(1), CDK4, pRB and p27(Kip1)) were determined by Western blotting. RESULTS: The addition of DP suppressed PDGF-stimulated HPMC proliferation by cell-cycle arrest at the G1 phase. The antimitogenic effect of dipyridamole was mediated through the cAMP pathway. PDGF (25 ng/mL) increased the ERK1/2 activity of HPMC within 15 minutes, which maximized at 30 minutes, and the pretreatment with dipyridamole (17 microg/mL) substantially reduced the ERK response to PDGF by approximately 78.5%. PDGF induced elevated protein levels of cyclin D(1), but the CDK4 protein level did not change. Dipyridamole and DBcAMP had no effect on the levels of cyclin D(1) and CDK4 in PDGF-stimulated HPMC. PDGF decreased p27(Kip1) and induced pRB phosphorylation of HPMC. In contrast, dipyridamole prevented PDGF-induced p27(Kip1) degradation and attenuated PDGF-stimulated pRB phosphorylation. CONCLUSION: Dipyridamole appears to inhibit PDGF-stimulated HPMC proliferation through attenuated ERK activity, preservation of p27(Kip1), and decreased pRB phosphorylation. Thus, dipyridamole may have therapeutic efficacy to prevent or alleviate PF.

Association of hypertriglyceridemia and insulin resistance in uremic patients undergoing CAPD.

OBJECTIVE: Hyperlipidemia is frequently encountered in uremic patients and may be worsened by continuous ambulatory peritoneal dialysis (CAPD) treatment. The lipid abnormalities in these patients may be multifactorial. Insulin resistance (or its compensatory hyperinsulinemia) is commonly observed in uremic patients, but its association with hyperlipidemia in these patients has not been studied. PATIENTS AND METHODS: Lipid profiles of 35 nondiabetic nonobese patients undergoing CAPD for more than 1 year (mean 52.3 months) were studied. Current laboratory data and parameters related to peritoneal dialysis (PD) within the previous 3 months were recorded. After overnight fasting and interruption of PD, an oral 75-g glucose tolerance test (OGTT) was examined. RESULTS: After CAPD treatment for more than 12 months, these patients had higher serum triglyceride (TG) (p = 0.001) and total cholesterol (p = 0.0058) levels than their values before commencing CAPD. Twelve of 14 patients with serum TG higher than 200 mg/dL (high-TG) were diagnosed de novo, in contrast with only 1 patient diagnosed of de novo hypercholesterolemia (total cholesterol > 240 mg/dL). There was no difference in age, gender, body mass index (BMI), duration of PD treatment, serum albumin, hematocrit, intact serum parathyroid hormone (iPTH), peritoneal glucose load, solute transport, or weekly Kt/V urea between normal-TG and high-TG patients. After adjusting for age, gender, BMI, weekly Kt/V urea, and iPTH, the high-TG patients had higher levels of area under the curve for glucose (AUC(Glu)), area under the curve for insulin (AUC(Ins)), and AUC(Ins)/AUC(Glu) ratios (F = 10.63, 10.14, and 8.65; p = 0.0029, 0.0035, and 0.0065, respectively), indicating that the high-TG patients were more insulin resistant. There were 24 patients with normal glucose tolerance (NGT), and 11 patients with impaired glucose tolerance (IGT). The IGT group had higher serum TG (F = 10.43, p = 0.003) and total cholesterol (F = 8.05, p = 0.009) than the NGT group, after adjusting for BMI, duration of CAPD treatment, peritoneal glucose load, solute transport, serum albumin, and lipid levels before PD treatment. TheTG levels after CAPD treatment were positively correlated with AUC(Glu), AUC(Ins), and AUC(Ins)/AUC(Glu) ratio (r = 0.48, 0.53, and 0.49; p = 0.0037, 0.001, and 0.0028, respectively). CONCLUSIONS: These results indicate that insulin resistance is an important factor in the development of hypertriglyceridemia in CAPD patients.

Systemic lupus erythematosus and peritoneal dialysis: outcomes and infectious complications.

