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Philip Kam-Tao Li

Publications and source records attributed to Philip Kam-Tao Li.

At least 19 recordsLinked to original sources

Continuous ambulatory peritoneal dialysis peritonitis: broth inoculation culture versus water lysis method.

BACKGROUND/AIM: In the setting of empiric antibiotic treatment of peritoneal-dialysis-related peritonitis complications, the speed with which a bacteriological diagnosis can be achieved is of importance. We compare the clinical performance of two culture methods to diagnose the causative microorganisms as suggested by the International Society for Peritoneal Dialysis and the United Kingdom Health Protection Agency. METHODS: We prospectively evaluated microbiological cultures of peritoneal fluid samples by the direct broth culture versus water lysis. Samples from 17 consecutive patients with dialysis-associated peritonitis were examined. RESULTS: Of the 17 dialysates cultured, 14 (82.4%) were positive by one of the two methods. The final culture results agreed in 16 of 17 specimens (94.1%). The preliminary organism identification rate by Gram staining with the broth culture method was 70.6%, which was significantly greater than 17.6% by the water lysis method (p = 0.0019). In particular, the broth culture technique demonstrated superior Gram stain performance to identify Gram-positive organisms. Among the 13 dialysate samples positive by both methods, the broth culture method detected organisms faster than the water lysis method (1.3 +/- 0.7 vs. 2.6 +/- 1.6 days, p = 0.005). CONCLUSIONS: Our results support the routine use of the broth culture technique using BacT/Alert blood culture bottles in order to facilitate early streamlining of empiric antibiotic therapy. Gram staining of sediments after centrifugation is associated with low diagnostic yield. Whether the lysis-centrifugation technique could provide additional value in case of peritonitis with a high likelihood of culture-negative results needs to be evaluated.

Aged↗

Adherence to peritoneal dialysis training schedule.

BACKGROUND: Shortening behaviour during peritoneal dialysis training can be easily measured, and likened to the skipping behaviour in haemodialysis subjects, although its effect on peritoneal dialysis outcomes is now well understood. We studied the clinical impact of failing to adhere to a peritoneal dialysis training programme among incident dialysis patients. METHODS: This study included 159 consecutive inception peritoneal dialysis patients in a single centre from September 1999 through November 2002. We evaluated the effects of behavioural compliance quantified by the per cent time arriving late for scheduled peritoneal dialysis training. The patients were categorized by whether they arrived late in >20% of their peritoneal dialysis training sessions. RESULTS: Of the 159 incident peritoneal dialysis patients (mean age 57 +/- 13 years) who attended peritoneal dialysis training, 70 subjects (44%) arrived late in >20% of the sessions. They were younger by 5 years than patients who arrived late < or =20%. Mean peritonitis-free time for subjects who arrived late for training in >20% the of sessions was 30.9 months, as compared with 41.8 months in subjects with < or =20% late attendance behaviour (log rank test, P = 0.038). Multivariable Cox proportional hazards analysis showed that late attendance behaviour and baseline serum albumin were the only independent risk factors for the time to a first peritonitis after adjustment for diabetes mellitus and relevant coexisting medical factors. Late arrival in >20% of the peritoneal dialysis training sessions was associated with >50% increased likelihood of subsequent peritonitis, with an adjusted risk ratio of 1.56 (95% confidence interval, 1.02-2.39; P = 0.04). CONCLUSION: These findings show that the behavioural measure of late attendance for peritoneal dialysis training has a crucial role in predicting peritonitis. It may therefore represent a practical strategy for identifying poor adherence or predicting medical outcomes.

Adolescent↗

Clinical biocompatibility of a neutral peritoneal dialysis solution with minimal glucose-degradation products--a 1-year randomized control trial.

