Biomedical subjects

Daqing Guo

Publications and source records attributed to Daqing Guo.

8 recordsLinked to original sources

PubMed2005

Plasma interleukin-6 predicts cardiovascular mortality in hemodialysis patients.

BACKGROUND: Interleukin-6 (IL-6) is a mediator and marker of the chronic inflammatory process that is responsible for much of the morbidity and mortality seen in hemodialysis (HD) patients. This study evaluated circulating plasma IL-6 as a predictor of all-cause mortality and cardiovascular mortality and studied its relationship to prevalent comorbidity and hypoalbuminemia, in a cohort of stable HD patients enrolled in the HEMO study. METHODS: Clinical data included demographic, medical, and routine laboratory parameters. Comorbidities were graded using the Index of Co-Existing Diseases (ICED). Outcomes of interest were all-cause mortality and cardiovascular mortality. Blood samples were drawn at enrollment and annually, and plasma IL-6 levels measured with high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Median plasma IL-6 level in 206 patients was 7.9 pg/mL (range, 0.1 to 90.3 pg/mL) and was higher in patients with vascular disease ( P = 0.03), higher ICED scores ( P = 0.01), and lower Karnofsky indices ( P < 0.01). Serum albumin was inversely related to plasma IL-6 levels ( P = 0.03, r = -0.16). Unadjusted median survival time was 1,209 days in the lowest quartile of plasma IL-6 and 806 days in the highest ( P = 0.02, log rank test). A 1-log increase in plasma IL-6 was associated with a 1.19-fold higher adjusted risk for all-cause mortality ( P = 0.04; 95% confidence interval, 1.01 to 1.40) and a 1.43-fold higher adjusted risk of cardiovascular mortality ( P = 0.02; 95% confidence interval, 1.06 to 1.92). Hazard ratio estimates were higher when IL-6 levels over time were incorporated as a time-dependent covariate. CONCLUSION: Plasma IL-6 levels are strongly associated with comorbidity in HD patients and are a powerful predictor of cardiovascular and all-cause mortality.

Adolescent↗

PubMed2004

Cytokine gene promoter polymorphisms and mortality in acute renal failure.

BACKGROUND: Although cytokines play a pivotal role in the inflammatory responses that mediate the severity of acute renal failure (ARF), the importance of pro- and anti-inflammatory cytokine gene promoter polymorphisms has been unexplored. METHODS: We prospectively evaluated the relationship of single nucleotide polymorphism in the promoter region of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) to mortality in 61 patients with ARF requiring intermittent hemodialysis. Cytokine genotyping was performed on leukocytes using PCR techniques. Cox proportional-hazards regression analysis was used to explore these relationships. RESULTS: The mean (+/-SD) APACHE II score was 24 +/- 7, MOF score 2 +/- 1, and 64% had sepsis. The TNF-alpha high producer genotype (-308 A-allele carrier) was associated with a higher risk of death after adjustment for the APACHE II score (HR=2.5; P=0.04), and the IL-10 intermediate/high producer genotype (-1082 G-allele carrier) was associated with a lower risk of death after adjustment for the MOF score (HR=0.36; P=0.03). Considering combinations of genotypes, the TNF-alpha high and IL-10 low producer genotype combination was associated with a approximately 6-fold increased risk of death compared to the TNF-alpha-low and IL-10 intermediate/high producer genotype combination, after adjustment for either APACHE II (P=0.004), MOF score (P=0.004) or sepsis (P=0.006). CONCLUSIONS: TNF-alpha and IL-10 gene polymorphisms are related to the risk of death among patients with ARF who require dialysis. Larger studies are needed to confirm these relationships.

Acute Kidney Injury↗

PubMed2004

Dialyzer membrane type and reuse practice influence polymorphonuclear leukocyte function in hemodialysis patients.

