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[Abstract] Background. Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3–5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Methods. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. Results. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Conclusions. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event.

Although intravenous iron has proved to optimize the efficacy of EPOrHu in hemodialysis patients, hitherto no consensus exists with respect to the best regimen of intravenous iron administration. We started a prospective randomized study in 26 patients undergoing chronic hemodialysis who had adequate iron metabolism indices (serum ferritin >100 µg/l; %TSAT >20%; %HypoE 26 pg) and were in the maintenance phase of EPOrHu administration (target hemoglobin obtained >10 g/dl). All patients were receiving sodium ferric gluconate (Ferrlecit®) intermittently prior to the study and after a 1-month wash-out period where iron was not administered patients were randomized to receive the same previous dose of intravenous iron either in a continuous (6.25–21.3 mg in every hemodialysis session) or an intermittent regimen (62.5 mg every 1–4 weeks, not modifying the previous schedule of administration). At 16 weeks, the continuous group showed a significant increment in serum Hb (11.83 ± 1.12 g/dl) with respect to baseline (10.96 ± 1.31 g/dl) (p < 0.05), whereas no differences were obtained in intermittent group (baseline: 11.16 ± 1.03 g/dl; 16 weeks: 11.14 ± 0.90 g/dl, NS). In contrast with the intermittent group, serum ferritin increased significantly in the continuous group (16 weeks: 508 ± 157 µg/l; baseline: 368 ± 56 µg/l; p < 0.05), whereas %TSAT and CHr did not modified during the study in both groups. %HypoE increased significantly with respect to baseline values in the continuous group (p < 0.05) and close to significantly different in the intermittent group (p = 0.06). Our study suggests that hemodialysis patients in the maintenance phase of EPOrHu administration would obtain further benefit in terms of serum hemoglobin level with a continuous intravenous serum ferric gluconate regimen, at least in the short term.

Both senile dementia (SD) and hypertension (HBP) are pathologies with a high prevalence (Applegate, 1989; Cacabelos, 1995). SD is the third health problem in developed countries after cardiovascular disease and cancer (with a prevalence of 5–15 % after the age of 65 (Cacabelos, 1995). Hypertension is a risk factor classically associated with SD of the vascular type (Sokoog, 1994, 1996, Strandgaard, 1994). Genetic factors, and particularly Apolipoprotein E (APOE), have been associated with SD (Saunders, 1993; Basun, 1995; Cacabelos, 1996; Beyer, 1996) although no specific factors correlating SD and HBP have yet been identified.