Serena Torraca

Acute Effects of Very-Low-Protein Diet on FGF23 Levels: A Randomized Study

BACKGROUND AND OBJECTIVES High levels of fibroblast growth factor 23 are associated with mortality, CKD progression, and calcification in CKD patients. The aim of this pilot study is to assess whether a very-low-protein diet (0.3 g/kg per day) with a consequent low intake of phosphorus would reduce fibroblast growth factor 23 compared with a low-protein diet (0.6 g/kg per day) in CKD patients not yet on dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A prospective, randomized, controlled crossover study was performed in which 32 patients were randomized into two groups. Group A (16 patients) received a very-low-protein diet (0.3 g/kg body wt per day) supplemented with ketoanalogues during the first week and a low-protein diet during the second week, and group B (16 patients) received a low-protein diet during the first week and a very-low-protein diet during the second week. Fibroblast growth factor 23, seric, and urinary phosphate levels were measured at baseline and the end of each study period. RESULTS After only 1 week of the very-low-protein diet, reductions in fibroblast growth factor 23 levels (33.5%), serum phosphate (12%), and urinary phosphate (34%) with the very-low-protein diet compared with the low-protein diet were observed. Serum and urinary phosphate levels and protein intake were significant determinants of fibroblast growth factor 23 (95% confidence interval=1.04-1.19, 1.12-1.37, and 1.51-2.23, respectively). CONCLUSIONS A very-low-protein diet supplemented with ketoanalogues reduced fibroblast growth factor 23 levels in CKD patients not yet on dialysis.

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.

Coronary Artery Calcification Progression Is Associated with Arterial Stiffness and Cardiac Repolarization Deterioration in Hemodialysis Patients

Background/Aims: Evidence suggests that vascular calcification (VC) portends poor cardiovascular (CV) prognosis in patients undergoing maintenance dialysis (CKD-5). Nonetheless, how VC might predispose to CV mortality still remains to be clarified. Herein, we report on the association between coronary artery calcification (CAC) progression and changes in cardiac repolarization as well as arterial stiffness. Methods: 132 patients new to dialysis were identified. Demographic and clinical characteristics were collected at study entry and during the 12-month follow-up. CAC, 12-lead ECG and pulse wave velocity (PWV) were assessed at baseline and study completion. Uni- and multivariable analyses were applied to detect factors associated with worsening of cardiac repolarization (QTd) and arterial stiffness (PWV). Results: Uni- and multivariable analyses revealed that CAC progression was associated with a significant increase in both QTd and PWV. Every 20-unit increase in the CAC score corresponded to a significant 23% (95% CI 1.12–1.27; p < 0.001) and 32% (95% CI 1.09–1.37; p < 0.01) increase in the risk of experiencing a 1-m/s increase in PWV and 1 ms in QTd, respectively. Conclusion: VC is a marker of vasculopathy and appears to be associated with cardiac repolarization and arterial stiffness abnormalities in CKD-5 patients.

Low-protein diets for chronic kidney disease patients: the Italian experience

BackgroundNutritional treatment has always represented a major feature of CKD management. Over the decades, the use of nutritional treatment in CKD patients has been marked by several goals. The first of these include the attainment of metabolic and fluid control together with the prevention and correction of signs, symptoms and complications of advanced CKD. The aim of this first stage is the prevention of malnutrition and a delay in the commencement of dialysis. Subsequently, nutritional manipulations have also been applied in association with other therapeutic interventions in an attempt to control several cardiovascular risk factors associated with CKD and to improve the patients overall outcome. Over time and in reference to multiple aims, the modalities of nutritional treatment have been focused not only on protein intake but also on other nutrients.DiscussionThis paper describes the pathophysiological basis and rationale of nutritional treatment in CKD and also provides a report on extensive experience in the field of renal diets in Italy, with special attention given to approaches in clinical practice and management.SummaryItalian nephrologists have a longstanding tradition in implementing low protein diets in the treatment of CKD patients, with the principle objective of alleviating uremic symptoms, improving nutritional status and also a possibility of slowing down the progression of CKD or delaying the start of dialysis. A renewed interest in this field is based on the aim of implementing a wider nutritional therapy other than only reducing the protein intake, paying careful attention to factors such as energy intake, the quality of proteins and phosphate and sodium intakes, making today’s low-protein diet program much more ambitious than previous. The motivation was the reduction in progression of renal insufficiency through reduction of proteinuria, a better control of blood pressure values and also through correction of metabolic acidosis. One major goal of the flexible and innovative Italian approach to the low-protein diet in CKD patients is the improvement of patient adherence, a crucial factor in the successful implementation of a low-protein diet program.

