Biomedical subjects

Orfeas Liangos

Publications and source records attributed to Orfeas Liangos.

16 recordsLinked to original sources

PubMed2006

NADPH oxidase p22phox and catalase gene variants are associated with biomarkers of oxidative stress and adverse outcomes in acute renal failure.

Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro- and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position +242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position -262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity. Genomic DNA was extracted from peripheral blood leukocytes and analyzed with a restriction fragment length polymorphism PCR method. Genotype-phenotype associations were characterized by measuring circulating nitrotyrosine and catalase activity. Observed and expected genotype frequencies were not significantly different, and overall baseline characteristics were not significantly different according to the various genotype groups. A genotype-phenotype association was demonstrable between the NADPH oxidase p22phox genotypes and plasma nitrotyrosine level (P = 0.06), as well as between the catalase genotypes and whole-blood catalase activity (P < 0.001). Compared with the NADPH oxidase p22phox CC genotype group, the T-allele group had a higher cumulative probability of remaining hospitalized (P = 0.03). Compared with the NADPH oxidase p22phox CC genotype, the T-allele carrier state was associated with 2.1-fold higher odds for dialysis requirement or hospital death (P = 0.01). This association persisted with 2.0- to 2.2-fold higher odds for this composite outcome after adjustment for race; gender; age; and the Acute Physiology and Chronic Health Evaluation II score (P = 0.03), the Multiple Organ Failure score (P = 0.01), or presence of sepsis (P = 0.02). The polymorphism in the gene that encodes the NADPH oxidase p22phox subunit at position +242 is associated with dialysis requirement or hospital death among patients with ARF. Larger studies are needed to confirm these relationships.

Acute Kidney Injury↗

PubMed2006

A systematic review of the effect of the Excebrane dialyser on biomarkers of lipid peroxidation.

BACKGROUND: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anaemia. We conducted a systematic review and meta-analysis to examine the effect of Excebrane, a vitamin E-coated cellulose-based dialyser, on circulating biomarkers of lipid peroxidation, as surrogate markers of oxidative stress. METHODS: The primary sources used to identify candidate studies included PubMed, the Cochrane Central Register of Controlled Trials, a bibliography provided by the dialyser manufacturer, and a manual search of abstracts from proceedings of scientific meetings and review articles. Studies were selected for analysis if their design included a comparator group (primarily within patient comparison, i.e. pre- and post-study evaluations). For the meta-analysis, we computed the overall change of the outcome from baseline using a random-effects model. A supplemental analysis was performed in which the absolute levels of these biomarkers of lipid peroxidation were converted to a common unit by calculating standardized effect sizes. RESULTS: Fourteen peer-reviewed articles met the criteria. The studies consisted of 11 single arm, one randomized crossover and two randomized controlled trials, with a total of 37 to 158 evaluable patients, according to the outcome of interest analysed. Due to the paucity of randomized trials, the meta-analysis was limited to the Excebrane arm of each study. When the studies were combined according to similar measurement units, the overall mean decrease in malondialdehyde (MDA) level was -0.3 mM (95% CI, -0.5 to -0.1 mM; seven studies) and -0.8 nmol/mg low-density lipoprotein (LDL) (95% CI, -1.3 to -0.4 nmol/mg LDL; three studies), respectively. The summary estimate revealed a non-significant decrease in pre-dialysis thiobarbituric acid reactive substances (TBARS) level of 0.4 microM (95% CI, -1.2 to 0.4 microM; three studies). When the MDA and TBARS studies were combined using the standardized effect size, the mean decrease in these biomarkers of lipid peroxidation was statistically significant at -1.7 units (95% CI, -2.7, -0.7 units; 13 studies). A meta-analysis on the effect of Excebrane on pre-dialysis levels of oxidized-LDL could not be performed due to study heterogeneity. CONCLUSION: The conversion of dialysis patients to a vitamin E-coated dialyser is associated with an improvement in circulating biomarkers of lipid peroxidation, which is of potential clinical benefit.

Antioxidants↗

PubMed2006

Validity of International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Acute Renal Failure.

