Effects of Ionic Strength, Salt, and pH on Aggregation of Boehmite Nanocrystals: Tumbler Small-Angle Neutron and X-ray Scattering and Imaging Analysis.

The US government currently spends significant resources managing the legacies of the Cold War, including 300 million liters of highly radioactive wastes stored in hundreds of tanks at the Hanford (WA) and Savannah River (SC) sites. The materials in these tanks consist of highly radioactive slurries and sludges at very high pH and salt concentrations. The solid particles primarily consist of aluminum hydroxides and oxyhydroxides (gibbsite and boehmite), although many other materials are present. These form complex aggregates that dramatically affect the rheology of the solutions and, therefore, efforts to recover and treat these wastes. In this paper, we have used a combination of transmission and cryo-transmission electron microscopy, dynamic light scattering, and X-ray and neutron small and ultrasmall-angle scattering to study the aggregation of synthetic nanoboehmite particles at pH 9 (approximately the point of zero charge) and 12, and sodium nitrate and calcium nitrate concentrations up to 1 m. Although the initial particles form individual rhombohedral platelets, once placed in solution they quickly form well-bonded stacks, primary aggregates, up to ∼1500 Å long. These are more prevalent at pH = 12. Addition of calcium nitrate or sodium nitrate has a similar effect as lowering pH, but approximately 100 times less calcium than sodium is needed to observe this effect. These aggregates have fractal dimension between 2.5 and 2.6 that are relatively unaffected by salt concentration for calcium nitrate at high pH. Larger aggregates (>∼4000 Å) are also formed, but their size distributions are discrete rather than continuous. The fractal dimensions of these aggregates are strongly pH-dependent, but only become dependent on solute at high concentrations.

Transferrin Saturation: A Body Iron Biomarker.

Iron is an essential element for several metabolic pathways and physiological processes. The maintenance of iron homeostasis within the human body requires a dynamic and highly sophisticated interplay of several proteins, as states of iron deficiency or excess are both potentially deleterious to health. Among these is plasma transferrin, which is central to iron metabolism not only through iron transport between body tissues in a soluble nontoxic form but also through its protective scavenger role in sequestering free toxic iron. The transferrin saturation (TSAT), an index that takes into account both plasma iron and its main transport protein, is considered an important biochemical marker of body iron status. Its increasing use in many health systems is due to the increased availability of measurement methods, such as calorimetry, turbidimetry, nephelometry, and immunochemistry to estimate its value. However, despite its frequent use in clinical practice to detect states of iron deficiency or iron overload, careful attention should be paid to the inherent limitations of the test especially in certain settings such as inflammation in order to avoid misinterpretation and erroneous conclusions. Beyond its usual clinical use, an emerging body of evidence has linked TSAT levels to major clinical outcomes such as cardiovascular mortality. This has the potential to extend the utility of TSAT index to risk stratification and prognostication. However, most of the current evidence is mainly driven by observational studies where the risk of residual confounding cannot be fully eliminated. Indeed, future efforts are required to fully explore this capability in well-designed clinical trials or prospective large-scale cohorts.

Transferrin saturation ratio and risk of total and cardiovascular mortality in the general population.

BACKGROUND: The transferrin saturation (TSAT) ratio is a commonly used indicator of iron deficiency and iron overload in clinical practice but precise relationships with total and cardiovascular mortality are unclear. PURPOSE: To better understand this relationship, we explored the association of TSAT ratio (serum iron/total iron binding capacity) with mortality in the general population. METHODS: The relationships of TSAT ratio with total and cardiovascular mortality were explored in 15 823 subjects age 20 and older from the Third National Health and Nutrition Examination Survey (1988-94). All subjects had vital status assessed through to 2006. RESULTS: During follow-up, 9.7% died of which 4.4% were from cardiovascular disease. In unadjusted analysis, increasing TSAT ratio was inversely associated with mortality. With adjustment for baseline demographic and clinical characteristics, the TSAT-mortality relationship followed a j-shaped pattern. Compared with the referent group [ratio 23.7-31.3%: hazard ratio (HR) =1.00], subjects in the lowest two quartiles, <17.5 % and 17.5-23.7 %, experienced significantly higher mortality risks of 1.45 (1.19-1.77) and 1.27 (1.06-1.53), respectively, whereas subjects in the highest quartile, >31.3 %, experienced significantly higher mortality risks of 1.23 (1.01-1.49). The pattern of association was more pronounced for cardiovascular mortality with significantly higher mortality risks for the lowest two quartiles [HR = 2.09 (1.43-3.05) and 1.90 (1.33-2.72), respectively] and highest quartile HR = 1.59 (1.05-2.40). CONCLUSIONS: Both low and high TSAT ratios are significantly and independently associated with increased total and cardiovascular mortality. The optimal TSAT ratio associated with the greatest survival is between 24% and 40%.

Plasma fibrinogen associates independently with total and cardiovascular mortality among subjects with normal and reduced kidney function in the general population.

