Madhumati Rao

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.

Physicochemical properties of ferumoxytol, a new intravenous iron preparation

Background  Intravenous iron is a critical component of anaemia management. However, currently available preparations have been associated with the release of free iron, a promoter of bacterial growth and oxidative stress.

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.

Genetics and reverse epidemiology among patients on chronic hemodialysis.

A reversal in the association between traditional and nontraditional risk factors and clinical outcomes is often encountered in patients with chronic illness, including among those with advanced chronic kidney disease (CKD) on maintenance hemodialysis (MHD). The effects of the malnutrition–inflammation complex syndrome (MICS) may play a significant role in the reversal of this risk factor‐outcomes association. the MICS, this syndrome complex is not universal in its prevalence among MHD patients. The significant inter‐ and intra‐individual differences in the prevalence of inflammation, oxidative stress, and malnutrition, indicates the influence of genetic factors in this variability. In recent years, enormous advancement in the field of molecular genetics, genomics and bioinformatics, have revolutionized studies of the genetic epidemiology of several diseases. However, genetic association studies are at a preliminary stage in the population with advanced CKD ( Table 1 ). Preliminary studies of the impact of polyphisms in inflammation and oxidative stress‐related genes and genes affecting body composition and metabolism suggest that genetic variation may indeed affect the phenotype of the MHD population. Further, some of these gene polymorphisms may also contribute to a reversal of the association between traditional risk factors, such as BMI, blood pressure, and cholesterol and clinical outcomes in this vulnerable patient population. Genetic studies in patients with advanced CKD pose enormous challenges, including recruitment of sufficient numbers of patients to achieve adequate statistical power, resolution of immense genotypic and phenotypic heterogeneity, and gene–environment and gene–gene interactions. However, well‐designed adequately powered studies with carefully defined phenotypes may potentially allow definition of risk profiles characterized by combinations of relevant Single nucleotide polymorphisms in the setting of given environmental factors. Accurate risk stratification that takes into account genetic information would allow more informed targeting of pharmacologic intervention and better refined clinical trial methodologies.

CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Genetics and Reverse Epidemiology Among Patients on Chronic Hemodialysis

A reversal in the association between traditional and nontraditional risk factors and clinical outcomes is often encountered in patients with chronic illness, including among those with advanced chronic kidney disease (CKD) on maintenance hemodialysis (MHD). The effects of the malnutrition–inflammation complex syndrome (MICS) may play a significant role in the reversal of this risk factor‐outcomes association. the MICS, this syndrome complex is not universal in its prevalence among MHD patients. The significant inter‐ and intra‐individual differences in the prevalence of inflammation, oxidative stress, and malnutrition, indicates the influence of genetic factors in this variability. In recent years, enormous advancement in the field of molecular genetics, genomics and bioinformatics, have revolutionized studies of the genetic epidemiology of several diseases. However, genetic association studies are at a preliminary stage in the population with advanced CKD ( Table 1 ). Preliminary studies of the impact of polyphisms in inflammation and oxidative stress‐related genes and genes affecting body composition and metabolism suggest that genetic variation may indeed affect the phenotype of the MHD population. Further, some of these gene polymorphisms may also contribute to a reversal of the association between traditional risk factors, such as BMI, blood pressure, and cholesterol and clinical outcomes in this vulnerable patient population. Genetic studies in patients with advanced CKD pose enormous challenges, including recruitment of sufficient numbers of patients to achieve adequate statistical power, resolution of immense genotypic and phenotypic heterogeneity, and gene–environment and gene–gene interactions. However, well‐designed adequately powered studies with carefully defined phenotypes may potentially allow definition of risk profiles characterized by combinations of relevant Single nucleotide polymorphisms in the setting of given environmental factors. Accurate risk stratification that takes into account genetic information would allow more informed targeting of pharmacologic intervention and better refined clinical trial methodologies.

CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Genetics and Reverse Epidemiology Among Patients on Chronic Hemodialysis: REVERSE EPIDEMIOLOGY AMONG PATIENTS ON CHRONIC HEMODIALYSIS

A reversal in the association between traditional and nontraditional risk factors and clinical outcomes is often encountered in patients with chronic illness, including among those with advanced chronic kidney disease (CKD) on maintenance hemodialysis (MHD). The effects of the malnutrition–inflammation complex syndrome (MICS) may play a significant role in the reversal of this risk factor‐outcomes association. the MICS, this syndrome complex is not universal in its prevalence among MHD patients. The significant inter‐ and intra‐individual differences in the prevalence of inflammation, oxidative stress, and malnutrition, indicates the influence of genetic factors in this variability. In recent years, enormous advancement in the field of molecular genetics, genomics and bioinformatics, have revolutionized studies of the genetic epidemiology of several diseases. However, genetic association studies are at a preliminary stage in the population with advanced CKD ( Table 1 ). Preliminary studies of the impact of polyphisms in inflammation and oxidative stress‐related genes and genes affecting body composition and metabolism suggest that genetic variation may indeed affect the phenotype of the MHD population. Further, some of these gene polymorphisms may also contribute to a reversal of the association between traditional risk factors, such as BMI, blood pressure, and cholesterol and clinical outcomes in this vulnerable patient population. Genetic studies in patients with advanced CKD pose enormous challenges, including recruitment of sufficient numbers of patients to achieve adequate statistical power, resolution of immense genotypic and phenotypic heterogeneity, and gene–environment and gene–gene interactions. However, well‐designed adequately powered studies with carefully defined phenotypes may potentially allow definition of risk profiles characterized by combinations of relevant Single nucleotide polymorphisms in the setting of given environmental factors. Accurate risk stratification that takes into account genetic information would allow more informed targeting of pharmacologic intervention and better refined clinical trial methodologies.