Administrative and claims databases may be useful for the study of acute renal failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the corresponding diagnosis and procedure codes is unknown. The performance characteristics of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for ARF were assessed against serum creatinine-based definitions of ARF in 97,705 adult discharges from three Boston hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical records in 150 patients with ARF-D and 150 control patients. As compared with a diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of 47.9%, and negative predictive value of 96.1%. As compared with review of medical records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and negative predictive value of 90.0%. It is concluded that administrative databases may be a powerful tool for the study of ARF, although the low sensitivity of ARF codes is an important caveat. The excellent performance characteristics of ICD-9-CM codes for ARF-D suggest that administrative data sets may be particularly well suited for research endeavors that involve patients with ARF-D.

Acute Kidney Injury↗

PubMed2006

Acute renal failure after endovascular vs open repair of abdominal aortic aneurysm.

OBJECTIVE: Endovascular aneurysm repair (EVAR) is an increasingly used alternative to open surgical repair of unruptured abdominal aortic aneurysms (AAAs). The effect of EVAR on postprocedure acute renal failure has not been determined. We hypothesized that EVAR would be associated with a lower risk of acute renal failure and acute renal failure requiring hemodialysis. METHODS: A retrospective cohort study was conducted of the 2002 Nationwide Inpatient Sample, the largest all-payer inpatient care database in the United States, reflecting discharges from a representative sample of United States hospitals. We identified 6614 discharges with a primary diagnosis of unruptured AAA and a primary procedure code for open AAA repair or EVAR. We excluded 56 patients with end-stage renal disease and 42 patients who underwent concomitant aortorenal bypass. We compared EVAR vs open repair in this cohort. The main outcome measures were acute renal failure and acute renal failure requiring dialysis. RESULTS: A total of 6516 patient discharges met the inclusion criteria for the study, and postprocedure acute renal failure developed in 439 (6.7%). EVAR was associated with lower odds of acute renal failure (adjusted odds ratio, 0.42; 95% confidence interval, 0.33 to 0.53) and acute renal failure requiring dialysis (adjusted odds ratio, 0.30, 95% confidence interval, 0.15 to 0.63). Results were similar when EVAR and open AAA repair were compared within quintiles of the propensity score for the receipt of EVAR. CONCLUSIONS: Compared with open AAA repair, EVAR is associated with a lower risk of postprocedure acute renal failure.

Acute Kidney Injury↗

PubMed2004

Relationship of urine output to dialysis initiation and mortality in acute renal failure.

BACKGROUND: A non-oliguric state is considered a good prognostic indicator in acute renal failure (ARF), and may lead to withholding renal replacement therapy in anticipation of recovery. The present study explores the relationship between urine volume and the start of dialysis and hospital mortality in patients with ARF. METHODS: In a non-concurrent cohort of patients with ARF treated exclusively with intermittent hemodialysis (IHD), demographic, clinical and laboratory characteristics were collected at the time of the first nephrology consultation and at the start of dialysis. Multiple linear and logistic regression analyses were used to identify factors associated with the time to initiation of dialysis and hospital mortality, respectively. RESULTS: Urine volume correlated with the time from admission to start of dialysis (r = 0.60; p < 0.001). Higher urine volume, lower serum creatinine and lower APACHE II score were independently associated with increased time from admission to start of dialysis. Hospital mortality was independently associated with a higher urine volume (odds ratio, OR 3.8, 95% confidence interval, CI, 1.1-12.8, p = 0.03), a higher MOF score (OR 4.9, 95% CI 1.1-21.6, p = 0.03) and a higher number of dialysis treatments performed in the 1st week (OR 3.7, 95% CI 1.2-11.3, p = 0.03). CONCLUSIONS: Among patients with ARF requiring IHD, increased urine output is associated with higher mortality. This observation may reflect physician bias toward later initiation of dialysis in non-oliguric ARF. Further research is needed to help identify patients with non-oliguric ARF who require early dialytic support.

Acute Kidney Injury↗

PubMed2004

Factors associated with urea reduction ratio in acute renal failure.