BACKGROUND: Chronic utilization of a bio-incompatible peritoneal dialysis (PD) solution with acidic pH and a high content of glucose degradation product (GDP) has been implicated as a contributing cause of peritoneal failure. We compared a newly formulated solution of neutral pH and low levels of GDP to a standard PD solution. METHODS: Fifty new PD patients were randomized to a conventional lactate-buffered fluid (control) and a pH neutral, lactate-buffered, low GDP solution (balance). Patients were followed for 12 months. Serum samples were assayed for C-reactive protein (CRP). PD effluent was collected and assayed for cancer antigen-125 (CA125) and hyaluronan (HA). Clinical end points were the residual renal function and dialysis adequacy indices. RESULTS: After 52 weeks of treatment, PD fluid CA125 rose from 2.45 +/- 0.96 to 14.30 +/- 2.17 U/ml (P < 0.001), and HA declined from 2.26 +/- 0.60 to 1.45 +/- 0.32 mug/ml (P = 0.07) in the balance group. The balance group had a higher PD fluid CA-125 (14.30 +/- 2.17 vs 7.36 +/- 2.23 U/ml, P = 0.007), lower HA (1.45 +/- 0.32 vs 2.55 +/- 0.32 mug/ml, P = 0.007), and lower serum CRP level (1.77 +/- 0.42 vs 7.73 +/- 2.42 mg/l, P = 0.026) than the control group at 52 weeks. There was no difference in dialysis adequacy indices, ultrafiltration volume, urine output, residual renal function, peritonitis rate or need of hospitalization in 1 year. CONCLUSION: As compared to conventional PD solution, the use of balance, a neutral pH, low GDP solution resulted in a superior profile of PDE mesothelial cell marker and a lower degree of systemic inflammation, and the difference was maintained for 1 year. It remains to be determined whether these effects could result in better long-term clinical outcome.

Biomarkers↗

Connective tissue growth factor is responsible for transforming growth factor-beta-induced peritoneal mesothelial cell apoptosis.

BACKGROUND: Previous studies found that transforming growth factor-beta (TGF-beta) induces mesothelial production of connective tissue growth factor (CTGF), which may be downstream mediators of TGF-beta. Since high dose TGF-beta induces apoptosis of peritoneal mesothelial cells (PMC), we study the effect of CTGF blockade in the system of TGF-beta-induced PMC apoptosis. METHOD: We examined the effect of TGF-W in primary culture of rat peritoneal mesothelial cells (PMC). PMC apoptosis was studied by flow cytometry. The effect of CTGF was blocked by antibody and short-interfering RNA (siRNA). Expression of apoptotic gene was studied by real-time polymerase chain reaction. RESULT: In cultured unstimulated rat PMC, there is a low but definite incidence of spontaneous apoptosis. Stimulation with TGF-beta 50 pg/ml induces an upregulation of apoptotic gene BAX expression and a downregulation of anti-apoptotic gene BCL-2L expression, and a 4-fold increase in PMC apoptosis. The effect of TGF-beta-induced PMC apoptosis was partly prevented by antibody against CTGF, and completely abolished by CTGF-specific siRNA, while CTGF-blockade by siRNA had no effect on PMC necrosis. CTGF silencing by siRNA prevented the down-regulation of BCL-2L expression induced by TGF-beta, had no effect on the BAX expression. CONCLUSION: Our results indicate that CTGF is an important downstream mediator of TGF-beta-induced PMC apoptosis.

Animals↗

Antibody response to hepatitis B vaccine in end-stage renal disease patients.

BACKGROUND: This retrospective and comparative study evaluated the relationship between different factors which may contribute to suboptimal immunological response to intramuscular recombinant hepatitis B vaccine in end-stage renal disease (ESRD) subjects. METHODS: From a cohort of 64 dialysis subjects undergoing primary vaccination with Engerix-B, we determined the predictive factors that impinged on patients' response to vaccine, as defined by anti-HBs level > or = 10 mIU/l. Dose efficacy was further evaluated by comparing three historical cohorts vaccinated by the regimens of 20, 40 and 80 microg/dose, respectively. RESULTS: We identified 64 ESRD patients (mean age 43 +/- 12 years, 81% receiving peritoneal dialysis) who received primary vaccination from April 1997 to September 2004. Median follow-up was 6.5 years. They achieved 81% seroconversion rate. Older age, diabetes mellitus, obesity and low Engerix-B dose were risk factors of inadequate anti-HBs response by univariate analysis. By stepwise logistic regression analysis, hepatitis B vaccine dose was the only independent predictive factor of impaired antibody response. An Engerix-B vaccine dose of 20 microg was associated with more than tenfold increase in risk of non-response to hepatitis B vaccine (hazards ratio 32.2 (95% CI 3.85-250.0)). Immunization with 80 microg of Engerix-B increased the likelihood of persistent protective antibody (log-rank test, p = 0.014). Immunization with Engerix-B 80-microg dose is estimated to prevent one extra ESRD subject who would lose seroprotective anti-HBs level at 1 year for every 5.6 patients treated (number needed to treat to benefit, 5.6 (95% CI 5.4-5.8)). CONCLUSIONS: Our results suggest the potential for the three-dose schedule of recombinant vaccine Engerix-B 80 microg to prolong the immune response among ESRD population.

