[A short report: Blood pressure variability and outcomes in chronic kidney disease long survivors patients]. / Short report: la variabilità della pressione arteriosa influenza la mortalità cardiovascolare e la morte renale in pazienti con Chronic Kidney Disease (CKD) and long survivors.

In the last decade blood pressure variability (BPV) measured during a follow-up of hypertensive chronic kidney disease (CKD) patients or hemodialysis patients has received a even major attention. The aim of our study is to study the relationship between BPV and mortality and/or dialysis initiation in long survivors CKD patients. We conducted a historical prospective observational multicentric study in 131 subjects still alive at 31st December 2010, when ended a our previous study published on Nephrology Dialysis Transplantation. Long Survivors patients were younger (p<0.01) and had a lower BPV compared to the original population. Moreover, they had creatinine levels significantly lower (p<0.019), so as lower phosphate levels (p<0.05) and higher hemoglobin (p<0.05). During a mean follow-up of 80.713.4 months, 63 patients (48.1%) died and 49 of them (37.4%) started dialysis treatment. In this group, 28 patients died after dialysis initiation. Kaplan-Meier curves showed a significant association between BPV and cardiovascular mortality risk (Hazard Ratio [HR]: 1.061; 95% Confidence Interval [CI]: 1.0351.093; p = 0.001) and between BPV and renal death (HR 1.049; 95% CI: 10121.74; P = 0.001). In conclusions, our data in long survivors patients showed that BPV can be used for mortality cardiovascular and renal death risk stratification in CKD patients.

Variability of blood pressure in dialysis patients: a new marker of cardiovascular risk.

BACKGROUND: Hemodialysis patients have a high cardiovascular mortality, and hypertension is the most prevalent treatable risk factor. We aimed to assess the predictive significance of dialysis-to-dialysis variability in blood pressure in hemodialysis patients. METHODS: We performed a historical cohort study in 1,088 prevalent hemodialysis patients, followed up for 5 years. The risk of cardiovascular death was determined in relation to dialysis-to-dialysis variability in blood pressure, maximum blood pressure and pulse pressure. RESULTS: Variability in blood pressure was a predictor of cardiovascular death (hazard ratio [HR] = 1.242; 95% confidence interval [95% CI], 1.004-1.537; p=0.046). Also age (HR=1.021; 95% CI, 1.011-1.048; p=0.049), diabetes (HR=1.134; 95% CI, 1.128-1.451; p=0.035), creatinine (HR=0.837; 95% CI, 0.717-0.977; p=0.024) and albumin (HR=0.901; 95% CI, 0.821-0.924; p=0.022) influenced mortality. Maximum blood pressure and pulse pressure did not show any effect on cardiovascular death. CONCLUSION: Dialysis-to-dialysis variability in blood pressure is a predictor of cardiovascular mortality in hemodialysis patients, and blood pressure variability may be used in managing hypertension and predicting outcomes in dialysis patients.

Blood pressure variability and outcomes in chronic kidney disease.

BACKGROUND: We investigated the effects of visit-to-visit systolic blood pressure variability (SBPV) on both mortality and dialysis inception in a cohort of chronic kidney disease (CKD) patients not requiring dialysis therapy. Furthermore, we also explored the carry-over effect of visit-to-visit SBPV on mortality after dialysis initiation. METHODS: We conducted a longitudinal retrospective, observational, multi-centre study in three tertiary care nephrology outpatient clinics. All the ambulatory CKD patients admitted to the outpatient clinics from 1 January 2004 to 31 December 2005 were screened for study eligibility. We selected all consecutive patients older than 18 years of age with a mean estimated glomerular filtration rate of <60 mL/min/m(2), free from cardiovascular disease. SBPV was defined as the ratio of the SD to the mean SBP of five values recorded during a run-in phase of 4-5 months. Data on dialysis inception and mortality were recorded through 31 December 2010. RESULTS: Overall, we selected a cohort of 374 elderly (median age: 79 years) subjects. A total of 232 (62%) and 103 (29%) patients were male and had diabetes, respectively. A significant association between SBPV and the risk of death but not of CKD progression to dialysis was noted at univariate and after multivariable adjustments (hazard ratio for all-cause mortality per 1% increase in SBPV: 1.05; 95% confidence interval: 1.02-1.09; P = 0.001). Notably, no lethal event was recorded after dialysis initiation. CONCLUSIONS: Current findings suggest that SBPV may be of use for risk stratification in CKD patients.