Prescription and delivery of hemodialysis (HD) in acute renal failure (ARF) may be affected by patient-related factors such as hemodynamic instability, catabolism, variable extracellular fluid volume, and coagulation disturbances. This study was undertaken in a cohort of patients with ARF requiring HD, to quantify patient- and dialysis-related variables that influence dialysis delivery. The urea reduction ratio (URR) was calculated for each HD session. Patient-related variables included age, gender, weight, mean arterial pressure, and Acute Physiological and Chronic Health Evaluation (APACHE) II and Multiple Organ Failure (MOF) scores. Dialysis-related variables were dialyzer characteristics (membrane type, surface area, KoA, and K(UF)), blood flow rate (Qb), session length, anticoagulant use, vascular access, and ultrafiltration volume. The analysis of factors associated with URR was performed using mixed linear statistical models. The cohort consisted of 81 adult patients with ARF who underwent 419 consecutive dialysis sessions. Mean (+/- SD) age was 60 +/- 18 years; 57% were male. At dialysis initiation, APACHE II score was 23 +/- 8 and MOF score 2 +/- 1. The number of HD treatments averaged 5.5 +/- 6.1/patient and 0.8 +/- 0.2/patient/day, mean URR was 54 +/- 15%, and session length 3.2 +/- 1.1 h; 58% used a femoral venous catheter, and 92% polysulfone dialyzers. Among patient-related variables, the only independent predictor of delivered dose of dialysis, as measured by URR was the predialysis weight (P < 0.01). Among the dialysis-related variables, treatment time (P < 0.01), dialyzer surface area (P < 0.01), dialyzer K(UF) (P = 0.04), blood flow rate (P < 0.01), and the use of a femoral venous catheter (P < 0.01) were also independently associated with URR. An interaction between vascular access site and blood flow rate was also found to be significant (P < 0.01). This study underscores the importance of the dialysis prescription parameters and vascular access site in influencing the dialysis dose in critically ill patients, and argues against the importance of patient-related characteristics such as disease severity.

APACHE↗

PubMed2004

Polymorphism of immunomodulatory cytokine genes: implications in acute renal failure.

Experimental studies have incriminated cytokines and other immunoregulatory molecules as important mediators of tissue injury in acute renal failure (ARF). The relative importance of genetic factors, e.g. polymorphisms involving cytokine genes, in influencing susceptibility to and severity of ARF is unknown. This review summarizes the existing experimental and clinical studies supporting the role of inflammation in ARF, and critically examines human studies that have examined polymorphism of two critical cytokine genes, tumor necrosis factor-alpha and interleukin-10, as potential determinants of susceptibility to and severity of acute infectious and inflammatory diseases. Conclusions are drawn on the application of genetic epidemiology to the field of ARF and the rationale for further research on the role of genetic markers in ARF.

Acute Kidney Injury↗

PubMed2004

Cytokine single nucleotide polymorphism. Role in acute renal failure.

Although the pathogenesis of ARF is heterogeneous and results from a combination of different environmental influences and host responses, there is overwhelming data to suggest a common pathway that involves pro- and anti-inflammatory molecules, which in turn, determines the extent of tissue injury. The number of recognized cytokine gene polymorphisms is growing daily. The development of cytokine gene mapping may help identify patients in whom an excessive systemic inflammatory response may follow a therapeutic intervention (e.g. CABG, contrast administration), and who may be at increased risk for developing acute organ dysfunction. Through these advances, tools may be developed to better understand, prevent and treat ARF. Genetic epidemiology studies may help characterize the importance of genetic markers in the development of ARF. This would require large prospective cohort studies aimed at examining associations between genetic markers, urinary (urine KIM-1 and NAG) and circulating (serum creatinine) markers of kidney injury. Once firmly established, the association of a particular genetic profile and outcome could be used to risk stratify patients for the development of ARF (fig. 4). Ultimately, cytokine-modulating therapies could be employed on the basis of genotypic risk stratification with the goal to prevent kidney injury or minimize its deleterious effects on patient outcome.

Acute Kidney Injury↗

PubMed2003

ARF after open-heart surgery: Influence of gender and race.