BACKGROUND: The contribution of novel risk factors to mortality in chronic kidney disease remains controversial. AIM: To explore the association of plasma fibrinogen with mortality among individuals with normal and reduced kidney function. METHODS: We identified 9184 subjects, age 40 and over from the Third National Health and Nutrition Examination Survey (1988-94) with vital status assessed through 2006. Plasma fibrinogen was modeled as continuous variable and in quartile groups (0 to <7.7, 7.7 to <9.0, 9.0 to <10.5 and ≥ 10.5 µmol/l) with total and cardiovascular mortality across categories of glomerular filtration rate (eGFR); <60, 60-90, >90 ml/min/1.73 m(2) using Cox regression. RESULTS: In multivariate analysis, the adjusted hazard ratio (HR) per 1 µmol/l (34 mg/dl) increase in fibrinogen was 1.07 [95% confidence interval (CI) 1.04-1.09] for total mortality and 1.06 (95% CI 1.03-1.09) for cardiovascular mortality. The adjusted HR for total mortality was 1.05 (1.01-1.09) for subjects with eGFR 60-90 ml/min/1.73 m(2) and 1.06 (1.02-1.10) for subjects with eGFR <60 ml/min/1.73 m(2). Subjects in the highest quartiles within each eGFR category; >90, 60-90 and <60 ml/min/1.73 m(2) experienced HRs of 1.45 (95% CI 1.03-2.03), 1.35 (95% CI 1.00-1.83) and 1.72 (95% CI 1.14-2.58), respectively, compared with subjects in the lowest quartile group. The patterns were similar for cardiovascular mortality. CONCLUSIONS: Plasma fibrinogen associates with mortality among subjects with mild to moderate kidney impairment as it does in subjects with normal kidney function and should be considered a therapeutic target for cardiovascular risk reduction.

Independent and conjoint associations of gout and hyperuricaemia with total and cardiovascular mortality.

BACKGROUND: Gout and serum uric acid are associated with mortality but their simultaneous contributions have not been fully evaluated in the general population. PURPOSE: To explore the independent and conjoint relationships of gout and uric acid with mortality in the US population. METHODS: Mortality risks of gout and serum uric acid were determined for 15 773 participants, aged 20 years or older, in the Third National Health and Nutrition Examination Survey by linking baseline information collected during 1988-1994 with mortality data up to 2006. Multivariable Cox proportional hazards regression determined adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each exposure and all analyses were conducted in 2011 and 2012. RESULTS: Compared with subjects without a history of gout, the multivariable HR for subjects with gout were 1.42 (CI 1.12-1.82) for total and 1.58 (CI 1.13-2.19) for cardiovascular mortality. Adjusted HRs per 59.5 µmol/l (1 mg/dl) increase in uric acid were 1.16 (CI 1.10-1.22) for total and cardiovascular mortality and this pattern was consistent across disease categories. In the conjoint analysis, the adjusted HRs for mortality in the highest two uric acid quartiles were 1.64 (CI 1.08-2.51) and 1.77 (CI 1.23-2.55), respectively, for subjects with gout, and were 1.09 (CI 0.87-1.37) and 1.37 (CI (1.11-1.70), respectively, for subjects without gout, compared with those without gout in the lowest quartile. A similar pattern emerged for cardiovascular mortality. CONCLUSION: Gout and serum uric acid independently associate with total and cardiovascular mortality. These risks increase with rising uric acid concentrations.

A cross-sectional study of the prevalence and clinical correlates of congestive heart failure among incident US dialysis patients.

Epidemiological characteristics of congestive heart failure (CHF) have not been well studied in patients with end-stage renal disease (ESRD). We evaluated the prevalence and clinical correlates of CHF using data from Wave 2 of the US Renal Data System Dialysis Morbidity and Mortality Study, a national random sample of incident hemodialysis and peritoneal dialysis patients in 1996 and 1997 (n = 4,024). CHF was recorded as present in 36% of patients. In multivariate analysis, age, female sex, hypertension, diabetes, measures of atherosclerosis, and structural cardiac abnormalities were significantly associated with the presence of CHF. Elevated serum phosphate level >/= 6.8 mg/dL (versus <6.8 mg/dL) and serum calcium level >/= 8.0 mg/dL (versus <8.0 mg/dL) were associated with significantly more CHF (odds ratios, 1.34 and 1.41, respectively), as were low serum albumin (odds ratio, 1.35 per 1-g/dL lower) and low serum cholesterol levels (odds ratio, 1.03 per 20-mg/dL lower). Of elements of pre-ESRD care, frequent visits to a nephrologist (odds ratio, 0.80) or dietitian (odds ratio, 0.84) were associated with significantly lower odds of CHF at the start of ESRD compared with less frequent visits. This national study shows the association of several measures of atherosclerosis and cardiac abnormalities with the presence of CHF at the start of dialysis therapy. It identifies serum albumin as a strong disease correlate and suggests that elevated serum calcium and phosphate levels may be potential risk factors for CHF. This study also suggests that frequent specialist care during this critical period may impact favorably on the prevalence of CHF at the start of ESRD. Future longitudinal studies are required to evaluate the impact of pre-ESRD care on cardiovascular and other clinical outcomes.

Renal replacement therapy in the elderly: medical, ethical, and psychosocial considerations.

As patients over the age of 65 become the fastest growing segment of our treated end-stage renal disease (ESRD) population, nephrologists and allied healthcare workers who care for these patients must become well versed in the many issues specific to this group. Elderly patients contribute the greatest fraction to the incidence and prevalence of the United States ESRD population. Their life expectancy is greatly reduced compared with age-matched counterparts from the general population. Cardiac disease is the leading cause of death. Although renal transplantation remains the most successful form of renal replacement therapy, only a small fraction of elderly ESRD patients are transplanted. The renal research community has made great strides in improving patient outcomes on dialysis over the last decade in many areas; however, little attention has been focused on the elderly ESRD patient. The substantial mortality and comorbidity experienced by this population makes their management an ongoing challenge. Many unresolved issues remain for elderly ESRD patients in the timing of dialysis initiation, choice of dialytic therapy, use of renal transplantation, and management of cardiovascular disease. It is anticipated that future research in these areas will identify optimal treatment strategies for elderly ESRD patients starting on dialysis and improve patient outcomes.