Adult↗

The effect of immunosuppressive therapy on the messenger RNA expression of target genes in the urinary sediment of patients with active lupus nephritis.

BACKGROUND: Previous studies have shown that messenger RNA (mRNA) expression of target genes is increased in the urinary sediment of patients with active lupus. We study the effect of immunosuppressive therapy on the urinary gene expression profile in patients with active lupus nephritis. Method. We recruited nine patients with active systemic lupus erythematosus (SLE) and renal disease, and required corticosteroid, with or without cytotoxic treatment. They were followed for 6 months, urine samples were collected at 0, 4, 12 and 24 weeks and gene expression profile was determined by polymerase chain reactions. The pattern of gene expression was compared to clinical parameters of therapeutic response. RESULTS: Amongst the target genes studied, there was a progressive decline in the urinary expression of T-bet, interleukin (IL)-10, transforming growth factor-beta (TGF-beta), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma (IFN-gamma) after immunosuppressive treatment, although the change of IFN-gamma was not statistically significant. The time course of their urinary expression was parallel to the systemic activity as reflected by the systemic lupus erythematosus disease activity index (SLEDAI). Throughout the study period, the SLEDAI score correlated significantly with the expressions of IFN-gamma (r = 0.43, P = 0.009), T-bet (r = 0.40, P = 0.016), TGF-beta (r = 0.51, P = 0.002) and MCP-1 (r = 0.38, P = 0.022). The anti-double strand(anti-ds)DNA antibody titer correlated significantly with the expressions of IFN-gamma (r = 0.45, P = 0.009), T-bet (r = 0.37, P = 0.034), IL-10 (r = 0.59, P<0.001), TGF-beta (r = 0.44, P = 0.010) and MCP-1 (r = 0.49, P = 0.004). On the other hand, the expression level of IL-2, IL-4, IL-12, IL-18 and GATA-3 remained static throughout the study period. CONCLUSIONS: The mRNA expression of T-bet, IL-10, TGF-beta, MCP-1, and probably IFN-gamma in the urinary sediment of patients with active lupus nephritis improves with successful immunosuppressive therapy, and the change in gene expression profile is in phase with the clinical disease activity. Measurement of urinary mRNA expression of target genes may be a potential non-invasive tool for the monitoring of lupus disease activity.

Adult↗

mRNA expression of target genes in the urinary sediment as a noninvasive prognostic indicator of CKD.

BACKGROUND: Study of messenger RNA (mRNA) expression of target genes in urinary sediment was suggested as a noninvasive marker of renal damage in patients with chronic kidney diseases (CKDs). We studied the relationship between urinary mRNA expression of target genes and risk for renal function deterioration in patients with CKD. METHODS: We studied 131 patients with CKD with kidney biopsy. mRNA expression of 11 target genes in urinary sediment was measured by means of quantitative polymerase chain reaction. Patients then were followed up for 27.4 +/- 10.1 months. The primary end point is doubling of serum creatinine concentration or end-stage renal disease. RESULTS: Thirty-six patients (27.5%) reached the primary end point during follow-up. Univariate analysis showed that sex, age, proteinuria, estimated glomerular filtration rate, histological diagnosis, degree of tubulointerstitial scarring, percentage of glomerulosclerosis, and urinary mRNA expression of hepatocyte growth factor (HGF) were predictors of the primary end point. At 24 months, event-free survival rates were 90.9% and 64.3% for patients with low and high urinary HGF expression, respectively (log rank test, P = 0.002). After adjusting for other confounding factors by using a Cox proportional hazard model, urinary HGF expression remained an independent predictor of the primary end point, and a 1-fold increase in expression was associated with a 4.0% (95% confidence interval, 0.5 to 7.5; P = 0.024) increase in risk. CONCLUSION: In the target genes examined, urinary HGF expression is an independent prognostic indicator of CKD after adjusting for confounding clinical and histological factors. Measurement of urinary HGF mRNA expression may be a useful noninvasive tool for risk stratification of patients with CKD.

Biopsy↗

Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study.