OBJECTIVE: Systemic lupus erythematosus (SLE) is the most common secondary glomerulonephritis resulting in end-stage renal disease (ESRD) among young adults in Taiwan. Studies of the infectious complications and outcomes among such SLE patients undergoing peritoneal dialysis (PD) are limited. DESIGN: A retrospective age- and gender-matched case control study. SETTING: A university teaching hospital. PATIENTS: There were 23 SLE patients with ESRD receiving PD for more than 3 months during the past 15 years. Another 46 age- and gender-matched non-SLE nondiabetic patients receiving PD were selected as the control group in this study. INTERVENTION: All patients underwent PD as renal replacement therapy and were regularly followed up at this hospital. MAIN OUTCOME MEASURES: Technique survival and incidences of exit-site infection (ESI) and peritonitis in these patients. RESULTS: The SLE patients had a lower predialysis serum albumin than the control group (3.16 +/- 0.50 g/dL vs 3.52 +/- 0.50 g/dL, p < 0.01). The incidences of exit-site infection (ESI) and peritonitis were higher for SLE patients than for control patients (p < 0.01 and p < 0.001, respectively). Kaplan-Meier survival analysis indicated that SLE patients had shorter time intervals to first infectious complications, and poorer technique survival. Infection was the major cause of dropout and mortality in the SLE patients. The SLE patients had a reduced chance of receiving a renal transplant. The use of steroids by SLE patients was associated with a higher incidence of peritonitis (p = 0.04), but association with ESI was insignificant. In a Cox regression model, the underlying SLE was the only risk factor for technique failure and time interval to first infectious complication. CONCLUSION: SLE patients undergoing PD are more susceptible to infection than age- and gender-matched non-SLE nondiabetic patients and have poorer technique survival. Systemic lupus erythematosus itself may further compromise the immunity of uremic patients.

Dipyridamole inhibits human peritoneal mesothelial cell proliferation in vitro and attenuates rat peritoneal fibrosis in vivo.

BACKGROUND: Peritoneal fibrosis (PF) is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Proliferation of human peritoneal mesothelial cells (HPMC) and matrix over-production are regarded as the main processes predisposing to PF. Dipyridamole (DP) has been reported to have potential as an antiproliferative and antifibrotic agent. We thus investigated the effect of DP in inhibiting proliferation and collagen synthesis of HPMC. A rat model of peritonitis-induced PF was also established to demonstrate the in vivo preventive effect of DP. METHODS: HPMC was cultured from human omentum by an enzyme digestion METHOD: Cell proliferation was measured by the methyltetrazolium assay. Intracellular cAMP was measured using an enzyme immunoassay (EIA) kit. Total collagen synthesis was measured by (3)H-proline incorporation assay. Expression of collagen alpha1 (I) and collagen alpha 1 (III) mRNAs was determined by Northern blotting. The rat model of peritonitis-induced PF was developed by adding dextran microbeads (Cytodex, 8 mg/1 mL volume) to a standardized suspension (3 x 10(9)) of Staphylococcus aureus. DP was administrated via intravenous infusion (4 mg in 1 h) daily for seven days. Macroscopic grading of intraperitoneal adhesions and histological analyses of peritoneal thickness and collagen expression were performed. RESULTS: Addition of DP to HPMC cultures suppressed serum-stimulated cell proliferation and collagen synthesis. The antimitogenic and antifibrotic effects of DP appear to be predominantly mediated through the cAMP pathway, as DP increased intracellular cAMP in a dose-dependent manner. The macroscopic grade of intraperitoneal adhesion and peritoneal thickness were both significantly increased in animals treated with Cytodex plus S. aureus; on the other hand, DP attenuated these fibrotic changes with statistical significance (P < 0.01). Analysis of gene expression of collagen alpha 1 (I) and alpha1 (III) in the peritoneal tissue of experimental animals yielded similar results. CONCLUSIONS: This study suggests that dipyridamole may have therapeutic potential in treating peritoneal fibrosis.

Comparison of infectious complications in peritoneal dialysis patients using either a twin-bag system or automated peritoneal dialysis.

