Giuliano Brunori

Cardiovascular Comorbidity and Late Referral Impact Arteriovenous Fistula Survival: A Prospective Multicenter Study

Autologous arteriovenous fistulas (AVF) have the best 5-yr patency and the lowest complication rate among hemodialysis vascular accesses. However, maturation requirements to optimize survival are unknown. A longitudinal cohort study was conducted to ascertain risk factors for failure, maturation time, and survival of the first AVF. All patients who initiated hemodialysis between January 1, 1997, and December 31, 2002, in three centers were included in this study. Analysis was restricted to patients who received an AVF. Cox regression was used to estimate the association between predictors of interest and primary and secondary AVF survival. Of the 535 patients enrolled (mean age, 66.5 yr; 57.8% male; 26.7% diabetic), 513 (96%) received an AVF. Patients who initiated with catheters (47%) cannulated their AVF earlier (median maturation period, 0.78 versus 1.80 mo; P < 0.001). Median primary and secondary survivals were longer than 50 and 72 mo, respectively. After adjustment for confounding factors, cardiovascular disease (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.26 to 2.67), utilization earlier than 1 mo after placement (HR, 1.94; 95% CI, 1.34 to 2.82), and referral within 3 mo of dialysis start (HR, 1.55; 95% CI, 1.04 to 2.32) were associated with a reduction in primary AVF survival. Presence of cardiovascular disease (HR, 2.21; 95% CI, 1.38 to 3.55), maturation time <15 d (HR, 2.12; 95% CI, 1.20 to 3.73), and presence of catheters at hemodialysis initiation (HR, 1.79; 95% CI, 1.13 to 2.84) were associated with lower secondary AVF survival. It is concluded that cardiovascular disease, late referral, temporary catheters, and early cannulation are associated with impaired AVF survival. It is recommended that AVF be allowed to mature at least 1 mo before cannulation.

Long-term Effects of Arteriovenous Fistula Closure on Echocardiographic Functional and Structural Findings in Hemodialysis Patients: A Prospective Study

BACKGROUND The arteriovenous fistula (AVF) provides an effective vascular access for hemodialysis; however, the associated hemodynamic effects may alter cardiac structure and function. The objective of this study is to evaluate the effect of AVF closure on functional and structural echocardiographic findings. STUDY DESIGN Prospective observational study. SETTING & PARTICIPANTS In a single center between 2003 and 2006, we enrolled 25 consecutive hemodialysis patients with AVF malfunction who underwent AVF closure and conversion to a tunneled central venous catheter because of exhaustion of alternative vascular sites and 36 matched controls with a well-functioning AVF. PREDICTOR AVF closure. OUTCOMES & MEASUREMENTS Outcomes were changes in findings on echocardiograms obtained before and 6 months after AVF closure for patients in the AVF-closure group and at baseline and 6 months later for controls. Echocardiographic measurements included left ventricular (LV) internal diastolic diameter, interventricular septum thickness, diastolic posterior wall thickness, LV mass (LVM), LVM index (LVMi), and LV ejection fraction (LVEF). Dialysis modality and scheme were unchanged. RESULTS In the AVF-closure group, LVM decreased from 225 +/- 55 to 206 +/- 51 g (P < 0.001) and LVMi decreased from 135 +/- 40 to 123 +/- 35 g/m(2) (P < 0.001). LV internal diastolic diameter, interventricular septum thickness, and diastolic posterior wall thickness decreased significantly, whereas LVEF increased from 56% +/- 7% to 59% +/- 6% (P < 0.001). No significant changes were observed in controls. In patients with AVF closure, LV morphologic characteristics showed a decrease in both eccentric and concentric hypertrophy in favor of normalization or a pattern of concentric remodeling. No significant changes were observed in controls. LIMITATIONS Use of matched rather than randomized controls. CONCLUSIONS Closure of an AVF determines a significant decrease in LV internal diastolic diameter, interventricular septum thickness, and diastolic posterior wall thickness. This is associated with significant improvement in LVEF, a significant decrease in LVM and LVMi, and a more favorable shift of cardiac geometry toward normality.