BACKGROUND: Previous studies showed that angiotensin-receptor blocker (ARB) therapy decreased proteinuria and possibly slowed the rate of renal function decline in patients with chronic proteinuric nephropathies. We performed a double-blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in the treatment of patients with immunoglobulin A (IgA) nephropathy. METHODS: From 6 centers, we recruited 109 patients with IgA nephropathy who had either: (1) proteinuria with protein greater than 1 g/d and serum creatinine level less than 2.8 mg/dL (< 250 micromol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL (120 to 250 micromol/L) regardless of degree of proteinuria. Patients were randomly assigned to administration of either valsartan, 80 mg/d (titrated up to 160 mg/d for blood pressure control), or placebo for 104 weeks. Additional antihypertensive therapy was allowed to achieve a target blood pressure of 140/90 mm Hg. The primary end point was doubling of serum creatinine level or dialysis-dependent renal failure. Secondary outcomes included change in proteinuria and decrease in glomerular filtration rate (GFR). RESULTS: There were 54 patients in the treatment group and 55 patients in the placebo group. Baseline clinical characteristics were similar between groups, although the treatment group had a marginally greater baseline GFR (87 +/- 36 versus 78 +/- 38 mL/min/1.73 m2 [1.45 +/- 0.60 versus 1.30 +/- 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria (protein, 1.8 +/- 1.2 versus 2.3 +/- 1.7 g/d; P = 0.21) than the placebo group. Average blood pressures during the study were 92.7 +/- 10.6 mm Hg in the treatment group and 100.9 +/- 9.1 mm Hg in the placebo group (P < 0.001). During the study period, 4 patients in the placebo group and 1 patient in the treatment group reached the primary end point (log-rank test, P = 0.18). Proteinuria decreased significantly in the treatment group (protein, 1.8 +/- 1.2 to 1.2 +/- 1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear regression models, valsartan treatment resulted in a 33.0% decrease in proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other confounding factors. There was a significant decrease in mean rate of GFR decrease in the valsartan-treated group (-5.62 +/- 6.79 mL/min/y [-0.09 +/- 0.11 mL/s/y]) compared with the placebo group (-6.98 +/- 6.17 mL/min/y [-0.12 +/- 0.10 mL/s/y]) throughout the study period after adjustment for average blood pressure and proteinuria (P = 0.014). CONCLUSION: Valsartan significantly decreases proteinuria and slows renal deterioration in patients with IgA nephropathy after adjustment for confounding factors, notably blood pressure. The long-term benefit of valsartan needs to be confirmed with additional studies.

Adult↗

Genetic polymorphism of vascular endothelial growth factor: impact on progression of IgA nephropathy.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in the capillary endothelial cell growth and proliferation and has known effects on glomerular microvascular permeability. Because certain VEGF polymorphisms are correlated with alterations in VEGF expression, we hypothesized that VEGF genetic polymorphisms may affect the renal survival and progression of primary IgA nephropathy. METHODS: The study population consisted of 195 biopsy-proven IgA nephropathy patients at our center between 1984 and 2004. VEGF genotype polymorphism at -2578 positions was determined from peripheral blood leukocytes DNA using polymerase chain reaction methodologies. The primary end point was kidney survival as measured by the time interval from renal biopsy to end-stage renal disease or the requirement of renal replacement therapy. RESULTS: In total, we studied 119 women (61%) and 76 men (39%), with a mean age of 35 +/- 10 yr at the time of renal biopsy. Observed genotype frequency was 55.6%, 38.8%, and 5.1% for CC, CA, and AA genotypes respectively. Baseline characteristics did not differ significantly between three genotype groups for patient age, sex, prevalence of hypertension, degree of proteinuria, initial serum creatinine concentration, and the histological grading. After a median follow-up period of 11 yr, doubling of the baseline serum creatinine occurred in 107 of them; 99 patients reached end-stage renal disease requiring renal replacement therapy with a median renal survival of 88 months. The kidney survival in the CC genotype subgroup was similar to that of the CA/AA genotype subgroup during the first 2 yr but became worse than the latter thereafter (log-rank test P = 0.023). The kidney survival rates at the end of 6 yr were 76.8% in the CA genotype, 67.0% in the CC, and 50.0% in the AA genotype groups. Unadjusted hazard ratio of developing end-stage renal disease was 2.65 (95% CI, 1.16 to 6.06) for the CC group as compared to the CA/AA group. The influence of VEGF genotype upon renal survival, however, was not significant after multivariate Cox regression analysis. CONCLUSION: Our preliminary results raise the concern that the CC genotype of the VEGF promoter at -2578 position might be associated with increased risk of renal progression in patients with IgA nephropathy.

