Paola Gaggia

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.

A prospective randomized trial on azathioprine addition to cyclosporine versus cyclosporine monotherapy at steroid withdrawal, 6 months after renal transplantation

BACKGROUND Many attempts have been made to withdraw steroid therapy in renal transplant patients in order to avoid its many side effects. Results have been, so far, controversial. In this randomized prospective study, we compare the efficacy of azathioprine adjuncts to cyclosporine at the time of steroid withdrawal, 6 months after transplantation, versus Cyclosporine monotherapy, in preventing acute rejection. METHODS One hundred and sixteen kidney transplant patients with good and stable renal function (creatininemia <2 mg/dl) received, in the first 6 months, cyclosporine + steroid. They were then randomized into two groups (A and B), and steroid therapy was withdrawn over 2 months. Group A (58 patients) continued on cyclosporine monotherapy, whereas group B (58 patients) added azathioprine (1 mg/kg/day) at the beginning of randomization and continued on cyclosporine + azathioprine. In both groups, patients resumed steroid therapy at the first episode of acute rejection. Follow-up after randomization was 5.3+/-1.6 years. RESULTS After 5 years, the incidence of steroid resumption was 57% in group A and 29% in group B (P<0.02); of those, 68% and 88% of them were within 6 months from randomization. Anti-rejection therapy was always successful. Five-year patient and graft survival rates were 90% and 88% in group A and 100% and 91% in group B. Creatininemia did not differ, at follow-up. Side effects differed only for mild and reversible leukopenia caused by azathioprine in group B. CONCLUSION Cyclosporine plus azathioprine is more effective than cyclosporine monotherapy in reducing the incidence of acute rejection after steroid withdrawal. Graft loss as a result of chronic rejection, mild in both groups, did not differ. Steroid withdrawal is feasible and advantageous, and the addition of azathioprine allowed 71% of our selected patients to remain steroid-free.

Effect of post-dilutional on-line haemodiafiltration on serum calcium, phosphate and parathyroid hormone concentrations in uraemic patients

BACKGROUND Strict control of serum calcium and phosphate concentrations is paramount to prevent secondary hyperparathyroidism in haemodialysis (HD) patients. Standard intermittent low-flux HD (Lf-HD) is not sufficient to reach this goal. The aim of this study was to evaluate the effect of on-line haemodiafiltration (Ol-HDF) on serum calcium (sCa), phosphate (sPO4) and parathyroid hormone (PTHint) concentrations. METHODS Of the 220 patients screened, 65 met the inclusion criteria for the study; 30 of whom agreed to participate in the study (Study group), the others were considered as the control group (Controls). Protocol for Study the group consisted of 6 months conventional Lf-HD (Period 1) and 6 months of post-dilutional Ol-HDF (Period 2). Controls continued their usual Lf-HD and were followed for 12 months. The main variables evaluated at the start and at the end of each period were sCa, sPO(4) and PTHint. RESULTS The switchover from Lf-HD to Ol-HDF resulted in a significant reduction of sPO4 (from 5.1 ± 1.0 to 4.0 ± 0.7; P < 0.0001) and PTHint concentrations (from 307 ± 167 to 194 ± 98; P < 0.0001), no significant changes were found in both sCa concentrations (from 9.1 ± 0.7 to 8.9 ± 0.6) and phosphate binder dose. Kt/Vurea increased significantly, and beta(2) microglobulin concentrations decreased significantly. In the Controls, no significant variations of the same variables were observed over time, except for a significant increase in sevelamer intake. CONCLUSION This study supports the idea that Ol-HDF could be better than Lf-HD in controlling mineral metabolism in HD patients.

Magnitude of end-dialysis overweight is associated with all-cause and cardiovascular mortality: a 3-year prospective study.