Fate of eprinomectin in goat milk and cheeses with different ripening times following pour-on administration.

The distribution of eprinomectin in goat milk and cheeses (cacioricotta, caciotta, caprilisco) with different ripening times following a pour-on administration at a single dose rate (500 microg/kg of body weight) and a double dose rate (1,000 microg/kg of body weight) to goats with naturally occurring infections of gastrointestinal nematodes was studied. Milk residues of eprinomectin reached a maximum of 0.55+/-0.18 microg/kg and 1.70+/-0.31 microg/kg at the single and double doses, respectively. The drug concentrations decreased progressively until the fifth day after treatment, when they were less than the detection limit at both dose rates. The eprinomectin levels measured in all cheese types (both treatments) were higher than those recovered in milk at all the sampling times. In caciotta cheeses, the eprinomectin residues levels were constantly higher than other cheeses. With the exception of cheeses made with milk the first day after treatment, eprinomectin concentrations were nearly constant up to the fourth day then decreased by the fifth and sixth days after treatment. In all cases, at both the single and double dosages, the maximum level of eprinomectin residues in goat milk and cheeses remained below the maximum residual level of 20 microg/liter permitted for lactating cattle.

Efficacy of erythropoietin on dialysis in patients with beta thalassemia minor.

BACKGROUND: It is unknown whether chronic erythropoietin (EPO) treatment is able to normalize hemoglobin (Hb) levels and ameliorate cardiac remodeling avoiding blood transfusions in uremic blood transfusion-dependent patients with beta-thalassemia minor (beta-thal). METHODS: In 12 hemodialysis (HD) patients with beta-thal, requiring blood transfusions despite EPO therapy, we planned to increase Hb levels up to the target levels (11-12 g/dl) within a one-year period by administering progressively higher doses of EPO (correction phase). We also planned to maintain the Hb target for an additional year (maintenance phase). RESULTS: In the year before the study, patients required 3.3 +/- 0.9 units of packed red blood cells. At baseline, the Hb level obtained with an EPO dose of 212 +/- 73 U/kg/week i.v. was 8.2 +/- 0.8 g/dl. The EPO dose was gradually increased within the first year up to 458 +/- 78 U/kg/week at month 12 (correction phase) and then significantly tapered down during the maintenance phase (390 +/- 54 U/kg/week at month 24). During the correction phase, the Hb levels markedly increased (11.1 +/- 0.3 g/dl at month 12) and did not change in the maintenance phase. No blood transfusion was required throughout the 2 years of follow-up. Left ventricular (LV) mass index progressively decreased from the basal value of 144 +/- 12 to 124 +/- 11 g/m2 in the first year and normalized in all patients at month 24 (109 +/- 12 g/m2, p < 0.001); this occurred in the absence of any change of LV cavity volume index (<90 ml/m2). CONCLUSIONS: In HD transfusion-dependent patients with beta-thal, the administration of high EPO dose for 2 years permits the attainment and the maintenance of Hb targets without blood transfusions. This therapeutic approach permits a complete remission of concentric LV hypertrophy without any adverse effects on the vascular system.

Intra- and post-dialytic changes of haemoglobin concentrations in non-anaemic haemodialysis patients.

