ABSTRACT
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.
Subject(s)
Antimicrobial Cationic Peptides/blood , GPI-Linked Proteins/blood , Kidney Failure, Chronic/blood , Renal Insufficiency, Chronic/blood , Adult , Aged , Case-Control Studies , Female , Ferritins/blood , Hemochromatosis Protein , Hepcidins , Humans , Kidney Transplantation , Male , Middle Aged , Renal DialysisABSTRACT
Acute kidney injury is common and carries a high mortality. Many drugs have been evaluated for their role in preventing acute kidney injury, of which some are of no benefit and others may be harmful. This review discusses current interventions to prevent acute kidney injury and reviews the evidence base for each.
Subject(s)
Acute Kidney Injury/prevention & control , Glomerular Filtration Rate/physiology , Renal Circulation/physiology , Acetylcysteine/therapeutic use , Acute Kidney Injury/etiology , Acute Kidney Injury/physiopathology , Allopurinol/therapeutic use , Aminoglycosides/adverse effects , Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Contrast Media/adverse effects , Dehydration/complications , Dehydration/prevention & control , Dopamine Agonists/therapeutic use , Humans , Hypovolemia/complications , Hypovolemia/prevention & control , Natriuretic Peptides/therapeutic use , Renal Agents/therapeutic use , Sodium Potassium Chloride Symporter Inhibitors/adverse effects , Theophylline/therapeutic useABSTRACT
BACKGROUND: Elevated pulse pressure (PP) is an indicator of poor outcome in hypertensives in the general population and on haemodialysis. The prognostic value of PP in pre-dialysis patients with chronic kidney disease (CKD) stages 4/5 and its interaction with renin-angiotensin system (RAS) inhibitors is unknown. METHODS: This retrospective study of 349 patients from the pre-dialysis clinic analysed the effect association of PP and RAS inhibition on adverse outcomes in CKD stages 4/5. Primary endpoints were a composite of death or dialysis. RESULTS: At baseline, 349 patients (63% males, 34% diabetics) were aged 60+/-0.8 years (mean+/-SEM) with systolic blood pressure (SBP) 149+/-1.3 mmHg, diastolic BP (DBP) 83+/-0.7 mmHg, PP 66+/- 1.0 mmHg, creatinine 442+/-16 micromol/l and haemoglobin 10.7+/-0.1 g/dl. Patients were followed up for 297+/-19 days and 93% took one to seven (2.45+/-0.07) antihypertensives. At presentation, the adverse outcome group had higher SBP (151+/-1.5 vs 145+/-2.4 mmHg; P<0.05), proportion of diabetes (39% vs 23%; P<0.05) and creatinine (478+/-22 vs 354+/-11 micromol/l; P<0.05), but lower haemoglobin (10.6+/-0.1 vs 11.2+/-0.2 g/dl; P<0.05). PP increased with age (r(2): 0.4; P<0.0001). PP >80 mmHg was associated with adverse outcome (Kaplan-Meier survival analysis, log-rank test P<0.05). In a model of proportional hazards regression, adjusted for age, baseline creatinine, diabetes and haemoglobin, elevated PP was associated with poorer outcome (hazards ratio: 1.09; 95% confidence interval: 1.01-1.18; P<0.05) and angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker use was beneficial (hazards ratio: 0.73; 95% confidence interval: 0.53-0.99; P<0.05). CONCLUSIONS: The study demonstrates that elevated PP indicates high risk of death or dialysis and the benefit of blockade of the RAS is independent of the baseline PP in patients with CKD stages 4/5.