BACKGROUND: Both acute renal failure (ARF) and female sex are strongly associated with mortality after open-heart surgery. This study analyzes the effect of sex and race on the incidence of ARF after open-heart surgery and its influence on mortality. METHODS: A total of 24,660 patients underwent open-heart surgery at the Cleveland Clinic Foundation (Cleveland, OH) from 1993 to 2000. The primary outcome was ARF defined as ARF requiring dialysis, 50% or greater decline in glomerular filtration rate (GFR) not requiring dialysis, or 50% or greater decline in GFR relative to baseline or requirement of dialysis. The secondary outcome was all-cause hospital mortality. RESULTS: The overall frequency of ARF requiring dialysis after open-heart surgery was 1.82%. The frequency was greater in women (2.36%) than men (1.60%; P < 0.0001) and blacks (2.94%) than nonblacks (1.70%; P < 0.0001) by univariate analysis. By multivariate analysis, risk for ARF requiring dialysis in women was 1.61 (confidence interval [CI], 1.27 to 2.05; P < 0.0001), but race was not a risk factor. The overall postoperative mortality rate was 2.2%, and for patients with ARF requiring dialysis, it was 61.2% (women, 68.6% versus men, 56.5%; P = 0.01) with an odds ratio of 49.29, whereas in patients with ARF not requiring dialysis, it was 14.1% (women, 13.3% versus men 14.6%; P = 0.63) with an odds ratio of 7.18. CONCLUSION: Female sex is an independent risk factor for developing ARF after open-heart surgery. The influence of race on risk for ARF is less clear. Regardless of its definition, ARF is strikingly associated with a high risk for mortality.

Acute Kidney Injury↗

PubMed2003

Soluble Fas: a novel marker of inflammation in uremia.

BACKGROUND: Inflammation has been associated with atherosclerotic cardiovascular disease (CVD) and anemia in patients with end-stage renal disease (ESRD). Recent studies have shown that serum levels of soluble Fas (sFas), an antiapoptotic and proinflammatory molecule, are elevated in patients with cardiac disease and patients with ESRD. We therefore sought to investigate serum levels of sFas in uremic patients and its correlation with known markers of inflammation, anemia and CVD. METHODS: The study included 25 ESRD patients (14 on hemodialysis, 11 on CAPD), 27 patients with chronic kidney disease (CKD; creatinine clearance <50 ml/min/1.73 m2), and 14 normal control subjects. We measured serum levels of sFas, C-reactive protein (CRP), and albumin. We also investigated the association of serum sFas levels with the presence of CVD and with erythropoietin (EPO) dosage. RESULTS: Levels of sFas were elevated in CKD and ESRD patients compared to controls. sFas levels correlated negatively with creatinine clearance. In the dialysis patients, we observed that sFas levels were higher among those with CVD. Serum levels of sFas correlated with serum levels of CRP (r=0.31; P=0.03), serum levels of albumin (r=-0.35, P=0.02), and EPO dosage (r=0.51; P=0.009). CONCLUSION: These results suggest that sFas may be a marker of inflammation in CKD and ESRD patients.

Adult↗

PubMed2003

Anemia in acute renal failure: role for erythropoiesis-stimulating proteins?

The use of recombinant human erythropoietin (rHuEpo) has revolutionized anemia management of early and late stages of chronic kidney disease. Darbopoietin is also now available for the treatment of anemia of chronic kidney disease. In addition, rHuEpo has been used for the treatment of anemia observed in critical illness. Unfortunately, the existing clinical studies of anemia in critically ill patients do not distinguish between those with and without acute renal failure (ARF). This review summarizes the existing experimental and clinical studies supporting the use of rHuEpo in ARF due to ischemic/nephrotoxic injury and conclusions are drawn on the rationale for further research into the use of this drug in ARF.

Acute Kidney Injury↗

PubMed2002

Dialyzer fiber bundle volume and kinetics of solute removal in continuous venovenous hemodialysis.

The relationship between dialyzer fiber bundle volume (FBV), dialyzer life span, and small-solute clearance has yet to be clearly defined in continuous venovenous hemodialysis (CVVHD). This study sought to define this relationship using novel ultrasound dilution technology. We studied 55 sessions in 31 intensive care unit patients on CVVHD therapy. A session was defined as the life span of a single dialyzer. The following variables were assessed every 6 hours throughout each session, starting within 1 hour of initiation of that session: FBV, access recirculation, extracorporeal blood flow rate, effluent (EUN) to blood urea nitrogen (BUN) concentration ratio, effluent creatinine to blood creatinine concentration ratio, and urea nitrogen and creatinine clearances. Data were analyzed using random-effects linear models to estimate trends. Several dialysis-related and solute-removal parameters were analyzed for association with each other. Systemic or dialysis circuit heparin was administered in 28 of 55 sessions. One hundred seventy sets of FBV, 101 sets of urea clearance, and 102 sets of creatinine clearance measurements were performed. There was a declining trend for FBV (0.8 mL/h), heart rate (0.25 beats/min/h), and measured blood flow (0.33 mL/min/h; P < 0.05). Apart from dialysate inflow rate (P = 0.044), there was no significant correlation with EUN-BUN ratio. Session duration was associated with dialysis access site; the femoral access provided longer dialysis sessions than subclavian and internal jugular accesses (P = 0.029). We conclude that small-solute removal remains stable over the course of our CVVHD system life spans despite significant loss of hemodialyzer FBV.