BACKGROUND: Non-anaemic haemodialysis (HD) patients are potentially more prone to the adverse effects of ultrafiltration-induced haemoconcentration. No study, however, has assessed the effects of dialytic session on haemoglobin (Hb) levels in these patients. METHODS: The levels of Hb and total protein before, at the end (T0) and up to 120 min (T120) after the third HD session of the week were compared in non-anaemic (Hb >13 g/dl, n = 14, NOR) and anaemic (Hb = 11-12 g/dl, n = 18, LOW) HD patients. RESULTS: The intradialytic weight loss was similar in the two groups (4.0 +/- 0.9 and 4.1 +/- 0.9% body weight). During the treatment, Hb levels increased to the same extent in both groups (from 14.4 +/- 1.2 to 16.3 +/- 1.9 g/dl in NOR, and from 11.4 +/- 0.8 to 12.7 +/- 0.9 g/dl in LOW) in the presence, presumably, of a smaller plasma volume in NOR, whereas the increment of total protein was greater in NOR (from 7.1 +/- 0.2 to 9.6 +/- 0.5 g/dl) than in LOW (from 7.3 +/- 0.6 to 8.7 +/- 0.8 g/dl) (P < 0.0001). At T120, the Hb decline in NOR was almost double that measured in LOW (-9.2 +/- 3.0 vs -4.7 +/- 2.4%, P < 0.001). Consequently, Hb concentration did not differ from the pre-dialytic value in NOR (P = 0.10), but persisted higher in LOW (P < 0.005). The extent of the post-dialytic decrement of Hb was inversely related to the total protein values at T0 (r = -0.547, P = 0.0012). CONCLUSIONS: This study indicates that in NOR: (i) the extent of intradialytic increment of Hb is limited by a greater intradialytic plasma refilling; (ii) the greater plasma refilling persists after the end of dialysis, with the restoration of pre-dialytic Hb levels within the initial 2 h; and (iii) the force driving this phenomenon resides mainly in the larger changes of total protein concentration.

Supplemented very low protein diet ameliorates responsiveness to erythropoietin in chronic renal failure.

BACKGROUND: The aim of this study was to evaluate the relationship between uremic state and erythropoiesis in patients with predialytic chronic renal failure (CRF). METHODS: We monitored for 2 years the erythropoietin (EPO) requirement in patients with advanced CRF (creatinine clearance < or =25 mL/min), randomized to either low protein diet (LPD) group (0.6 g/kg body weight/day, N = 10) or very low protein diet (VLPD) group (0.3 g/kg body weight/day, N = 10) supplemented with a mixture of ketoanalogs and essential amino acids, both kept at target hemoglobin levels. RESULTS: The achieved protein intake after 6 months was 0.79 +/- 0.02 g/kg body weight/day and 0.50 +/- 0.02 g/kg body weight/day in LPD and VLPD, respectively; such a difference was maintained up to the end of follow up. The final hemoglobin values did not differ from the basal values in either group (11.5 +/- 0.2 g/dL and 11.5 +/- 0.3 g/dL). EPO dose, that was similar at baseline (62.4 +/- 9.6 UI/kg body weight/week and 61.8 +/- 8.8 UI/kg body weight/week subcutaneously), remained unchanged in LPD but progressively decreased in VLPD down to the final value of 41.2 +/- 7.0 UI/kg body weight/week (P < 0.0001 vs. basal and LPD). VLPD was associated with a decrease of urinary excretion and serum levels of urea nitrogen and phosphate; however, EPO requirement was not correlated with the changes of these parameters. On the contrary, the variation of EPO dose directly correlated with the modification of parathyroid hormone (PTH) levels, that diminished from 229 +/- 55 pg/mL to 118 +/- 16 pg/mL (P < 0.0001) in VLPD and did not change in LPD. CONCLUSION: In patients with advanced CRF, an effective decrease of protein intake of 0.3 g/kg body weight/day induces a reduction of about 35% of the EPO dose required to maintain the target hemoglobin levels. This effect appears dependent on the correction of a moderate secondary hyperparathyroidism.