Adolescent↗

Messenger RNA expression of RANTES in the urinary sediment of patients with lupus nephritis.

BACKGROUND: Lupus nephritis is characterized by intra-renal inflammation. Patients with systemic lupus erythematosus (SLE) showed abnormal T-cell expression of RANTES (regulated upon activation, normal T cell expressed) and its level in their serum. The authors studied the mRNA expression of RANTES in the urinary sediment of lupus patients. METHODS: The authors studied 88 lupus patients, who were classified into active, remission and non-renal SLE groups according to the disease activity, 29 non-SLE and 10 healthy controls. Lupus activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Urinary mRNA expression of RANTES was studied by real-time quantitative polymerase chain reaction. RESULTS: The expression of RANTES in urinary sediment was significantly elevated in active group (P < 0.001). Expression level of RANTES correlated with the SLEDAI score (r = 0.57; P < 0.001) and renal score in SLEDAI (r = 0.60; P < 0.001). In addition, urinary expression of RANTES had significant correlation with degree of proteinuria, serum creatinine, albumin and estimated glomerular filtration rate. CONCLUSION: The authors conclude that the mRNA expression of RANTES was elevated in the urinary sediment of patients with active lupus nephritis. Measurement of urinary mRNA expression may be a novel non-invasive method for the assessment of lupus disease activity and the severity of renal involvement.

Adult↗

The clinical course of peritoneal dialysis-related peritonitis caused by Corynebacterium species.

BACKGROUND: Corynebacterium species are part of the normal skin flora. The incidence of nosocomial infections caused by Corynebacterium species have increased substantially over the past two decades. However, the clinical course of Corynebacterium peritonitis complicating peritoneal dialysis remains unclear. METHOD: We reviewed all the Corynebacterium peritonitis in our dialysis unit from 1995 to 2002. During this period, there were 1485 episodes of peritonitis recorded; 27 (1.8%) of which were caused by Corynebacterium species. RESULTS: The underlying renal diagnosis and prevalence of comorbid conditions of the 27 patients were similar to our whole dialysis population. The bacteria isolated were resistant to penicillin in 8 cases (29.6%). Three cases (11.1%) had concomitant exit-site infection. The overall primary response rate was 74.1%; the complete cure rate was 37.0%. Episodes that received vancomycin as initial antibiotic had a marginally higher primary response rate (9 in 10 vs 11 in 17 episodes, P = 0.2) and complete cure rates (7 in 10 vs 3 in 17 episodes, P = 0.12) than the episodes that received cephalosporins, although neither of the differences was statistically significant. Thirteen cases (48.1%) had recurrent peritonitis after antibiotic therapy, 8 of which had the recurrent episode at least 30 days after stopping antibiotics (median 54 days, range 43-60 days). Eight recurrent cases (61.5%) were successfully cured by another 3 week course of intra-peritoneal vancomycin. CONCLUSIONS: Recurrent Corynebacterium peritonitis is common after a 2 week course of antibiotics. Recurrent Corynebacterium peritonitis may be delayed up to 2 months after the antibiotic is stopped. Recurrent peritonitis can usually be cured with a 3 week course of intra-peritoneal vancomycin, which is probably the preferred antibiotic regimen for Corynebacterium peritonitis.

Anti-Bacterial Agents↗

Impact of social factors on patients on peritoneal dialysis.

BACKGROUND: Clinical outcomes among patients on peritoneal dialysis (PD) might not be linked to medical factors alone. We studied the clinical impact of various social factors among patients on PD. METHODS: In a cohort of 102 consecutive patients who started PD in a single centre between 2003 and 2004, we evaluated the effects of social factors on the development of peritonitis and risk of hospitalization after initiation of PD. RESULTS: Of 102 incident PD patients, 35 subjects (34.3%) were referred to nephrologists more than 3 months before dialysis initiation. During 85.7 patient-years of observation (median follow-up, 10.7 months), four subjects died and six underwent kidney transplantation. Patients receiving social security assistance and those younger than 40 years fared worse than others in terms of their risk of peritonitis. Mean peritonitis-free time for subjects who were on social security assistance was 2.7 months, and for those who were not, 16.4 months (P = 0.045). In the Cox proportional hazards analysis, need for social security assistance and illiteracy were the only statistically significant factors associated with the time to a first peritonitis, after adjustment for social characteristics and relevant coexisting medical factors. Dependence on social security assistance prior to PD was associated with a >2-fold increased likelihood of peritonitis, with an adjusted risk ratio of 2.69 (95% confidence interval, 1.10 to 6.54; P = 0.029). The total number of hospitalization days was similar between those who received social security assistance and those who did not: 17.4+/-14.6 days (range, 4-50 days) vs 17.9+/-14.0 days (range, 0-60 days) (P = 0.89). CONCLUSIONS: Our results confirm that socioeconomic status is closely associated with the rate of peritonitis among PD patients. The long-term reliability of these social predictors remains to be validated.

