PubMed Health⌕ Search

Biomedical subjects

Bertrand L Jaber

Publications and source records attributed to Bertrand L Jaber.

At least 19 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

Incidence and prevalence of hyponatremia.

Hyponatremia is the most common electrolyte abnormality encountered in clinical practice. The reported frequency of the disorder is determined by a number of factors, including the definition of hyponatremia, the frequency of testing, the healthcare setting, and the patient population. This review focuses on the incidence and prevalence of hyponatremia. In acute hospital care, particular attention is given to admission versus hospital-acquired hyponatremia. Although less well studied, the epidemiology of hyponatremia in the ambulatory-based setting and the geriatric/nursing home population is also summarized. Finally, the frequency of hyponatremia occurring in special clinical conditions--including congestive heart failure, cirrhosis, pneumonia, and acquired immunodeficiency syndrome--as well as in marathon runners will be reviewed. Substantial additional work is still required to determine the true occurrence of hyponatremia in the various clinical settings. Beyond the phenomenologic value, advances in the epidemiology of hyponatremia should also provide insights in the prognostic implications as well as the preventive and management strategies of the disorder in various clinical settings.

Acquired Immunodeficiency Syndrome↗
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↗
PubMed2005

Progression of chronic kidney disease: can it be prevented or arrested?

Chronic kidney disease constitutes a highly prevalent health problem worldwide. Left untreated, it progresses inexorably to greater levels of severity at variable rates. The morbid impact of chronic kidney disease is heightened by its role as risk factor for cardiovascular disease. In the past two decades, considerable gains have been realized in retarding progression of chronic kidney disease by emphasizing blood pressure control and blockade of the renin-angiotensin system. Notwithstanding, the therapeutic goal of preventing or arresting chronic kidney disease progression remains unfulfilled. Currently attainable rates of decrease in glomerular filtration rate remain at 2 to 8 mL/min/y depending on the underlying disease. It is now believed that to achieve optimal therapeutic targets (proteinuria of <500 mg/day and decrease in glomerular filtration rate of 1 mL/min/y, the average age-related decline) we must introduce novel strategies and a multifaceted approach to treatment that interrupts multiple mechanisms of progression. To this end, and wherever relevant, new approaches to cause-specific treatment must be applied, such as targeted immunosuppression, intensive glycemic control, gene therapy, and enzyme replacement therapy. Furthermore, in all chronic kidney disease, we must interfere more effectively with the multitude of common mechanisms of progression. Established or putative, such approaches include aggressive blood pressure control; advanced renin-angiotensin system blockade; cytokine modulation and antifibrotic therapy; aldosterone blockade; endothelin blockade, nitric oxide modulation and vasopeptidase inhibition; antioxidant therapy; statin therapy; glycosaminoglycan therapy; anemia therapy; dietary restrictions; lifestyle changes; and pharmacogenomic profiling. Such a concerted, multifaceted approach to management might indeed prevent or arrest progression of chronic kidney disease, or even achieve regression of chronic kidney disease.

Anemia↗
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↗
PubMed2005

Polymorphism of host response genes: implications in the pathogenesis and treatment of acute renal failure.

Acute inflammatory disorders are the result of an interaction between genetic and environmental factors, and are often characterized by an imbalance between pro- and anti-inflammatory host immune responses. Over the past decade, polymorphisms of host response genes have been explored as genetic risk and prognostic markers in the course and severity of acute inflammatory disorders. Increasing evidence supports an important role for inflammatory mechanisms in the pathogenesis of acute renal failure (ARF) following both ischemic and nephrotoxic injury. The use of genetic epidemiology may become a useful tool to identify patients with an altered susceptibility to developing hospital-acquired ARF, and stratify those who may benefit from preventive therapies that modulate host immune responses in a favorable way. This review summarizes the existing experimental and clinical studies supporting the role of inflammation in ARF and critically appraises studies that have examined polymorphism of immune response genes as potential determinants of susceptibility to and severity of acute inflammatory disorders. 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↗
PubMed2005

Immune-modulating effects of melatonin, N-acetylserotonin, and N-acetyldopamine.

Melatonin and N-acetylserotonin (NAS) have antioxidant properties. In the present study, we examined whether melatonin, NAS, and N-acetyldopamine (NAD) have a modulatory effect on tumor necrosis factor-alpha (TNF-alpha) synthesis and superoxide production. Differentiated THP-1-derived human monocytes were coincubated with Escherichia coli lipopolysaccharide (LPS) and rising concentrations of melatonin, NAS, or NAD. After 24 h, TNF-alpha was measured in cell supernatants. In addition, the production of superoxide by HL-60-derived human neutrophils upon stimulation with 4-beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) or N-formyl methionyl-leucyl-phenylalanine (fMLP) and increasing concentrations of melatonin, NAS, or NAD was determined. Incubation of THP-1-derived monocytes with increasing concentrations of melatonin, NAS, or NAD resulted in a marked decrease in LPS-stimulated TNF-alpha production, which was dose-dependent and on the order of 96-98%. Incubation of HL-60-derived neutrophils with increasing concentrations of melatonin, NAS, or NAD resulted in a modest decrease in PMA-stimulated superoxide production, which was dose-dependent. At the 100 microM dose, melatonin, NAS, or NAD resulted in a 14 +/- 4%, 30 +/- 1%, and 29 +/- 1% decrease in PMA-stimulated superoxide production, respectively. Coincubation of HL-60 cells with melatonin, NAS, or NAD also resulted in a modest dose-dependent decrease in fMLP-stimulated superoxide production. At the 100 microM dose, melatonin, NAS, or NAD resulted in a 13 +/- 1%, 14 +/- 1%, and 14 +/- 1% decrease in superoxide production, respectively. Our results indicate that the inhibitory effect of melatonin, NAS, or NAD on LPS-induced TNF-alpha production is robust and dose-dependent. These compounds are equally effective in attenuating the generation of oxidant radicals, although to a lesser degree.