Setting dialysis start at 6.0 ml/min/1.73 m2 eGFR—a study on safety, quality of life and economic impact

BACKGROUND End-stage renal disease care requires enormous economic resources. A timely dialysis start could reduce the costs of the renal replacement therapy (RRT). Our aim was to measure the time to dialysis in CKD patients, with an estimated glomerular filtration rate (eGFR) <or=11.0 ml/min/1.73 m(2) (MDRD derived), and to evaluate the safety, economic impact and the quality of life (QoL). METHODS In a prospective, observational study, 70 consecutive CKD patients, stage 5, were screened and 30 patients were selected and followed up monthly, for 24 months or until the start of RRT, set at an eGFR = 6.0 ml/min/ 1.73 m(2) or at the occurrence of pre-defined urgent criteria. The SF-36 questionnaire to evaluate the QoL was performed at the first and the last visit. RESULTS The median time to the start of dialysis was 11.8 (25th and 75th: 5.5-17.3) months. Only seven patients urgently started dialysis, after 8 months (25th and 75th: 4.8-20). The mean monthly cost of care was euro 1146 +/- 917 per patient. The QoL was similar to that of the general population and did not change at the last assessment. Discussion. This is the first study evaluating the economic impact of intensive conservative management of CKD stage 5 to postpone start of dialysis in tertiary care. This strategy allows us to safely gain a significant amount of time free from dialysis, with good QoL and major savings in the costs of nations dialysis budget. The present results, however, are applicable only to low comorbidity patients referred to nephrology care and may not be generalized to all patients starting RRT.

Daily dialysis reduces pulse wave velocity in chronic hemodialysis patients

Pulse wave velocity (PWV) is a predictor of morbidity and mortality in patients with end-stage renal disease (ESRD). Dialysis patients show cyclic changes in PWV related to their hydration status and blood pressure. Our aim is to assess the impact of daily dialysis on PWV. We performed a randomized crossover study of 60 patients who underwent standard hemodialysis (HD) three times per week for at least 6 months. Patients were classified into three groups according to their PWV values before (pre-) and after (post-) HD, with a cutoff value of 12 m s−1, as follows: the low–low (LL) group had normal pre-HD and post-HD PWV; the high–low (HL) group had high pre-HD PWV and normal post-HD PWV; and the high–high (HH) group had high pre- and post-HD PWV. All patients continued standard HD for 2 weeks. A total of 10 patients from each group were randomly assigned to continue standard HD for 1 week and then underwent daily dialysis for 1 week. The remaining 10 patients underwent daily dialysis for 1 week and then underwent standard HD for 1 week. PWV values were measured before and 1 h after each dialysis session. With daily dialysis treatment, 2 of 20 patients (10%) moved from the PWV–HH group to the PWV–HL group, whereas 18 of 20 patients (90%) moved from the PWV–HL group to the PWV–LL group (P=0.030). Daily dialysis reduces PWV in the ESRD patients. As PWV is a strong predictor of mortality in ESRD and has cyclic variations in patients who are on standard HD, we believe that daily dialysis may be used in patients with high PWV levels to reduce their mortality risk.

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.

Controversial issues in CKD clinical practice: position statement of the CKD-treatment working group of the Italian Society of Nephrology

This position paper of the study group “Conservative treatment of Chronic Kidney Disease—CKD” of the Italian Society of Nephrology addresses major practical, unresolved, issues related to the conservative treatment of chronic renal disease. Specifically, controversial topics from everyday clinical nephrology practice which cannot find a clear, definitive answer in the current literature or in nephrology guidelines are discussed. The paper reports the point of view of the study group. Concise and practical advice is given on several common issues: renal biopsy in diabetes; dual blockade of the renin–angiotensin–aldosterone system (RAAS); management of iron deficiency; low protein diet; dietary salt intake; bicarbonate supplementation; treatment of obesity; the choice of conservative therapy vs. dialysis. For each topic synthetic statements, guideline-style, are reported.

Does Brachial Blood Pressure Need to Predict Cardiovascular Outcomes in End Stage Renal Disease? An Update

Hypertension is responsible for a significantly increased burden of cardiovascular events and it is cause and a consequence of Chronic Kidney Disease (CKD) and a determinant factor in its progression to End Stage Kidney Disease (ESKD). Therefore, nephrologists have been focusing their attention on hypertension control to prevent CKD progression, delaying it but with poor results on cardiovascular mortality reduction. An important effect is the difficulty to adequately reduce BP levels in CKD patients and especially in dialysis patients despite the polipharmacological therapy. We have to take into account other aspects influencing mortality risk in CKD patients .The first aspect to consider is whether brachial blood pressure (BP) measurement is sufficient to describe the complex relationship between the alteration of BP and outcomes in renal subjects. The second aspect to consider is the variability of BP (BPV). We think that BP measurement cannot only take into account brachial BP, because it represents a limited measure of a complex clinical condition in CKD or ESRD patients. The inability to evaluate hypertension in its complexity explains why several aspects are still unrecognized.

Phosphorus, beverages, and chronic kidney disease

Phosphate is present in food in two forms, ie, organic and inorganic phosphate salts, which are naturally present in food and as phosphates added for industrial and commercial reasons. There is also a high content of added phosphate in beverages, and phosphates in this form are highly absorbable. The real content of phosphate contained in beverages is often unrecognized, and nephrologists do not always take into account the amount of phosphorus that patients ingest in this form.