Adult↗

Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients.

BACKGROUND: Fetuin-A (alpha2-Heremans Schmid glycoprotein) has recently been identified as a circulating inhibitor of calcification and is regulated as a negative acute phase protein. However, its relationships with cardiac valvular calcification and atherosclerosis and outcome have not been evaluated in peritoneal dialysis (PD) patients. METHOD: We performed a prospective follow-up study in 238 PD patients with echocardiography done at baseline to detect cardiac valvular calcification and biochemical analysis performed for serum fetuin-A, albumin and C-reactive protein (CRP). RESULTS: Baseline serum fetuin-A concentration was (mean+/-SD) 0.309+/-0.068 g/l (normal range 0.4-0.95). Across the three tertiles of increasing serum fetuin-A, a significant trend effect was observed for age (P = 0.023), diabetes (P = 0.008), background atherosclerotic vascular disease (P = 0.010), cardiac valvular calcification (P = 0.002), serum albumin (P<0.001), subjective global assessment (P = 0.005) and CRP (P<0.001). Adjusting for CRP and calcium x phosphorus product, every 0.01 g/l increase in serum fetuin-A remained independently associated with a 6% decrease in the risk of valvular calcification (95% confidence intervals, 0.90-0.99; P = 0.028). Furthermore, serum fetuin-A showed a significant decrease across the four groups of patients with increasing components of the malnutrition, inflammation, atherosclerosis/calcification (MIAC) syndrome (P<0.001) and was the lowest among patients with all components of the MIAC syndrome (0.263+/-0.055 g/l) and highest among those who do not have the MIAC syndrome at all (0.338+/-0.063 g/l). Lower serum fetuin-A was associated with greater all-cause mortality (P = 0.0011) and fatal and non-fatal cardiovascular events (P = 0.0017), but its significance was lost when atherosclerotic vascular disease, valvular calcification, inflammation and malnutrition were included in the model. CONCLUSIONS: Serum fetuin-A showed important associations with valvular calcification, atherosclerosis, malnutrition and inflammation, and was linked to mortality and cardiovascular events in PD patients via its close relationships with the MIAC syndrome.

Arteriosclerosis↗

Cardiac valvular calcification as a marker of atherosclerosis and arterial calcification in end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk for tissue calcifications as a result of deranged mineral metabolism. We tested the hypothesis that valvular calcification is a marker of atherosclerosis in patients with ESRD. METHODS: Echocardiography was performed in 92 patients undergoing peritoneal dialysis with no background atherosclerotic vascular complications to detect valvular calcification. We used B-mode ultrasonography to determine carotid artery intima-media thickness and the presence of plaque and calcification. RESULTS: Compared with patients without valvular calcification (n=66), those with valvular calcification (n=26) had higher C-reactive protein levels (P=.01) and greater mean +/- SE carotid intima-media thickness (1.12 +/- 0.06 vs 0.88 +/- 0.04 mm; P=.003). Carotid artery calcification was present unilaterally and bilaterally in 4 patients (15%) and 17 patients (65%) with valvular calcification vs 11 (17%) and 14 (21%) without, respectively (P<.001). Carotid artery plaque was present unilaterally and bilaterally in 11 patients (12%) and 16 patients (65%) with valvular calcification vs 3 (17%) and 17 (24%) without, respectively (P=.001). Using multiple logistic regression analysis, every 1-mm increase in carotid intima-media thickness was independently associated with a 6.51-fold (95% confidence interval, 1.58-26.73; P=.009) increased risk of valvular calcification, and calcification and plaque in the carotid arteries were associated with a 7.18-fold (95% confidence interval, 2.39-21.51; P<.001) and a 5.00-fold (95% confidence interval, 1.77-14.13; P=.002) increased risk of valvular calcification, respectively. CONCLUSION: The associations among valvular calcification, inflammation, carotid atherosclerosis, and arterial calcification suggest that valvular calcification is a marker of atherosclerosis and arterial calcification in patients with ESRD.

