Ammonia clearance with haemofiltration in adults with liver disease.

BACKGROUND & AIMS: Ammonia is recognized as a toxin central to complications of liver failure. Hyperammonaemia has important clinical consequences, but optimal means to reduce circulating levels are uncertain. In patients with liver disease, continuous renal replacement therapy (CRRT) with haemofiltration (HF) is often required to treat concurrent kidney injury, but its effects upon ammonia levels are poorly characterized. To evaluate the effect of HF at different treatment intensities on ammonia clearance (AC) and arterial ammonia concentration. METHODS: Prospective study of adult patients with liver failure and arterial ammonia >100 µmol/L requiring CRRT using veno-venous HF. Arterial ammonia concentration and AC measured at 1 and 24 h after initiation of low (35 ml/kg/h) or high (90 ml/kg/h) filtration volume. RESULTS: Twenty-four patients (10 acute liver failure, 10 chronic liver disease and 4 following liver resection) were studied. Clearance of urea and ammonia solutes correlated closely (r = 0.819, P = 0.007). Ammonia clearance correlated closely with ultrafiltration rate (r = 0.86, P < 0.001). At 1 h, AC was 39 (34-54) ml/min (low volume) vs 85 (62-105) ml/min (high volume) CRRT, (P < 0.001) and at 24 h 44 (34-63) vs 105 (82-109) ml/min, (P = 0.01). Overall, a 22% reduction in median arterial ammonia concentration was observed over 24 h of HF from 156 (137-176) to 122 (85-133) µmol/L, (P ≤ 0.0001). CONCLUSION: Clinically significant ammonia clearance can be achieved in adult patients with hyperammonaemia utilizing continuous VVHF. Ammonia clearance is closely correlated with ultrafiltration rate. HF was associated with a fall in arterial ammonia concentration.

Intra-individual variability of serum hepcidin-25 in haemodialysis patients using mass spectrometry and ELISA.

BACKGROUND: Measurement of serum hepcidin levels may provide a useful alternative to the current methods of determining iron status in chronic haemodialysis (HD) patients. However, the biological variability of this pivotal regulator of iron homeostasis is unclear, and the impact of inflammation, dialysis clearance and iron therapy on hepcidin variability has not been established. METHODS: Two independent studies in chronic HD patients were conducted; serum hepcidin levels were measured at the start of dialysis sessions in 20 UK patients and in 43 Dutch patients by mass spectrometry (MS). Samples from UK patients were also analysed by a competitive enzyme-linked immunosorbent assay (cELISA). Coefficient of variance (CV(1)) was calculated and potential factors affecting CV(1) were also examined. RESULTS: The median CV(1) (inter-quartile range) was 23% (17-28) for the UK MS, 26% (17-48) for the Dutch MS and 23% (17-39) for the UK cELISA. The CV(1) was similar in those patients receiving and those not receiving regular intravenous iron. The CV(1) was not associated with the degree of inflammation. Hepcidin levels were higher following an inter-dialytic period of 3 versus 2 days (P = 0.02). CONCLUSIONS: These findings suggest considerable variability of serum hepcidin levels in HD patients. Inflammation and the use of iron did not impact on the degree of variability, and hepcidin levels were higher after an inter-dialytic period of 3 versus 2 days. These findings need to be taken into account in future studies assessing the utility of serum hepcidin as a guide to the use of iron or erythropoiesis-stimulating agents therapy.

Serum hemojuvelin and hepcidin levels in chronic kidney disease.