The Kind of Vascular Access Influences the Baseline Inflammatory Status and Epoetin Response in Chronic Hemodialysis Patients

Background: Arteriovenous grafts (AVG) and tunneled permanent catheters (TPC) are increasingly being used in hemodialysis (HD) patients. However, their role in baseline inflammatory status has not been fully evaluated. Aim of the study was to evaluate the influence of the current kind of vascular access on the baseline inflammatory status, marked by serum C-reactive protein (CRP), and the response to epoetin therapy in a group of iron-replete HD patients, under steady clinical conditions, without evidence of acute infections and/or inflammatory diseases. Methods: We studied 79 patients who had been on bicarbonate HD for 8–410 months and were receiving epoetin therapy. They all had adequate iron stores and stable hemoglobin (Hb) levels. Exclusion criteria were fever, signs of infection, white blood cell count (WBC) >10 × 1,000/µl, for at least 4 weeks before study. 48 patients (group A) had arteriovenous fistula (AVF), 18 patients (group B) AVG, 13 patients (group C) TPC. CRP, Hb, transferrin saturation, serum ferritin, WBC, serum albumin, protein catabolic rate, Kt/V, and epoetin dose (U/kg body weight/week) were measured. CRP values were log-transformed to normalize the distribution. Results: Log-transformed CRP values among the 3 groups were significantly different: group A 1.81 ± 0.48; group B 2.12 ± 0.50, and group C 3.00 ± 0.25 (group A vs. B p < 0.003; group B vs. C p < 0.001; group A vs. C p < 0.0001). CRP and the epoetin dose were directly correlated (r = 0.519; p < 0.0001). The epoetin doses among the 3 groups were significantly different. Multiple regression analysis confirmed AVG and TPC as factors independently influencing CRP levels. Conclusions: AVG and TPC have a higher degree of chronic inflammation than AVF. The epoetin requirement is increased in TPC and AVG compared with AVF.

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.

Cost-benefit analysis of supplemented very low-protein diet versus dialysis in elderly CKD5 patients

BACKGROUND Dialysis increases patient life expectancy but is associated with clinically severe and costly complications. Health and economic benefits could derive from postponing dialysis with a supplemented very low-protein diet (sVLPD). METHODS An economic evaluation was conducted to compare benefits and costs of sVLPD versus dialysis in elderly CKD5 patients. Data from 57 patients aged >or=70 years, with glomerular filtration rate (GFR) 5-7 mL/min, previously participating in a clinical trial demonstrating non-inferior mortality and morbidity of starting sVLPD compared to dialysis treatment, were analysed: 30 patients were randomized to dialysis and 27 to sVLPD. A cost-benefit analysis was conducted, in the perspective of the National Health Service (NHS). Direct medical and non-medical benefits and costs occurring in 3.2 mean years of follow-up were quantified: time free from dialysis, cost of dialysis treatment, hospitalization, drugs, laboratory/instrumental tests, medical visits and travel and energy consumption to receive dialysis. Prices/tariffs valid in 2007 were used, with an annual discount rate of 5% applied to benefits and costs occurring after the first year. Sensitivity analyses were conducted to identify how estimates could vary in different contexts of applications. Results are reported as net benefit, expressed as mean euro/patient (patient-year). RESULTS The opportunity to safely postpone initiation of dialysis of 1 year/patient on average translated into an economic benefit to the NHS, corresponding to 21 180 euro/patient in the first, 6500 euro/patient in the second and 682 euro/patient in the third year of treatment, with a significant net benefit in favour of sVLPD even in a worst-case hypothesis. CONCLUSION The initiation of sVLPD in elderly CKD5 subjects is a safe and beneficial strategy for these patients and allows them to gain economic resources that can be allocated to further health care investments.

How to Manage Elderly Patients with Chronic Renal Failure: Conservative Management versus Dialysis