BACKGROUND: Polymorphonuclear leukocyte (PMNL) production of reactive oxygen species (ROS) has been linked to hemodialysis (HD) associated morbidity. The effect of dialyzer membrane type and reuse on PMNL function has not been clearly defined. METHODS: The present report is a cross-sectional study undertaken in a cohort of patients undergoing regular HD, at enrollment into the Hemodialysis (HEMO) Study, to study the association between patient and dialysis-related factors and PMNL function. PMNL function was assessed by measuring PMA- and N-formyl methionyl-leucyl-phenylalanine (fMLP) -induced respiratory burst, and phagocytic activity toward Staphylococcus aureus. RESULTS: PMNL from patients dialyzed with polysulphone (PS) or cuprophane (CU) membranes showed higher PMA-induced respiratory burst activity compared with those exposed to substituted cellulose (cellulose acetate, cellulose triacetate, CA/CT) membranes, regardless of dialyzer reuse. The use of bleach as a cleansing agent during reuse was associated with higher PMA-induced PMNL superoxide production, as was the use of renalin when compared to aldehydes. In a subgroup of patients using PS dialyzers, reuse itself was associated with higher fMLP-induced superoxide production. The type of bleach-germicide combination during reuse showed that use of renalin as a germicide was also associated with higher PMNL phagocytosis index. The number of years on HD correlated inversely with PMA-induced PMNL superoxide response. Weaker PMNL response to fMLP was associated with greater comorbidity and poor functional status as quantified by Index of Coexisting Diseases (ICED) and Karnofsky scores, respectively. CONCLUSION: Our results indicate that dialyzer membrane type and the reuse process influence the oxidative response of PMNL among HD patients. The implications of these observations on clinical morbidity need to be further evaluated in prospective studies.

Aged↗

PubMed2004

Cytokine gene polymorphisms in hemodialysis patients: association with comorbidity, functionality, and serum albumin.

BACKGROUND: Cytokine-orchestrated chronic inflammation plays a major role in long-term morbidity and mortality in patients with end-stage renal disease (ESRD) on hemodialysis (HD). In this cross-sectional study, we evaluated the association between specific alleles/genotypes and combinations of genotypes of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-10 with indices of comorbidity, functional status, and other biological markers in a cohort of 183 ESRD patients recruited to the Hemodialysis (HEMO) Study from two Boston centers. METHODS: Genotyping was performed for single nucleotide polymorphisms in the promoter region of IL-6 (-174 G-->C), TNF-alpha (-308 G-->A), and IL-10 (-1082 G-->A). The relationship of specific genotypes to the index of coexistent disease (ICED) score (an index of comorbidity), Karnofsky Index (a measure of functional status), serum albumin, and nutritional indices (anthropometric measurements, body mass index, normalized protein catabolic ratio) were studied. Plasma IL-6 levels, as well as TNF-alpha and IL-10 production by endotoxin-stimulated peripheral blood mononuclear cells (PBMC), were also measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with the high producer genotypes for the proinflammatory cytokines IL-6 (G/G and G/C) and TNF-alpha (G/A and A/A) had significantly higher comorbidity (ICED scores of > or =2) and lower functional scores (Karnofsky Index) compared with patients with the low producer genotypes for these cytokines (C/C and G/G, respectively). In contrast, patients with the high and intermediate producer genotypes (G/G and G/A) for the anti-inflammatory cytokine IL-10 had a higher Karnofsky Index compared with those with the low producer genotype (A/A). Serum albumin levels were lower in patients with the TNF-alpha high producer genotype (G/A and A/A) compared with those with the low producer genotype (G/A and A/A). On multivariate analysis, the IL-6 high producer genotypes were associated with an odds ratio (OR) of 4.87 for higher comorbidity (ICED scores > or =2) (P= 0.02), and 4.9 for lower Karnofsky Index (lower functional status) (P= 0.04) compared with patients with the low IL-6 producer genotypes. Similarly, the TNF-alpha high producer genotype was associated with increased odds for a higher ICED score, lower Karnofsky Index, and lower serum albumin compared with patients with the low producer genotype for this cytokine. In contrast, the IL-10 high/intermediate producer genotype was associated with increased odds for a higher Karnofsky Index (P= 0.05). Cytokine genotype combinations-the TNF-alpha high producer and IL-6 high producer genotype combination, and the IL-6 high producer and IL-10 low producer genotype combination-were independently associated with a higher ICED score. These genotype combinations, as well as the TNF-alpha high producer and IL-10 low producer genotype combination, were also associated with a lower Karnofsky Index. CONCLUSION: In ESRD patients on long-term HD, single nucleotide polymorphisms in the promoter region of the proinflammatory cytokines IL-6 and TNF-alpha, and the regulatory monokine IL-10, show a strong association with indices of comorbidity and function, and biological and nutritional markers.