BACKGROUND: Hemojuvelin (HJV) has recently emerged as one of a number of significant regulators of iron homeostasis and hepcidin expression. Recently, an immunoassay has been developed to measure circulating levels of soluble HJV (sHJV). The aim of this study was to measure serum hepcidin and sHJV levels in a chronic kidney disease (CKD) population. METHODS: A total of 93 patients participated in the study (31 hemodialysis, 31 non-dialysis, 31 transplant recipients), and were matched for age and gender. Serum samples were taken for measurement of hepcidin-25 and sHJV, along with standard hematological, biochemical and inflammatory markers, and univariate/multivariate analyses were performed. RESULTS: Serum sHJV levels were markedly elevated in the hemodialysis patients (2,619 ± 1,445 ng/ml) compared to the CKD (590 ± 344 ng/ml) and transplant recipients (870 ± 638 ng/ml) (p < 0.001), normal range 370-890 ng/ml. There was a strong correlation between serum ferritin and sHJV, which remained after adjustment for potential confounders (beta 0.92, p < 0.001). In the univariate analysis, sHJV levels correlated with serum hepcidin but this was not evident in the multivariate analysis. No associations were seen between sHJV and markers of inflammation or eGFR. CONCLUSIONS: sHJV is elevated in hemodialysis patients compared to non-dialysis CKD patients. There was no association between sHJV and eGFR (in the non-dialysis groups), suggesting that factors other than decreased renal clearance are responsible for the high sHJV levels. The strong association between sHJV and ferritin suggests an interdependent relationship, although further studies are required to elucidate the possible mechanism(s) for this.

Remote intermittent ischemia before coronary artery bypass graft surgery: a strategy to reduce injury and inflammation?

Perioperative myocardial ischemia contributes to postoperative morbidity and mortality. Remote intermittent ischemia (RI) has been shown to benefit patients undergoing coronary artery bypass graft (CABG) surgery by decreasing postoperative cardiac troponin levels. In addition, there is evidence that volatile anesthetics may provide myocardial protection. In this prospective randomized controlled trial we tested the hypothesis that RI is cardioprotective under a strict anesthetic regime with volatile anesthesia until cardiopulmonary bypass (CPB). We also assessed whether RI modulates postoperative cytokine and growth factor concentrations. Fifty-four patients referred for elective CABG surgery without concomitant valve or aortic surgery were randomized to three 5-min cycles of left upper limb ischemia by cuff inflation (RI) or placebo without cuff inflation (Plac). All patients received the volatile anesthetic isoflurane (1.15-1.5 vol%) before CPB and the intravenous anesthetic propofol (3-4 mg/kg/h) thereafter until the end of surgery. Cardiac arrest during CPB was induced by intermittent cross-clamp fibrillation, or by blood cardioplegia. We excluded patients older than 85 years, with unstable angina, significant renal disease, and those taking sulfonylureas. Troponin I (cTnI) was measured preoperatively and after 6, 12, 24 and 48 h. In addition, brain natriuretic peptide (BNP), creatine kinase (CKMB) and a panel of cytokines and growth factors were analyzed perioperatively. Although cTnI, BNP and CKMB all increased post-CABG, there were no significant differences between RI and Plac groups; area under the curve for cTnI 189.4 (183.6) ng/mL/48 h and 183.0 (155.2) ng/mL/48 h mean (SD), p = 0.90, respectively, despite a tendency to a shorter (p < 0.07) cross-clamp time in the treatment group. Similarly, there were no differences between groups in the central venous concentrations of numerous cytokines and growth factors. In patients undergoing CABG surgery RI does not provide myocardial protection under a strict anesthetic regime with volatile anesthesia until CPB, and RI was not associated with changes in cytokines.

Postprandial bone turnover is independent of calories above 250 kcal.

BACKGROUND: The mechanisms causing bone turnover after food intake have not yet been elucidated. Several gut hormones are secreted in the postprandial phase, proportional to meal calorie content, and possibly one or more of these could influence bone turnover. The aim of this study was to investigate bone turnover in proportion to graded-calorie and fixed calcium containing meals. METHODS: A group of healthy volunteers were given six meals with calories varying from 250 to 3000 kcal on different occasions. All the meals contained 500 mg of calcium. C-telopeptide type I collagen (CTX) was measured before and 180 min after each meal. RESULTS: All meals significantly reduced CTX between 35.8 +/- 5.6% and 44.8 +/- 3.8%. No significant difference in CTX was however apparent for the different calorie containing meals. Observed differences suggest a trend to greater CTX suppression with lower protein and higher fat content of meals. CONCLUSION: Changes in CTX are not proportional to calorie contents when the meals contain 500 mg of calcium. Further studies should now determine whether patients with increased bone resorption would benefit from multiple small meals to slow down the rate of bone loss.