Over the past decade the number of elderly patients reaching end-stage renal disease has more than doubled. A fundamental medical decision that nephrologists commonly have to make is when to start dialytic treatment in elderly patients. Evidence is needed to inform about decision-making for or against dialysis, in particular in those patients frequently affected by multiple comorbidities for which dialysis may not increase survival. In fact, this decision affects quality of life, incurs significant financial costs, and finally mandates use of precious dialysis resources. The negative consequence of initiating dialysis in this group of patients can be deleterious as elderly people are sensitive to lifestyle changes. Furthermore, among dialysis patients, the elderly suffer the highest overall hospitalization and complication rates and most truncated life expectancy on dialysis of any age group. Studies of the factors that affect outcomes in elderly patients on dialysis, or the possibility in postponing in a safe way the start of a dialytic treatment, were lacking until recent years. Recently in the literature, papers have been published that address these questions: the effects of dialysis on morbidity and mortality in elderly patients and the use of a supplemented very low protein diet (sVLPD) in postponing the start of dialysis in elderly. The first study demonstrated that, although dialysis is generally associated with longer survival in patients aged >75 years, those with multiple comorbidities, ischemic heart disease in particular, do not survive longer than those treated conservatively. The second one is a randomized controlled study that compared a sVLPD with dialysis in 112 non-diabetic patients aged >70 years. Survival was not different between the two groups and the number of hospitalizations and days spent in hospital were significantly lower in those on a sVLPD. These studies add to the limited evidence that is currently available to inform elderly patients, their carers and their physicians about the risk and the benefit of dialysis.

Assessment of Nutritional Practice in Italian Chronic Kidney Disease Clinics: A Questionnaire-Based Survey

BACKGROUND The prevention of malnutrition in patients with progressive chronic kidney disease (CKD) presents a challenge to nephrologists. We evaluated nutritional practice and routines, at a national level, related to the nutritional management of nondialyzed CKD patients. METHODS A questionnaire-based survey (32 open and 9 multiple-choice questions) was used to assess the evaluation of nutritional status in nondialyzed CKD outpatients at baseline and during follow-up. Data were obtained for 230 Italian public nephrology centers (63% of the total number of Italian public nephrology centers). RESULTS There was a dedicated dietitian at only 19% of the centers. At baseline, body weight, body mass index, and serum albumin were determined in almost all centers, nutrient intakes and bioimpedance analysis in half the centers, and subjective global assessment and skinfold thickness in a small proportion of centers. During follow-up, the rate of assessments decreased by 8% for weight, 14% for nutrient intake, and 29% for subjective global assessment and skinfold thickness. Overall, the K/DOQI minimum criteria for nutritional assessment were fulfilled in only two thirds and half of the clinics at baseline and during follow-up, respectively. Multivariate analysis showed that the number of nutritional variables evaluated was significantly related to the size of the CKD clinic and the presence of a dietitian at baseline, but only with the presence of dietitian during follow-up. Daily urinary output was collected at 90% of the centers, but urea and sodium excretions were determined in only 59% and 57% of cases, respectively. The rate of assessment for urinary solutes during follow-up was higher at centers where a very low protein diet was prescribed. CONCLUSIONS The indications about nutritional assessment for CKD patients are poorly translated into practice patterns, especially with respect to the evaluation of nutrient intakes and additional but simple variables such as skinfold-thickness measurement and bioimpedance analysis. The presence of a dedicated dietitian appears to improve the quality of nutritional assessment in CKD.

Effect of Oral Sodium Bicarbonate Supplementation on Interdialytic Weight Gain, Plasma Sodium Concentrations and Predialysis Blood Pressure in Hemodialysis Patients