BACKGROUND: Automated peritoneal dialysis (APD) and twin-bag (TB) systems are two major peritoneal dialysis (PD) modalities. Published data comparing the infectious complications of these modalities is limited. Subjects and methods. Ninety-five patients using APD (the APD group) and 117 patients using TB system (the TB group) were recruited. Among them, 35 patients used both modalities. The two groups' clinical characteristics, incidences of infectious complications, and the time intervals to first PD-related infection were compared. RESULTS: Clinical characteristics, incidence of exit-site infection (ESI), and time intervals to first ESI were similar in the TB and APD groups. The incidence of peritonitis in the APD group (1.22 episodes/100 patient-months) was significantly (P < 0.001) lower than that of the TB group (2.28 episodes/100 patient-months). Using the Cox proportional hazard model, APD was found to have a lower risk of peritonitis relative to TB systems, with marginal significance (RR 0.58, P = 0.051). CONCLUSION: APD was found to have a lower peritonitis rate than the TB system. Since reducing the peritonitis rate helps to maintain technical survival during PD, from this viewpoint, APD may be preferred for patients undergoing PD, unless contraindicated.

Chronic fatigue in long-term peritoneal dialysis patients.

OBJECTIVE: Fatigue is a common symptom in long-term dialysis patients. This study investigated possible clinical factors which may cause the development of fatigue in patients receiving peritoneal dialysis (PD). We also investigated the relationship between total solute clearance (TSC) and fatigue symptoms in PD patients. DESIGN: A cross-sectional study design was used to compare the clinical characteristics among groups of PD patients classified by different degrees of fatigue. The relationship among dialysis adequacy (including Kt/V(urea) and weekly creatinine clearance; C(cr)), clinical characteristics and fatigue symptoms were also assessed. SETTING: The PD unit of a major university teaching hospital in Taipei, Taiwan. PATIENTS: Consecutive patients who had received PD for a minimum duration of 4 months were recruited for participation in the study. Patients were excluded if they had a history of ischemic heart disease, severe heart failure (NYHA function III or IV), malignant neoplasm, active infection, major psychiatric problems, chronic obstructive pulmonary disease, or disturbed consciousness. Finally, a total of 64 patients, 31 of whom were receiving continuous ambulatory peritoneal dialysis and 33 who were receiving continuous cycling-assisted peritoneal dialysis, were enrolled in the study. METHODS: Fatigue was evaluated using a specially designed questionnaire that includes fourteen items. Patients were divided into three groups according to their fatigue scores (FS): mild (FS, 0-3), moderate (FS, 4-8), and severe (FS, 9-14) fatigue. The demographic data, dialysis variables, and clinical parameters of patients were compared among these groups. The relationship between fatigue and TSC was also examined. RESULTS: The FS were correlated with serum intact parathyroid hormone (iPTH) level and total cholesterol concentration (p < 0.05). A linear correlation was also noted between serum iPTH level and total cholesterol level. When the patients were divided into an adequate- and an inadequate-dialysis group according to values of TSC, Kt/V(urea) as well as weekly creatinine clearance, a significant correlation was found between weekly C(cr) and FS. CONCLUSION: This study has demonstrated that dialysis adequacy plays a key role in the development chronic fatigue. In addition, weekly C(cr) was better correlated with fatigue than Kt/V(urea).

Relationship between dialysis adequacy and quality of life in long-term peritoneal dialysis patients.

