Introduction

Acute kidney injury (AKI) diagnosis is based on an increase in plasma creatinine, which is a slowly changing surrogate of decreased glomerular filtration rate. We investigated whether serial creatinine clearance, a direct measure of the glomerular filtration rate, provided more timely and accurate information on renal function than serial plasma creatinine in critically ill patients.

Methods

Serial plasma creatinine and 4-hour creatinine clearance were measured 12-hourly for 24 hours and then daily in 484 patients. AKI was defined either as > 50% increase in plasma creatinine from baseline, or > 33.3% decrease in creatinine clearance. The diagnostic and predictive performance of the two AKI definitions were compared.

Results

Creatinine clearance decrease diagnosed AKI in 24% of those not diagnosed by plasma creatinine increase on entry. These patients entered the ICU sooner after insult than those diagnosed with AKI by plasma creatinine elevation (P = 0.0041). Mortality and dialysis requirement increased with the change in creatinine clearance-acute kidney injury severity class (P = 0.0021). Amongst patients with plasma creatinine < 1.24 mg/dl on entry, creatinine clearance improved the prediction of AKI considerably (Net Reclassification Improvement 83%, Integrated Discrimination Improvement 0.29). On-entry, creatinine clearance associated with AKI severity and duration (P < 0.0001) predicted dialysis need (area under the curve: 0.75) and death (0.61). A > 33.3% decrease in creatinine clearance over the first 12 hours was associated with a 2.0-fold increased relative risk of dialysis or death.

Conclusions

Repeated 4-hour creatinine clearance measurements in critically ill patients allow earlier detection of AKI, as well as progression and recovery compared to plasma creatinine.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN012606000032550.

Background

Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease.

Methods

The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic.

Principal findings

In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = −0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = −0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion.

Conclusions

Betaine excretion correlates with homocysteine in subjects with elevated blood lipids.

Personality traits are potential endophenotypes for genetic studies of psychiatric disorders. One personality theory which demonstrates strong heritability is Cloninger's psychobiological model measured using the temperament and character inventory (TCI). 277 individuals who completed the TCI questionnaire as part of the South Island Bipolar Study were also interviewed to assess for lifetime psychiatric diagnoses. Four groups were compared, bipolar disorder (BP), type 1 and 2, MDD (major depressive disorder), and nonaffected relatives of a proband with BP. With correction for mood state, total harm avoidance (HA) was higher than unaffected in both MDD and BP groups, but the mood disorder groups did not differ from each other. However, BP1 individuals had higher self-transcendence (ST) than those with MDD and unaffected relatives. HA may reflect a trait marker of mood disorders whereas high ST may be specific to BP. As ST is heritable, genes that affect ST may be of relevance for vulnerability to BP.

Monitoring of HF (heart failure) with intracardiac pressure, intrathoracic impedance and/or natriuretic peptide levels has been advocated. We aimed to investigate possible differences in the response patterns of each of these monitoring modalities during HF decompensation that may have an impact on the potential for early therapeutic intervention. Six sheep were implanted with a LAP (left atrial pressure) sensor and a CRT-D (cardiac resynchronization therapy defibrillator) capable of monitoring impedance along six lead configuration vectors. An estimate of ALAP (LAP from admittance) was determined by linear regression. HF was induced by rapid ventricular pacing at 180 and 220 bpm (beats/min) for a week each, followed by a third week with daily pacing suspensions for increasing durations (1–5 h). Incremental pacing induced progressively severe HF reflected in increases in LAP (5.9 ± 0.4 to 24.5 ± 1.6 mmHg) and plasma atrial (20 ± 3 to 197 ± 36 pmol/l) and B-type natriuretic peptide (3.7 ± 0.7 to 32.7 ± 5.4 pmol/l) (all P<0.001) levels. All impedance vectors decreased in proportion to HF severity (all P<0.001), with the LVring (left ventricular)-case vector correlating best with LAP (r2=0.63, P<0.001). Natriuretic peptides closely paralleled rapid acute changes in LAP during alterations in pacing (P<0.001), whereas impedance changes were delayed relative to LAP. ALAP exhibited good agreement with LAP. In summary, impedance measured with an LV lead correlates significantly with changes in LAP, but exhibits a delayed response to acute alterations. Natriuretic peptides respond rapidly to acute LAP changes. Direct LAP, impedance and natriuretic peptide measurements all show promise as early indicators of worsening HF. ALAP provides an estimate of LAP that may be clinically useful.

Introduction

To evaluate the utility of urinary cystatin C (uCysC) as a diagnostic marker of acute kidney injury (AKI) and sepsis, and predictor of mortality in critically ill patients.