Background: Correction of metabolic acidosis in dialysis patients should be considered of paramount importance. However, consuming sodium bicarbonate tablets during the interdialytic interval to reach predialysis bicarbonate levels of 23–24 mmol/l is not widespread due to the fear of greater interdialytic weight gain and fluid overload. For this reason we investigated in a cross-sectional and in an interventional study the effect of oral sodium bicarbonate supplementation on body weight gain, plasma sodium concentrations and predialysis blood pressure in a group of stable uremic patients on regular hemodialysis (HD) treatment. Study Design: 110 patients (67 men, 43 women), mean age 67 ± 15 (range 22–89) years, on regular chronic HD treatment for 6–372 (median 48) months were studied. 70 patients were on regular oral bicarbonate supplementation for at least 4 weeks (group A), 40 patients were not on oral bicarbonate supplementation (group B). The following parameters were recorded: dry body weight (DBW), interdialytic weight gain (IWG), body mass index (BMI), plasma sodium (Na), serum pH, serum bicarbonate (sBic), Kt/V, normalized protein catabolic rate (PCRn), predialysis systolic (SBP) and diastolic (DBP) blood pressure, and bicarbonate therapy (g/day). 18 patients not on oral bicarbonate supplementation with sBic levels ≤20 mmol/l were started on oral bicarbonate therapy and were prospectively followed in the context of an interventional study of correction of chronic metabolic acidosis. The same parameters were recorded before (pre) and after (post) 4 months of oral bicarbonate supplementation. Results:Serum pH and sBic concentrations were significantly higher in patients in group A compared to patients in group B (pH 7.37 ± 0.02 group A vs. 7.33 ± 0.02 group B: p <0.001: sBic 23.8 ± 1.4 group A vs. 20.9 ± 1.4 group B: p < 0.0001). Age, DBW, BMI, IWG, SBP, DBP, Na, Kt/V and PCRn did not differ between groups. The mean daily dose of oral sodium bicarbonate administered to patients in group A was 1.9 ± 0.9 (range 1–5, median 2) g/day. Also in the 18 patients who started bicarbonate treatment, a significant increase in serum pH and sBic concentrations and a significant reduction in PCRn were observed. No significant change in DBW, IWG, SBP, DBP and Na concentrations after 4 months of treatment was found. Conclusions: Our data show that in stable uremic patients on regular HD treatment, oral daily administration of sodium bicarbonate is effective in correcting mild-moderate chronic metabolic acidosis, and does not cause increased interdialytic body weight gain, different plasma sodium concentrations and different systolic-diastolic blood pressure levels compared to patients not on oral sodium bicarbonate supplementation.

A Delphi consensus panel on nutritional therapy in chronic kidney disease.

The conservative management of chronic kidney disease (CKD) includes nutritional therapy (NT) with the aim to reduce the intake of proteins, phosphorus, organic acids, sodium, and potassium, while ensuring adequate caloric intake. While there is evidence that NT may help to prevent and control metabolic alterations in CKD, the criteria for implementing a low-protein regimen in CKD are still debated. There is no final consensus on the composition of the diet, nor indications for specific patient settings or different stages of CKD. Also when and how to start dietary manipulation of different nutrients in CKD is not well defined. A group of Italian nephrologists participated, under the auspices of the Italian Society of Nephrology, in a Delphi exercise to explore the consensus on some open questions regarding the nutritional treatment in CKD in Italy, generating a consensus opinion for 23 statements on: (1) general principles of NT; (2) indications for and initiation of NT; (3) role of protein-free products; (4) NT safety; (5) integrated management of NT. This Delphi exercise shows that there is broad consensus regarding NT in CKD across a wide range of management areas. These clinician-led consensus statements provide a framework for appropriate guidance on NT in patients with CKD, and are intended as a guide in decision-making whenever possible.

Survival and time-to-transplantation of peritoneal dialysis versus hemodialysis for end-stage renal disease patients: competing-risks regression model in a single Italian center experience

AimsDespite several studies reporting similar outcomes for peritoneal dialysis (PD) and hemodialysis (HD), the former is underused worldwide, with a PD prevalence of 15% in Italy. In 2008, the Unit of Nephrology and Dialysis of the Healthcare Trust of the Autonomous Province of Trento implemented a successful PD program which has increased the proportion of PD incident patients from 7 to 47%. We aimed to assess the effect of this extensive use of PD by comparing HD and PD in terms of survival and time-to-transplantation.MethodsA total of 334 HD and 153 PD incident patients were enrolled between January 2008 and December 2014. After screening for exclusion criteria and propensity score matching, 279 HD and 132 PD patients were analyzed. Survival and time-to-transplantation were assessed by competing-risks regression models, using death and transplantation as primary and competing events.ResultsCrude and adjusted regression models for survival revealed the absence of significant differences between HD and PD cumulative incidence functions (subhazard ratio: 1.09, p = 0.62 and 1.34, p = 0.10, respectively). Differently, crude and adjusted regression models for transplantation revealed a lower time-to-transplantation for PD versus HD patients (subhazard ratio: 2.34, p < 0.01, and 2.57, p < 0.01, respectively). The waiting time for placement in the transplant waiting list was longer in HD than PD patients (330 vs. 224 days, p < 0.01).ConclusionsThe extensive use of PD did not lead to any statistically significant difference in mortality. Furthermore, PD was associated with lower time to transplantation. PD may be a viable option for large-scale dialytic treatment in the advanced chronic kidney disease population.