Aged↗

PubMed2004

Transforming growth factor-beta 1 gene polymorphisms and cardiovascular disease in hemodialysis patients.

BACKGROUND: Atherosclerotic vascular disease is a leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that inhibits the atheromatous process. We studied coding region polymorphisms of the TGF-beta1 gene (+869 T --> C at codon 10 and +915 G --> C at codon 25) as genetic susceptibility factors for prevalent vascular disease and cardiac outcomes in a cohort of HD patients enrolled in the HEMO Study. METHODS: Genotyping was carried out using polymerase chain reaction-sequence specific primer (PCR-SSP) methods with a cytokine genotyping tray. Prevalent vascular disease was coded from the Index of Disease Severity (IDS) scores for ischemic heart disease (IHD), peripheral vascular disease (PVD), cerebrovascular disease (CVD), and congestive heart failure (CHF), 0 indicating absence, and 1 to 3 increasing grades of severity. The presence of any vascular disease (VD) (i.e., any degree of IHD/PVD/CVD), and the number of coexistent vascular system diseases per patient were derived. Cardiac outcomes, one of the secondary outcomes of the HEMO Study, were expressed as a composite of the first hospitalization for, or death from, cardiac causes. RESULTS: The cohort consisted of 183 patients at enrollment, 56% male, 44% African American (AA), and 40% diabetic. The mean age was 62.4 +/- 12.2 years, and median dialysis vintage 2.02 years. The most frequent genotype at codon 10 was T/C (67%), and at codon 25 was G/G (72%). IHD was present in 52% of patients; 65% had at least one vascular system involvement, and 31% had 2 or more. On both univariate and multivariate analysis, the G/C genotype at codon 25 was significantly associated with the presence and extent of vascular disease at enrollment. The median time to cardiac outcome, defined as a composite of the first hospitalization for, or death from, cardiac causes, was 411 days in patients with the G/C genotype compared with 851 days in those with the G/G genotype (P= 0.03). Patients with the G/C genotype had a 1.6-fold increased hazard for cardiac outcomes after adjustment for baseline covariates (P= 0.04). CONCLUSION: The G/C substitution at codon 25 was associated with an increased risk for prevalent vascular disease, new onset cardiac morbidity, and cardiac mortality in HD patients, and may be a genetic susceptibility factor for the development of atherosclerosis. Further studies are required to evaluate the role of TGF-beta1 as a candidate gene.

Aged↗

PubMed2004

Reprocessed (high-flux) Polyflux dialyzers resist trans-membrane endotoxin passage and attenuate inflammatory markers.

BACKGROUND: Bacterial contamination of dialysis water can contribute to the chronic microinflammatory state observed in dialysis patients. This study characterized the selective permeability of new and peroxyacetic acid/acetic acid/hydrogen peroxide (Renalin) reprocessed high-flux, polyarylethersulfone-polyvinylpyrrolidone (Polyflux-17R) dialyzers after exposure to endotoxin-contaminated dialysate during in vitro dialysis. Clinical correlation with pre-dialysis levels of systemic markers of inflammation, and clearance of middle molecules was also assessed in vivo. METHODS: Six hemodialysis (HD) patients were enrolled in the study. After reuses 0, 1, 5, 10, and 15, the dialyzers were reclaimed and submitted to an in vitro dialysis circuit using standard dialysate and blood from healthy volunteers. New and reprocessed dialyzers were sequentially exposed to escalating doses of Pseudomonas aeruginosa endotoxin in the dialysate compartment, and whole blood tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production was used as an index of reverse passage of endotoxin. In vivo, IL-6, C-reactive protein (CRP) and serum amyloid A (SAA) levels were measured to assess the impact of reprocessing on the systemic inflammatory response. Finally, pre- and post-dialysis samples were collected to measure urea and beta(2)-microglobulin (beta(2)-M) clearances. RESULTS: During in vitro dialysis, blood-side endotoxin levels were undetectable following dialysate contamination. TNF-alpha production remained unchanged (p = NS), and IL-6 production fell significantly on reuses 0, 1, 10, and 15 (p = 0.03) suggesting membrane adsorption, as a result of reuse-dependent surface binding. In vivo, whereas IL-6 and SAA levels did not significantly differ (p = 0.90 and 0.59, respectively), CRP levels fell near significantly, over the course of 15 reuses (p = 0.06). In vivo, beta(2)-M clearance was not affected by the reuse technique (p = 0.28). CONCLUSIONS: This study provides in vitro and in vivo evidence arguing that high-flux Polyflux dialyzers provide more than adequate dialysis, while preventing the in vitro back-diffusion of bacterial endotoxin despite 15 reuses with Renalin. Clinically, this may translate into an attenuation of the microinflammatory milieu.