Analysis of Variance↗

Differential effects of transforming growth factor-beta on the synthesis of connective tissue growth factor and vascular endothelial growth factor by peritoneal mesothelial cell.

BACKGROUND: Previous studies found that transforming growth factor-beta (TGF-beta) plays a conflicting role in peritoneal fibrosis. We hypothesise that TGF-beta acts on peritoneal mesothelial cells (PMC) via VEGF and CTGF as downstream mediators. METHODS: The effect of TGF-beta in primary culture of rat PMC was studied. VEGF and CTGF mRNA expression was examined by real time quantitative polymerase chain reaction (RT-QPCR), and VEGF antigen level in cell supernatant by ELISA. RESULTS: Incubation of rat PMC with TGF-beta resulted in a time- (3-72 h) and concentration- (0-50 pg/ml) dependent increase in VEGF mRNA expression, and VEGF protein level in the cell supernatant. When stimulated with TGF-beta 100 pg/ml, there was a 20-fold up-regulation of VEGF mRNA expression (p < 0.001). The CTGF mRNA expression and protein level of PMC was slightly increased at low concentration of TGF-beta (50 pg/ml) but decreased at a higher concentration (100 pg/ml or above). The effect of TGF-beta on PMC CTGF, but not VEGF, gene expression was inhibited by Smad decoy oligodeoxynucleotide. The effect of TGF-beta on PMC VEGF gene expression and protein synthesis was inhibited by PD98059 (a specific MAP kinase inhibitor) and chelerythrine (a specific protein kinase C inhibitor), but not cholera toxin (activator of cyclic AMP) or herbimycin A (inhibitor of protein tyrosine kinase). The up-regulation of CTGF mRNA expression was inhibited by PD98059, but not chelerythrine, cholera toxin or herbimycin A. Furthermore, CTGF gene expression in TGF-beta-stimulated PMC was inhibited by co-administration of recombinant VEGF. CONCLUSIONS: Our data demonstrate that TGF-beta induces PMC production of VEGF and CTGF via different signalling pathways. At high concentration of TGF-beta, VEGF production predominates and CTGF production was inhibited. Since CTGF and VEGF have different biologic effects, our results may explain the complex activity of TGF-beta in peritoneal physiology.

Animals↗

Pharmacokinetic advantages of two-hour post-dose cyclosporin a level for the therapeutic drug monitoring in stable Chinese kidney transplant recipients.

BACKGROUND: Recent studies in Caucasian patients show that 2-hour post-dose cyclosporin A level (C2) monitoring has excellent correlation with the actual drug exposure and risk of rejection. However, the reliability of using C2 in stable Chinese renal transplant patients is unknown. METHODS: Forty-nine stable Chinese renal transplant patients receiving microemulsion cyclosporin A (Neoral) as part of their immunosuppressive therapy were recruited. Area under the time-concentration curve (AUC) was determined from whole blood cyclosporin A level taken at 0, 1, 2, 4 and 6 h post-dose at time 0 month. Cyclosporin A levels were repeated at 0, 1 and 2 h post-dose at 1 and 2 months later to determine the intra-individual variation at these specific time points. RESULTS: The average duration of transplantation was 77 +/- 42 months, with average daily cyclosporin dosage of 200 +/- 43 mg in two divided doses. AUC has excellent correlations with cyclosporin A level at 1 h (C1) and 2 h (C2) (r = 0.81 and 0.82 respectively, p < 0.001 for both). The correlation between AUC and trough cyclosporin A level (C0) was statistically significant but only modest (r = 0.52, p < 0.001). On the other hand, the intra-individual coefficient of variation (CVw) of C1 was significantly larger than that of C2 (34.4 +/- 24.2 vs. 15.9 +/- 8.3%, p < 0.0001). CONCLUSION: We conclude that C2 level has favorable pharmacokinetic properties for therapeutic drug monitoring in stable Chinese transplant recipients. Both C1 and C2 have excellent correlation with AUC, but the intra-individual variability of C2 is much lower than that of C1.

Aged↗

Messenger RNA expression of glomerular podocyte markers in the urinary sediment of acquired proteinuric diseases.