Blood Urea Nitrogen↗

PubMedDate not supplied

Dialysis membrane and modality in acute renal failure: understanding discordant meta-analyses.

Meta-analyses of the published literature are increasingly being used, allowing similar clinical trials to be combined quantitatively, thereby increasing the precision of the estimation of treatment effect. Four meta-analyses were recently published comparing the impact of dialysis membranes or dialysis modality on clinical outcomes of patients with acute renal failure (ARF) requiring renal replacement therapy. Two studies compared dialysis membranes in intermittent hemodialysis (IHD) and two studies compared continuous renal replacement therapy (CRRT) to IHD. The findings between each pair of meta-analyses were discordant. This was due in part to the differences among meta-analyses in inclusion and exclusion criteria, the paucity of randomized controlled trials, variation in individual study quality, and heterogeneity in the study populations and settings. Understanding these issues is important to properly interpret results from these meta-analyses.

Acute Kidney Injury↗

PubMedDate not supplied

Model for gene-environment interaction: the case for dialysis.

Organ complications in end-stage renal disease (ESRD) such as cardiovascular disease, anemia, bone disease, malnutrition, inflammation, and infections occur in many organ systems and are caused by a multitude of underlying disease-, uremia-, and therapy-related factors, and with a wide range of manifestations and severity. Interindividual variability in the pathophysiologic response of the uremic host to environmental factors, including renal replacement therapy, may be governed to a significant degree by genetic susceptibility factors. Specific genes regulate the pathophysiologic responses of organ systems affected by ESRD and can serve as candidate genes for the host-environment interaction. This review summarizes emerging clinical and translational research work in the field of genetic polymorphism of candidate genes and their effects on the development of organ complications in ESRD. Methodologic limitations of the existing published data, the need for large prospective cohort studies, and potential future risks for the use of genomic information in resource allocation are also highlighted.

Cytokines↗

PubMedDate not supplied

Long-term management of the tunneled venous catheter.

Despite their propensity for significant complications, tunneled central venous catheters have become a common means of vascular access in the United States for patients requiring maintenance hemodialysis for end-stage renal disease (ESRD). Reasons for their use include advanced patient age, peripheral vascular disease (arterial and venous), late referral for creation of vascular access, and more importantly, the lack of an interdisciplinary service line on vascular access among vascular surgeons, radiologists, and nephrologists. This review article summarizes complications commonly encountered in dialysis patients who use tunneled central venous catheters for vascular access-mainly thrombosis, stenosis, and infection. Special attention is given to novel approaches for the prevention of catheter-associated infections. Effective prevention and timely treatment of common catheter-associated complications can reduce the substantial morbidity associated with the use of these devices. However, these measures should not detract from the goal of avoiding or limiting the long-term use of catheters, thereby optimizing vascular access management by ensuring the timely availability of functioning arteriovenous fistulas.

Bacteremia↗

PubMedDate not supplied

Update on dialytic management of acute renal failure.

The potential impact of renal replacement therapy on clinical outcomes in acute renal failure (ARF) remains a subject of ongoing investigation and controversy. This article reviews in depth the clinical trials to date that have examined the effect of dialysis-related variables on outcomes of patients with hospital-acquired ARF. In particular, the role of the dialysis modality, dialyzer characteristics, and dosing strategies are discussed. Clinical trials comparing intermittent hemodialysis (HD) to continuous renal replacement therapies (CRRT) have failed to demonstrate a survival difference when adjusting for disease severity. Similarly, studies evaluating dialyzer membrane biocompatibility and flux properties had no impact on survival. Efforts aimed at measuring dialysis adequacy in patients with ARF receiving HD using urea kinetic modeling are hindered by a lack of understanding of solute kinetics in this setting. However, dosing strategies during CRRT are promising. Finally, the application of cell therapy to the successful substitution of renal function shows promise for the future.

Acute Kidney Injury↗