[Effects of dose of erythropoiesis stimulating agents on cardiovascular outcomes, quality of life and costs of haemodialysis. the clinical evaluation of the DOSe of erythropoietins (C.E. DOSE) Trial]. / Effetti della dose degli agenti stimolanti l'eritropoiesi su esiti cardio-cerebrovascolari, qualità di vita e costi in emodialisi.

BACKGROUND: Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested. METHODS: We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).

[Cystatin C, beta2-microglobulin and C-reactive protein in hemodiafiltration and on-line endogenous liquid reinfusion and in low flux polysulphone bicarbonate conventional hemodialysis]. / Cistatina C, beta2-microglobulina e proteina C-reattiva in emodiafiltrazione con reinfusione on-line (HFR) e in bicarbonato dialisi con polisulfone low-flux (BD).

PURPOSE: Dialysis morbidity results partly from middle and large molecule retention, which is poorly removed by conventional hemodialysis (HD). The potential benefit of convective treatments could be the enhanced toxin removal over a wide molecular weight spectrum. This study aimed to evaluate cystatin C (cis), beta2-microglobulin (beta2-m) and C-reactive protein (CRP) removal behavior during hemodiafiltration reinfusion vs conventional low-flux HD (1.8 m2 low-flux polysulphone) (bicarbonate dialysis (BD)). The molecular weights of the substances evaluated in this study were as follows: cis = 13,300 daltons, beta2-m = 11,818 daltons, CRP = 160,000 daltons. METHODS: Twelve patients on stable HD (six males, six females), were enrolled; six patients underwent BD and six patients underwent HFR. We measured arteriovenous serum cis, beta2-m and CRP levels, in three consecutive mid-week sessions at the following periods: pre/post-dialysis and after 60 min from the beginning of the session. At 60, 120 and 180 min of HFR, we collected the ultrafiltrate for cis, beta2-m, and CRP evaluation. RESULTS: Cis, beta2-m and CRP mean values did not differ at pre-dialysis in the two groups. Pre/post- dialysis difference for cis in HFR vs BD was statistically significant (p=0.002) because cis reduced in HFR and increased in BD during the session. Beta2-m and CRP pre/post- dialysis differences in HFR vs BD were not significant. Cis clearance, measured 60 min after the beginning of the session was 34.2 +/- 20.1 mL/min in HFR and 24.8 +/- 18.4 mL/min in BD (p<0.05). beta2-m and CRP clearances did not differ among the treatments. Regarding the ultrafitrate concentrations during the HFR session, cis significantly decreased (2.5 +/- 0.6 mg/dL at 60 min and 2.0 +/- 0.4 mg/dL at 180 min; p=0.004), as well as beta2-m (21.5 +/- 12.9 mg/dL and 19.0 +/- 14.1 mg/dL, respectively; p=0.02). Ultrafiltrate CRP values, as expected, did not differ during HFR. CONCLUSIONS: This study demonstrated that cis, a middle molecule, is well depurated in HFR, while in BD it increases. Beta2-m, although better removed in the convective phase during HFR, does not demonstrate a removal difference in HFR and in BD. CRP, a large molecule, does not have significant removal. Since cis and beta2-m have almost the same molecular weight, why do they have a different depuration? We need further studies to evaluate if membranes can remove these molecules or if protein electrical charges or their stereoscopy enables their removal.

Anthropometric data, urinary sodium excretion, and isometric exercise in epidemiological study of arterial hypertension.

Relationships between cardiovascular response to isometric exercise, anthropometric data, and urinary sodium excretion were examined a group of 80 young males aged 19.7 +/- 1.3 years. Diastolic blood pressure (DBP) was well correlated with the anthropometric data both at rest and during hand grip (HG). During hand grip even the systolic blood pressure (SBP) was correlated with height, arm circumference, body weight, and body index. There was no significant correlation between urinary excretion of sodium and BP. The correlation between SBP and some anthropometric measures found during hand grip but not at rest suggests that the sympathetic nervous system may play a role in determining a relationship between excessive body weight and blood pressure increase.

Oxalate depuration during biofiltration with AN69 and in conventional hemodialysis in chronic renal failure (CRF) patients.

Oxalate (Ox), an end product of amino acid metabolism, accumulates in CRF patients as calcium crystal deposits in many soft tissues such as myocardium, kidney interstitium, etc. Since BF employs AN69, a high efficiency membrane, we tested its depurative efficacy for Ox against a hollow-fiber cuprophan dialyzer. Five CRF patients previously in HD and after six months of BF were studied. End-dialysis and pre-dialysis Ox values and dialyzer clearance were obtained. Predialysis Ox values were: 0.44 +/- 0.15 mg/dl in HD and 0.42 +/- 0.09 mg/dl in BF (NS). End-dialysis Ox values were: 0.30 +/- 0.09 mg/dl in HD and 0.22 +/- 0.04 mg/dl in BF (p less than 0.001). Pre and post dialysis values differed by 31% in HD and 47% in BF (p less than 0.001). Ox clearance was 98.8 +/- 10.3 ml/min in HD and 143 +/- 20.5 ml/min in BF. There was a rebound in Ox values at 48 hours (0.41 +/- 0.08 mg/dl in HD and 0.32 +/- 0.12 mg/dl in BF, (NS). These results indicate that Ox is depurated better during BF than during HD.