OBJECTIVE: The purpose of this study was to compare quality of life (QOL) between peritoneal dialysis (PD) patients with adequate and inadequate total solute clearance (TSC). We also tried to determine the relationship between QOL and TSC. DESIGN: A cross-sectional study design was used in which QOL was evaluated and compared between PD patients with adequate and inadequate TSC. SETTING: The PD unit of a university teaching hospital. PATIENTS: Sixty-seven patients were recruited, 38 on continuous ambulatory PD and 29 on continuous cyclerassisted PD. METHODS: Patients were divided into adequate and inadequate groups, based on the results of either total urea clearance (Kt/Vurea) or total creatinine clearance (weekly CCr). The demographic data, dialysis variables, and clinical parameters of these patients were all collected. QOL was evaluated using the SF-36 questionnaire, which contains eight domains and is a comprehensive and validated instrument for QOL evaluation. QOL of patients in adequate and inadequate groups was compared. The relationship between QOL and TSC was also examined. RESULTS: Among patients grouped by Kt/Vurea, patients in the adequate group had significantly higher scores in two domains of the SF-36, that is, physical and emotional role functioning, than did those in the inadequate group. The total SF-36 scores were positively correlated with Kt/Vurea when all patients were pooled together. However, among patients grouped by weekly CCr, there was no significant difference in any of the eight domains of the SF-36 between patients in the adequate and inadequate groups. No correlation was found between the total SF-36 scores and weekly CCr. CONCLUSION: Our study had two important findings: First, PD patients with adequate total solute clearance, based on Kt/Vurea and not on weekly CCr, had a better QOL. Second, Kt/Vurea is better correlated with QOL than weekly CCr. These findings suggest that Kt/Vurea is a better parameter for the clinical evaluation of total solute clearance from the viewpoint of QOL.

Incidence of exit-site infection with various exchange systems in continuous ambulatory peritoneal dialysis.

BACKGROUND AND PURPOSE: The disconnect twin-bag (TB) system was first introduced in Taiwan for use as an exchange system in continuous ambulatory peritoneal dialysis (CAPD) in 1995. Following its introduction, the incidence of CAPD-associated peritonitis declined, but the incidence of exit-site infection (ESI) increased. To determine the cause of the increase in ESI incidence after the introduction of the TB system, this study compared the incidence of ESI among patients using the O set, ultraviolet antiseptic (UV) device, and the TB system. METHODS: A total of 170 patients who had received CAPD for more than 3 months were enrolled in this study. Poisson test and Kaplan-Meier survival analysis were used to compare the ESI incidence and ESI-free catheter survival among patients using the O set, UV device, or TB system. Cox stepwise forward proportional hazard analysis was used to assess the impact of sex, education, cause of uremia, age, and type of exchange system on ESI. RESULTS: The incidences of ESI differed significantly among patients using the three exchange systems, with 20.9, 13.8, and 4.0 episodes per 100 patient-years for patients using the TB system, O set, and UV device, respectively. New patients using the TB system also had a shorter mean interval of ESI-free catheter survival than those using the UV device (26.9 vs 58.8 months, p = 0.002). In the Cox stepwise forward proportional hazard analysis, non-lupus patients had a lower risk of developing ESI than lupus patients (relative risk [RR] 0.40, p = 0.03). The RR of ESI in patients using the UV device was also lower than in those using the TB system (RR 0.15, p < 0.01). CONCLUSION: In this study, use of the TB system was associated with a higher incidence of ESI. The increased ESI incidence may be related to the heavier mini-transfer set of the TB system. Therefore, special attention should be given to fastening the mini-transfer set tightly during the exchanging procedure to prevent traction on the exit-site, which is associated with an increased incidence of subsequent ESI.

Clinical features of and risk factors for fungal peritonitis in peritoneal dialysis patients.