Antioxidants↗
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

Daily hemofiltration for end-stage renal disease: a feasibility and efficacy trial.

BACKGROUND: Although conventional hemodialysis (CHD) is currently provided primarily on an intermittent basis for patients with end-stage renal diseases (ESRD), the value of daily dialysis is well documented. Daily hemofiltration (DHF) is a convective therapy that has received little attention as an alternative to CHD. The aim of this feasibility study was to validate and assess the efficacy of DHF (6 times/week) as an alternative to CHD (3 times/week) in patients with ESRD. METHODS: In this prospective single-arm open-labeled study, DHF was administered over 4 weeks after a 1-week run-in phase period of CHD. Blood samples were drawn at baseline and on a weekly basis during the trial, and ultrafiltrate samples were collected weekly during the DHF period. The primary endpoint was to achieve a daily spKt/V of 0.40 (equivalent to a weekly stdKt/V of approximately 2.0). To achieve this goal, the DHF prescription consisted of an exchange volume of 40% of total body water. Secondary endpoints were the evaluation of blood pressure and anemia parameters, nutritional and mineral metabolism markers and health-related quality of life measures. RESULTS: Twelve patients completed the study. Mean age was 54 years, two-thirds were men, and 83% had arteriovenous fistulae. DHF delivered a mean (+/-SD) spKt/V of 0.44 +/- 0.06. This goal was reached by delivering an exchange volume of 13-14 liters, consisting of a replacement fluid volume of 11.7 +/- 1.9 l/session and net fluid loss of 1.4 +/- 0.1 l/session. Conversion from CHD to DHF resulted in marked reduction in treatment time (3.8 vs. 2 h/session, p < 0.001) and net fluid loss (2.6 vs. 1.4 l/session, p < 0.001). Calculated weekly standard Kt/V during the last week of DHF was 1.9 +/- 0.2. DHF achieved a median beta2-microglobulin (beta2-M) removal of 170 mg/session, resulting in a decrease of mid-week pre-therapy beta2-M levels (48 +/- 34 vs. 36 +/- 25 mg/l, p = 0.07). Compared with CHD, DHF resulted in lower systolic (143 +/- 19 vs. 133 +/- 16 mm Hg, p = 0.002) and diastolic (79 +/- 11 vs. 72 +/- 12 mm Hg, p = 0.002) blood pressure, reduction in antihypertensive medications (2.1 +/- 0.7 vs. 1.1 +/- 0.8, p = 0.002), higher caloric intake (1,778 +/- 441 vs. 2,044 +/- 564 kcal/day, p = 0.01), higher normalized protein catabolic rate (0.88 +/- 0.17 vs. 1.00 +/- 0.35 g/kg/day, p = 0.05), higher pre-albumin levels (330 +/- 50 vs. 378 +/- 84 g/dl, p = 0.06), higher vitality (p = 0.02), improved cognitive function (p = 0.04) and less symptoms/problems (p = 0.03). Serum albumin and potassium levels remained unchanged but the serum bicarbonate level dropped during the 1-month period of DHF. CONCLUSIONS: DHF (6 times/week) over a 1-month period achieved a weekly stdKt/V of approximately 2.0, which is similar to that recommended for 3 times weekly CHD, reduced beta2-M levels, lowered blood pressure, and had some beneficial effect on nutritional parameters, and health-related quality of life measures.

Adolescent↗
PubMed2004

Iron storage indices: novel predictors of bacteremia in hemodialysis patients initiating intravenous iron therapy.

Bacterial sepsis is the second leading cause of death among hemodialysis (HD) patients. Iron overload and intravenous iron therapy are linked to bacterial infection. This study examined iron stores, intravenous iron dosing, and bacteremic risk in HD patients. Retrospectively, 132 HD patients receiving their first course of intravenous iron were studied. Baseline laboratory values, including transferrin saturation (TSAT) value and ferritin level, were measured before initiating intravenous iron therapy. Patients were followed for up to 1 year after the initiation of iron therapy for the outcome of bacteremia by Cox proportional hazards regression analysis. Iron-replete patients (those with a TSAT value > or =20% and a ferritin level > or =100 ng/mL) had a significantly higher risk of bacteremia (hazard ratio [HR], 2.5). Venous catheter users (HR, 4.9) and those with diabetes mellitus (HR, 2.2) were also at increased risk. Modest iron storage levels may increase the risk of bacteremia among HD patients initiating intravenous iron therapy. Additional studies are needed to confirm these relationships.

Bacteremia↗
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↗