Methods

This was a two-center, prospective AKI observational study and post hoc sepsis subgroup analysis of 444 general intensive care unit (ICU) patients. uCysC and plasma creatinine were measured at entry to the ICU. AKI was defined as a 50% or 0.3-mg/dL increase in plasma creatinine above baseline. Sepsis was defined clinically. Mortality data were collected up to 30 days. The diagnostic and predictive performances of uCysC were assessed from the area under the receiver operator characteristic curve (AUC) and the odds ratio (OR). Multivariate logistic regression was used to adjust for covariates.

Results

Eighty-one (18%) patients had sepsis, 198 (45%) had AKI, and 64 (14%) died within 30 days. AUCs for diagnosis by using uCysC were as follows: sepsis, 0.80, (95% confidence interval (CI), 0.74 to 0.87); AKI, 0.70 (CI, 0.64 to 0.75); and death within 30 days, 0.64 (CI, 0.56 to 0.72). After adjustment for covariates, uCysC remained independently associated with sepsis, AKI, and mortality with odds ratios (CI) of 3.43 (2.46 to 4.78), 1.49 (1.14 to 1.95), and 1.60 (1.16 to 2.21), respectively. Concentrations of uCysC were significantly higher in the presence of sepsis (P < 0.0001) or AKI (P < 0.0001). No interaction was found between sepsis and AKI on the uCysC concentrations (P = 0.53).

Conclusions

Urinary cystatin C was independently associated with AKI, sepsis, and death within 30 days.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN012606000032550.

Background

Vitamin D deficiency is associated with heightened risk of cardiovascular disease. Potential mechanisms include involvement of vitamin D in regulation of renin-angiotensin system and manufacture and secretion of cardiac natriuretic peptides. Our aim was to document relationships between 25 hydroxyvitamin [25(OH)D] and N-terminal pro B-type natriuretic peptide (NT-proBNP) and plasma renin activity (PRA) levels and to document the effect of vitamin D administration on NT-proBNP and PRA levels in vitamin D deficient subjects.

Methods

Serum 25(OH)D, parathyroid hormone (PTH), plasma or serum NT-proBNP and PRA levels were measured at baseline in nulliparous and lactating women and after 2 months of oral vitamin D2 (2,000 IU/day or 60,000 IU/month) supplementation to lactating women.

Results

Baseline levels of 25(OH)D were low (<50 nmol/L) in most women whereas PRA and NT-proBNP levels were within the normal range. There were no significant correlations between baseline 25(OH)D or PTH with NT-proBNP and PRA. Vitamin D administration over a 2-month period in lactating women was associated with a decline in NT-proBNP (by 9.1 ± 2.0 pmol/L; p < 0.001) and PRA (by 0.32 ± 0.17 nmol/L/hr; p = 0.064). However, there were no significant correlations between the changes from baseline in 25(OH)D and either NT-proBNP (r = -0.04, p = 0.8) or PRA (r = -0.04, p = 0.8).

Conclusion

We found no significant correlations between 25(OH)D or PTH with NT-proBNP and PRA in vitamin D deficient women. Further information is required to clarify the effects of vitamin D administration on cardiac structure and function.

Background

Adverse respiratory effects of particulate air pollution have been identified by epidemiological studies. We aimed to examine the health effects of ambient particulate air pollution from wood burning on school-age students in Christchurch, New Zealand, and to explore the utility of urine and exhaled breath condensate biomarkers of exposure in this population.

Methods

A panel study of 93 male students (26 with asthma) living in the boarding house of a metropolitan school was undertaken in the winter of 2004. Indoor and outdoor pollution data was continuously monitored. Longitudinal assessment of lung function (FEV1 and peak flow) and symptoms were undertaken, with event studies of high pollution on biomarkers of exposure (urinary 1-hydroxypyrene) and effect (exhaled breath condensate (EBC) pH and hydrogen peroxide concentration).

Results

Peak levels of air pollution were associated with small but statistically significant effects on lung function in the asthmatic students, but not healthy students. No significant effect of pollution could be seen either on airway inflammation and oxidative stress either in healthy students or students with asthma. Minor increases in respiratory symptoms were associated with high pollution exposure. Urinary 1-hydroxypyrene levels were raised in association with pollution events by comparison with low pollution control days.

Conclusion

There is no significant effect of ambient wood-smoke particulate air pollution on lung function of healthy school-aged students, but a small effect on respiratory symptoms. Asthmatic students show small effects of peak pollution levels on lung function. Urinary 1-hydroxypyrene shows potential as a biomarker of exposure to wood smoke in this population; however measurement of EBC pH and hydrogen peroxide appears not to be useful for assessment of population health effects of air pollution.

Some of the data presented in this paper has previously been published in Kingham and co-workers Atmospheric Environment, 2006 Jan; 40: 338–347 (details of pollution exposure), and Cavanagh and co-workers Sci Total Environ. 2007 Mar 1;374(1):51-9 (urine hydroxypyrene data).

Background

Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients.

Methods

Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days.

Principal Findings

The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002).

Conclusions

Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk.