Correction to: Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study.

It occurred to us that a simple but significant calculation error was made in Table 2 in the dose of bicarbonate administered. Indeed, contrary to what reported in Table 2, the dose of sodium bicarbonate administered during study was.

Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study.

BACKGROUND: Metabolic acidosis is associated with accelerated progression of chronic kidney disease (CKD). Whether treatment of metabolic acidosis with sodium bicarbonate improves kidney and patient survival in CKD is unclear. METHODS: We conducted a randomized (ratio 1:1). open-label, controlled trial (NCT number: NCT01640119. www.clinicaltrials.gov ) to determine the effect in patients with CKD stage 3-5 of treatment of metabolic acidosis with sodium bicarbonate (SB) on creatinine doubling (primary endpoint), all-cause mortality and time to renal replacement therapy compared to standard care (SC) over 36-months. Parametric, non-parametric tests and survival analyses were used to assess the effect of SB on these outcomes. RESULTS: A total of 376 and 364 individuals with mean (SD) age 67.8 (14.9) years, creatinine clearance 30 (12) ml/min, and serum bicarbonate 21.5 (2.4) mmol/l were enrolled in SB and SC, respectively. Mean (SD) follow-up was 29.6 (9.8) vs 30.3 (10.7) months in SC and SB. respectively. The mean (SD) daily doses of SB was 1.13 (0.10). 1.12 (0.11). and 1.09 (0.12) mmol/kg*bw/day in the first, second and third year of follow-up, respectively. A total of 87 participants reached the primary endpoint [62 (17.0%) in SC vs 25 (6.6%) in SB, p < 0.001). Similarly, 71 participants [45 (12.3%) in SC and 26 (6.9%) in SB, p = 0.016] started dialysis while 37 participants [25 (6.8%) in SC and 12 (3.1%) in SB, p = 0.004] died. There were no significant effect of SB on blood pressure, total body weight or hospitalizations. CONCLUSION: In persons with CKD 3-5 without advanced stages of chronic heart failure, treatment of metabolic acidosis with sodium bicarbonate is safe and improves kidney and patient survival.

Correction of metabolic acidosis improves insulin resistance in chronic kidney disease.

BACKGROUND: Correction of metabolic acidosis (MA) with nutritional therapy or bicarbonate administration is widely used in chronic kidney disease (CKD) patients. However, it is unknown whether these interventions reduce insulin resistance (IR) in diabetic patients with CKD. We sought to evaluate the effect of MA correction on endogenous insulin action in diabetic type 2 (DM2) CKD patients. METHODS: A total of 145 CKD subjects (83 men e 62 women) with DM2 treated with oral antidiabetic drugs were included in the study and followed up to 1 year. All patients were randomly assigned 1:1 to either open-label (A) oral bicarbonate to achieve serum bicarbonate levels of 24-28 mmol/L (treatment group) or (B) no treatment (control group). The Homeostatic model assessment (HOMA) index was used to evaluate IR at study inception and conclusion. Parametric and non-parametric tests as well as linear regression were used. RESULTS: At baseline no differences in demographic and clinical characteristics between the two groups was observed. Average dose of bicarbonate in the treatment group was 0.7 ± 0.2 mmol/kg. Treated patients showed a better metabolic control as confirmed by lower insulin levels (13.4 ± 5.2 vs 19.9 ± 6.3; for treated and control subjects respectively; p < 0.001), Homa-IR (5.9[5.0-7.0] vs 6.3[5.3-8.2]; p = 0.01) and need for oral antidiabetic drugs. The serum bicarbonate and HOMA-IR relationship was non-linear and the largest HOMA-IR reduction was noted for serum bicarbonate levels between 24 and 28 mmol/l. Adjustment for confounders, suggests that serum bicarbonate rather than treatment drives the effect on HOMA-IR. CONCLUSIONS: Serum bicarbonate is related to IR and the largest HOMA-IR reduction is noted for serum bicarbonate between 24 and 28 mmol/l. Treatment with bicarbonate influences IR. However, changes in serum bicarbonate explains the effect of treatment on HOMA index. Future efforts are required to validate these results in diabetic and non-diabetic CKD patients. TRIAL REGISTRATION: The trial was registered at www.clinicaltrial.gov (Use of Bicarbonate in Chronic Renal Insufficiency (UBI) study - NCT01640119 ).

Quality of life of hemodialysis patients in Central and Southern Italy: cross-sectional comparison between Hemodiafiltration with endogenous reinfusion (HFR) and Bicarbonate Hemodialysis.

INTRODUCTION: in hemodialysis (HD) patients, poor health-related quality of life (HR-QoL) is prevalent and associated with adverse outcomes. HR-QoL is strictly linked to nutritional status of HD patients. Hemodiafiltration with endogenous reinfusion (HFR) is an alternative dialysis technique that combines diffusion, convection and absorption. It reduces burden of inflammation and malnutrition and this effect may cause beneficial effect on HR-QoL. However no data on HR-QoL in HFR is currently available. METHODS: we designed a cross-sectional multicentre study in order to compare the HR-QoL in patients treated with HFR versus Bicarbonate HD (BHD). We enrolled adult patients HFR treated for at least 6 months, with life expectancy greater than six months and without overt cognitive deficit. The recruited patients in HFR were matched for age, gender, dialytic vintage and performance in activities of daily living (Barthel index) with BHD treated patients. SF-36 questionnaire for the assessment of HR-QoL was administered. RESULTS: one hundred fourteen patients (57 HFR vs 57 BHD) were enrolled (age 65.413.5 years; dialysis vintage 5.4 (3.3-10.3) years; 53% males) from 18 dialysis non-profit centres in central and southern Italy. As result of matching, no difference in age, gender, dialytic age and Barthel index was found between HFR and BHD patients. In HFR patients we observed better values of physical component score (PCS) of SF-36 than BHD patients (P=0.048), whereas no significant difference emerged in the mental component score (P=0.698). In particular HFR patients were associated with higher Physical Functioning (P=0.045) and Role Physical (P=0.027). CONCLUSIONS: HFR is associated with better physical component of HR-QoL than BHD, independently of age, gender, dialysis vintage and invalidity score. Whether these findings translate into a survival benefit must be investigated by longitudinal studies.

[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.

Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic chronic inflammation in maintenance hemodialysis patients: a multicenter longitudinal study.

Chronic inflammation is widely diffuse in maintenance hemodialysis (MHD) patients and is associated with poor survival. Hemodiafiltration with endogenous reinfusion (HFR) is a dialysis technique, highly biocompatible, able to adsorb proinflammatory cytokines and to decrease amino acids and antioxidants loss. These features could be helpful in MHD patients affected by idiopathic chronic inflammation, but this issue remains to be elucidated. We performed a multicenter longitudinal study to assess the effect of the switching from bicarbonate HD to HFR in patients with serum C-reactive Protein (CRP) > 5 mg/L coupled with albumin <4.0 g/dL in the last 6 months. We enrolled 24/176 (14%) patients, of which 20 patients were assessed at 4 months and 18 completed the study. We excluded 11 patients with evident causes of inflammation. At baseline, serum levels of CRP (18.7[7.0-39.4] mg/L) and albumin (3.5[3.3-3.7] g/dL) were significantly correlated (r = -0.49; P = 0.028). The effect on CRP and albumin was almost evident in the first 4 months and remained stable until to eighth month. A strict correlation (R = -0.49; 0.040) between percentage change of CRP (-35%) and albumin (+14%) after 8 months of HFR. These effects were associated with the reduction of IL-6, IL-1ß, and TNF-α and the increment of pre-albumin and leptin, whereas the serum levels of Branched Chain Amino Acid (BCAA) remained unchanged. In MHD patients affected by idiopathic chronic inflammation the switching from BHD to HFR is associated with improvement of inflammation. Whether these favorable effects may modify the outcomes of these high-risk patients needs to be confirmed by studies ad hoc.

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.

Variability of pulse wave velocity and mortality in chronic hemodialysis patients.

We have already demonstrated that in chronic hemodialysis (HD) patients, the cyclic variations in both hydration status and blood pressure are responsible for changes in pulse wave velocity (PWV). The aim of this study is to verify whether the cyclic variation of PWV influences mortality in dialysis patients. We studied 167 oligoanuric (urinary output <500 mL/day) patients on chronic standard bicarbonate HD for at least 6 months. They performed 3 HD sessions of 4 hours per week. Patients were classified into 3 groups: normal PWV before and after dialysis (LL); high PWV before and normal PWV after dialysis (HL); and high PWV before and after dialysis (HH). The carotid-femoral PWV was measured with an automated system using the foot-to-foot method. Analysis of variance was used to compare the different groups. The outcome event studied was all-cause mortality and cardiovascular mortality. The PWV values observed were LL in 44 patients (26.3%); HL in 53 patients (31.8%); and HH in 70 patients (41.9%). The 3 groups of patients are homogenous for sex, age, and blood pressure. The HH group had a higher prevalence of (P<0.001) ASCVD. It is interesting that the distribution of patients in the 3 groups is correlated with the basal value of PWV. In fact, when the basal measure of PWV is elevated, there is a higher probability that an HD session cannot reduce PWV (<12 ms). A total of 53 patients (31.7%) died during the follow-up of 2 years: 5 patients in the LL group (11.4%); 16 in the HL group (30.2%); and 32 in the HH group (50.7%) (LL vs. HL, P=0.047; LL vs. HH, P<0.00001; HL vs. HH, P=0.034). We evidence for the first time that different behaviors of PWV in dialysis subjects determine differences in mortality.

Long-term L-carnitine administration reduces erythropoietin resistance in chronic hemodialysis patients with thalassemia minor.

BACKGROUND AND AIM: Both thalassemia and carnitine deficiency represent independent causes of erythropoietin resistance, and thus anemia, in uremic patients. We evaluated the unknown long-term effects of L-carnitine administration in ß-thalassemic on chronic hemodialysis. METHODS: We studied twelve subjects (M = 8; F = 4) affected by ß-thalassemia minor (ß-thal; HbA2 level = 6.6 ± 0.6%) and forty non-thalassemic subjects (M = 24; F = 16) as controls (C), on chronic hemodialysis treatment. Patients and controls were at target hemoglobin levels (11-12g/dl) prior to the study and underwent to i.v. L-carnitine administration for a one year period-time. RESULTS: Groups were comparable for age, gender, serum levels of hemoglobin (Hb), iron, ferritine, PTH and aluminum, transferrin saturation, and dialysis modalities. During the study both groups showed significant Hb increase and erythropoietin (EPO) decrease; as a difference, such changes emerged at the 3rd month in C but at the 8th month in ß-thal. At start, during the dialysis session the erythrocyte MCV reduced in C but not in ß-thal (65.3 ± 3.2 to 65.5 ± 3.2 fl; NS); along carnitine administration period, however, MCV during dialysis decreased also in ß-thal, starting since the 9th month of treatment. CONCLUSION: This study provides evidence of the lowering of EPO resistance in ß-thalassemia patients on hemodialysis due to long-term carnitine administration. Thus, prolonged carnitine supplementation should be suggested to patients on dialysis affected by ß-thalassemia with poorly responsive anemia, or requiring large doses of erythropoietin.

Relationship between resistance to erythropoietin and high anomalous hemoglobin levels in hemodialysis patients with beta-thalassemia minor.

In dialysis patients beta-thalassemia is a cause of resistance to erythropoietin (EPO). The aim of the present study is to evaluate the relationship between the amount of circulating anomalous hemoglobin chain and EPO resistance in hemodialysis. Ten hemodialyzed patients with beta-thalassemia minor were studied. The mean hemoglobin level was 9.22 +/- 0.91 g/dl, the HbA2 ranging between 5.6 and 6.8%; the weekly EPO dose was 13,500 +/- 7,185 IU/week and significantly correlated with HbA2 (r = 0.965; p = 0.0001). When stratifying patients in two groups according to HbA2 level (LOW <6%, n = 4; HIGH >6%, n = 6; HbA2 levels, respectively, 5.7 +/- 0.1 and 6.4 +/- 0.3 g/dl, p = 0.002), it was evidenced that the need of EPO was 13,200 +/- 3,033 IU/week in LOW and 36,167 +/- 13,060 IU/week in HIGH (p < 0.001). The EPO Resistance Index in the two groups was 13.4 +/- 4.1 IU/kg BW/week/g Hb in LOW and 21.9 +/- 10.0 in HIGH (p < 0.05). No differences were evidenced between the two groups regarding age, dialysis, body weight, serum levels of urea nitrogen, creatinine, albumin, C-reactive protein, aluminum, ferritin, transferrin and parathyroid hormone. In conclusion, in patients with beta-thalassemia minor on chronic hemodialysis, the amount of anomalous hemoglobin chain directly correlate with EPO dose, strongly indicating the magnitude of resistance to erythropoietin.