Aged↗

PubMed2003

Effect of a novel adsorbent on cytokine responsiveness to uremic plasma.

BACKGROUND: Middle molecules such as beta2-microglobulin (beta2M) and advanced glycation end products (AGE)-modified proteins contribute to inflammation in uremia. The BetaSorb column is a new adsorptive device, which contains copolymeric beads, suitable for removal of beta2M and other middle molecules. We assessed the effect of this column on the bioreactivity of uremic plasma, as measured by cytokine responsiveness. METHODS: Uremic plasma was perfused in vitro through the column (10 mL/min) and samples were collected after 10 to 30 passes. Endotoxin-stimulated tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) production by THP-1-derived monocytes was measured following brief exposure to uremic plasma. beta2M levels were measured. The contribution of AGE-modified proteins to the bioreactivity of uremic plasma was explored. RESULTS: TNF-alpha and IL-10 production markedly decreased after 30 passes (629 +/- 78 vs. 144 +/- 62 pg/mL; 207 +/- 25 vs. 117 +/- 23 pg/mL; P=0.04). The column removed beta2M efficiently with a marked decline in plasma levels by 99% after 30 passes. Neutralization of AGE receptor (RAGE) resulted in a further reduction in the bioreactivity of uremic plasma. This was observed with nonperfused, as well as perfused, uremic plasma, suggesting that AGE-modified proteins were biologically active and still present after perfusion. CONCLUSION: The sorbent beads removed uremic solute(s) that prime monocytes to enhanced cytokine production. Removal of beta2M was efficient, and of native and AGE-modified middle molecules likely.

Antibodies↗

PubMed2002

Defective interleukin-10 synthesis by peripheral blood mononuclear cells among hemodialysis patients.

BACKGROUND: Interleukin-10 (IL-10), a potent regulatory monokine produced by activated mononuclear cells, provides an efficient autocrine mechanism for controlling proinflammatory cytokine synthesis. We hypothesized that defective synthesis of IL-10 could contribute to the inflammatory state in hemodialysis (HD) patients due to impaired feedback inhibition of proinflammatory cytokine production. METHODS: We compared peripheral blood mononuclear cell (PBMC) synthesis and transcription of IL-10 and TNF-alpha in 12 patients with end-stage renal disease on long-term maintenance HD and a control group of 10 healthy subjects. RESULTS: The synthesis of IL-10 by unstimulated PBMC was detectable in 5 of 12 (42%) HD patients as compared to 7 of 10 (70%) controls (p = 0.02). IL-10 synthesis in response to endotoxin (ET) by PBMC from HD patients was significantly lower when compared to the robust response in the control group (p = 0.008). Among the HD patients, there was a positive correlation between ET-stimulated IL-10 synthesis and the duration of time on dialysis. Unstimulated and ET-stimulated synthesis of TNF-alpha by PBMC did not differ between the 2 groups. In the HD patients, there was an inverse correlation between TNF-alpha and IL-10 synthesis by ET-stimulated PBMC, suggesting a regulatory effect of IL-10 on PBMC TNF-alpha synthesis. There was also an inverse correlation between plasma albumin and ET-stimulated TNF-alpha synthesis by PBMC among HD patients. TNF-alpha mRNA expression did not differ in HD patients relative to healthy controls. In contrast, when IL-10 mRNA from ET-stimulated PBMC was quantified, there was marked difference between the 2 groups indicating a transcriptional defect in IL-10 synthesis in PBMC from HD patients. CONCLUSION: Our observations indicate a marked abnormality in IL-10 synthesis by PBMC from HD patients probably related to a transcriptional defect. Low PBMC IL-10 synthesis may contribute to a chronic inflammatory state in these patients by defective feedback inhibition of proinflammatory cytokine production.

Adult↗