BACKGROUND: Podocyte slit diaphragm plays an important role in the control of glomerular permeability. We hypothesize that studying the gene expression profile of podocyte in urinary sediment may provide diagnostic and prognostic information on acquired proteinuric diseases. METHODS: We studied 28 patients who required kidney biopsy for acquired proteinuric diseases (diabetic glomerulosclerosis, 9 cases; IgA nephropathy, 10 cases; minimal change disease, 5 cases; membranous nephropathy, 5 cases). We also studied 10 cases of diabetic microalbuminuria and 9 healthy controls. The mRNA expressions of nephrin (NephRNA), podocin (PodRNA) and synaptopodin (SynRNA) in urinary sediment were measured by real time quantitative PCR. After recruitment, all patients were followed for at least 12 months. RESULTS: There were significant differences in the NephRNA and PodRNA in the urinary sediment between diagnosis groups (p<0.005). On the other hand, SynRNA was only marginally significant between diagnosis groups (p<0.05). Although statistically significant, the degree of proteinuria had only modest correlations with the urinary expression of nephrin. After a median follow up for 23 months, there was a significant correlation between the rate of decline in renal function and NephRNA (r=0.559, p=0.001) and PodRNA (r=0.530, p=0.002), but not SynRNA (r=0.054, p=NS). The correlation remained statistically significant after multivariate analysis to adjust for the degree of proteinuria and initial renal function. CONCLUSIONS: Urinary mRNA expression of podocyte markers, such as nephrin and podocin, are significantly different between proteinuric disease categories. Further, NephRNA and PodRNA correlated with the rate of decline in renal function. Our results suggest that urinary podocyte gene expression may be a useful non-invasive tool which provides additional information for the management of proteinuric diseases.

Adult↗

Circulating soluble vascular cell adhesion molecule 1: relationships with residual renal function, cardiac hypertrophy, and outcome of peritoneal dialysis patients.

BACKGROUND: Vascular cell adhesion molecule 1 (VCAM-1) is involved in leukocyte-endothelial cell interaction and has a pivotal role in inflammation. Whether it contributes to excessive mortality in dialysis patients remains uncertain. In this study, we examined circulating soluble VCAM-1 (sVCAM-1) in relation to different clinical and biochemical parameters, as well as mortality and cardiovascular events, in peritoneal dialysis (PD) patients. METHODS: Values for serum sVCAM-1, together with C-reactive protein (CRP), homocysteine, albumin, lipid profile, blood hemoglobin, and indices of dialysis adequacy, were determined at study baseline, and echocardiography was performed in 160 long-term PD patients. Patients were followed up for a mean of 35 +/- 16 (SD) months. RESULTS: Serum sVCAM-1 levels were elevated in our continuous ambulatory PD (CAPD) patients and showed a negative correlation with residual glomerular filtration rate (GFR; P < 0.001) and low-density lipoprotein (LDL) cholesterol level (P = 0.004), but a positive correlation with left ventricular mass index (P = 0.025). Using Kaplan-Meier analysis, overall survival rates at 2 years were 96.2%, 75.2%, and 50.6% for patients in the lower, middle, and upper tertiles of sVCAM-1 levels, respectively (P < 0.0001). Fatal and nonfatal cardiovascular event-free survival rates were 58.2%, 56.9%, and 19.4% for patients in the lower, middle, and upper tertiles, respectively (P < 0.0001). Using Cox regression analysis with adjustment for confounding covariates, every 100-ng/mL increase in sVCAM-1 level was associated with 8% (95% confidence interval, 1.03 to 1.13) and 5% (95% confidence interval, 1.00 to 1.10) increases in risk for death and fatal and nonfatal cardiovascular events, respectively. Its significance for all-cause mortality remained with additional adjusting for LDL cholesterol level, but was lost when adjusting for residual GFR. Its association with cardiovascular events became insignificant when adjusting for LDL cholesterol level or residual GFR. Furthermore, patients with both sVCAM-1 and CRP levels elevated at the 50th percentile or greater were associated with the greatest death and fatal and nonfatal cardiovascular event rates compared with those with either CRP or sVCAM-1 level elevated at the 50th percentile or greater. CONCLUSION: Circulating sVCAM-1 levels show an important link with residual renal function, LDL cholesterol level, and cardiac hypertrophy in CAPD patients. Furthermore, residual renal function, which correlates inversely with circulating sVCAM-1 level, shows an important association with all-cause mortality and cardiovascular events and displaces sVCAM-1 level from the models for all-cause mortality and future cardiovascular events in CAPD patients. Additional study is needed to explore possible mechanistic links between inflammation, soluble adhesion molecules, residual renal function, and cardiac hypertrophy in CAPD patients.

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