BACKGROUND AND PURPOSE: Fungal peritonitis (FP) is a serious complication for peritoneal dialysis (PD) patients and can result in technical failure and mortality. Catheter removal remains the mainstay of treatment. This study sought to identify the risk factors for FP in order to facilitate the prevention of this catastrophic complication. METHODS: A total of 246 patients who received long-term PD from 1985 to 1998 were included in this retrospective study. Twenty episodes of FP occurred in 19 patients. The clinical characteristics, pathogens, treatment modalities, and outcomes of the FP episodes were retrospectively reviewed. The FP incidence in various demographic and clinical groups, classified according to sex, age, education, and underlying cause of uremia, were compared with the Poisson test. RESULTS: Thirteen episodes of FP were caused by yeast, and the remaining episodes were caused by Aspergillus spp. Age, sex, and education did not affect the FP incidence. Lupus patients (969 patient-months) had a higher incidence of FP than patients with other underlying diseases (p < 0.05). The 19 FP patients also had a higher incidence of bacterial peritonitis than other PD patients (p < 0.01). Among the 20 FP episodes, 14 (70%) were preceded by antibiotic use, and eight (40%) developed during hospitalization. Steroids were used at the time of FP in five of six lupus patients. Seven patients (37%) died within 1 month after diagnosis of FP. Five patients were able to remain on PD after FP, but only three patients were able to maintain catheter placement. CONCLUSION: The risk factors for FP identified in this study include the use of antibiotics and steroids, underlying lupus, frequent occurrence of bacterial peritonitis, and hospitalization. Antifungal therapy may allow the catheter to be kept in place in a few patients, but catheter removal should be considered in patients whose FP is refractory to medical treatment.

Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis: effects on TGF-beta.

BACKGROUND: Prevention or treatment of peritoneal fibrosing syndrome has become an important issue in patients on continuous ambulatory peritoneal dialysis (CAPD). Recent evidence has suggested that mesothelial stem cell proliferation and matrix over-production predispose the development of peritoneal fibrosis. We investigated whether pentoxifylline (PTX) affects human peritoneal mesothelial cell (HPMC) growth and collagen synthesis. METHODS: HPMC was cultured from human omentum by an enzymic disaggregation method. Cell proliferation was assayed using a methyltetrazolium uptake method. Cell cycle analysis was performed by flow cytometry. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Prostaglandins and cAMP were determined by enzyme immunoassay. Northern blot analysis was used to determine mRNA expression. RESULTS: Our data show that PTX inhibited serum-stimulated HPMC growth and collagen synthesis in a dose-dependent manner. Cell cycle analysis showed that PTX arrested the HPMCs in the G1 phase. PTX decreased the procollagen alpha1 (I) mRNA expression either stimulated by serum or transforming growth factor-beta (TGF-beta). PTX did not alter prostaglandins synthesis but dose-dependently increased intracellular cAMP level. PTX, the same as 3-isobutyl-l-methylxanthine, could potentiate prostaglandin E1 (PGE1) increased cAMP levels of HPMC. The antimitogenic and antifibrogenic effects of PTX on HPMC were reversed by N-[2]-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89). Therefore, the mechanism of these effects may be due to the phospodiesterase inhibitory property of PTX. CONCLUSIONS: These data suggest that PTX may have a role in treating peritoneal fibrosing syndrome.

Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma.

BACKGROUND: Tumor venous invasion in patients with resectable hepatocellular carcinoma (HCC) is frequent and can be macroscopic and microscopic or microscopic alone. Although macroscopic invasion is a well-established prognostic indicator, the clinical significance of microscopic invasion remains unclear. METHODS: There were 322 patients enrolled who had undergone curative resection for HCC. The clinicopathologic factors and prognostic significance associated with macroscopic and microscopic venous invasion were analyzed. RESULTS: Macroscopic invasion was observed in 50 patients (15.5%) and microscopic invasion in 190 (59.0%). The larger the tumor, the more the incidence of venous invasion. There were 140 patients with microscopic invasion only (Group 1). Patients with macroscopic invasion (Group 2, n = 50) also had microscopic invasion. Compared with patients without venous invasion (Group 3, n = 132), Group 1 had a higher alpha-fetoprotein level, a larger tumor size, and more tumors without encapsulation. For group 1, the 1-, 3-, and 5-year disease-free survival rates were 65.6%, 41.6%, and 30.8%, respectively. The 1-, 3-, and 5-year overall survival rates were 87. 8%, 60.0%, and 52.7%, respectively. The survival rates of group 1 were lower than those of group 3 and higher than those of group 2 (P <.05). Multivariate analysis indicated that microscopic and macroscopic venous invasion, surgical margin, indocyanine-green retention, and tumor size and number were significant predictors of postresectional survival. CONCLUSIONS: In HCC patients, microscopic venous invasion is frequent and related independently to postresectional outcome.