Background: We hypothesized that the difference between the prescribed end-dialysis body weight, defined end-dialysis over-weight (edOW; kg), and the body weight which is actually attained could impact survival in hemodialysis (HD) patients. The aim of this prospective observational study was to evaluate if edOW could influence survival in a cohort of prevalent HD patients, controlled for multiple dialysis and clinical risk factors and followed for 3 years. Methods: One hundred and eighty-two patients (117 men, age 65 ± 13 years) on regular HD treatment for at least 6 months [median 48 months (range: 6-366)] were followed from January 1, 2008 to December 31, 2010. Eighty-four patients (46%) did not achieve their prescribed dry body weight (dBW); their median edOW was 0.4 kg (range: 0.1-1.4). Ninety-eight died during observation, mainly from cardiovascular reasons (69%). Multivariate Cox regression analysis was utilized to evaluate the effect edOW, ultrafiltration rate (UFR), interdialytic weight gain (IDWG), age, sex, dialytic vintage, cardiovascular disease, antihypertensive therapy, diabetes, duration of HD, dBW, BMI, mean arterial blood pressure, Kt/V, and protein catabolic rate (PCRn) had on mortality. Results: Age (HR: 1.04; CI: 1.03-1.05; p <0.0001), IDWG (HR: 2.62; CI: 2.06-3.34; p < 0.01), UFR (HR: 1.13; CI: 1.09-1.16; p< 0.01), PCRn (HR: 0.02; CI: 0.01-0.04; p <0.001), and edOW (HR: 2.71; CI: 1.95-3.75; p < 0.02) were independently correlated to survival. The relative receiver operating characteristic curve identified a cutoff value of 0.3 kg for edOW in predicting death. Conclusions: High edOW is independently associated with an increased long-term risk of all-cause and cardiovascular mortality in HD patients. Better survival was observed in patients with edOW <0.3 kg. For patients with higher edOW, longer or more frequent dialysis sessions should be considered in order to prevent the deleterious consequences of excessive body fluid expansion.

Role of Dialysis Sodium Gradient on Intradialytic Hypertension: An Observational Study

Introduction: The causes of intradialytic hypertension (IDHyper) are not well understood and this condition can complicate the clinical management of hemodialysis (HD) patients. Aim: To evaluate the potential role of intradialytic sodium gradient (NaG) on blood pressure values and IDHyper during HD. Patients and Methods: 206 prevalent HD patients on 3 times weekly HD treatment for at least 6 months (dialytic vintage 6-240 months) followed at our institution were studied. Mean age was 68 ± 14 years, 129 were men. For 2 consecutive months (24 HD sessions) after the start of observation, the following variables were evaluated in predialysis after the long interdialysis interval: pre-HD plasma sodium (pNa, mmol/l) and potassium (pK, mmol/l) concentrations (mean value of 8 determinations), pre- and post-HD systolic (SBP, mm Hg) and diastolic (DBP, mm Hg) blood pressure, dry body weight (dBW, kg), interdialytic weight gain (IDWG, kg), ultrafiltration rate (UFR, ml/kg/h), dialysis dose (Kt/V), protein catabolic rate (PCRn, g/kg/day), hemoglobin (Hb, g/dl). SBP, DBP, IDWG, UFR are the mean values of the 24 HD sessions. 76% of patients were on antihypertensive therapy, 171 patients were on bicarbonate HD, and 35 on HDF. Dialysate Na concentration was set at 140 mmol/l in all patients. Duration of HD and the blood and dialysate flow rate were kept constant during observation. Statistical Analysis: Data are expressed as mean ± SD; linear and multiple regression analysis and t test for unpaired data were employed. Significant differences were defined as p < 0.05. Results: Pre-HD pNa was 138.1 ± 2.3 mmol/l, pK 5.0 ± 0.4 mmol/l, dBW 67 ± 14 kg, IDWG 2.9 ± 0.8 kg, UFR 11.2 ± 3.7 ml/kg/h, Kt/V 1.43 ± 0.18, PCRn 1.13 ± 0.17 g/kg/day, and Hb 11.2 ± 0.8 g/dl. Pre- and post-HD SBP values were 139 ± 13 and 134 ± 12 mm Hg (p < 0.0001); pre- and post-HD DBP did not change significantly. A dialysis Na gradient (NaG) (dialysate Na - pre-HD pNa) was calculated, as well as the delta of SBP (ΔSBP) (post-HD SBP - pre-HD SBP). IDHyper was defined as ΔSBP >0. A significant direct correlation was found between NaG and ΔSBP (p < 0.0001) and multiple regression analysis with ΔSBP as dependent variable confirmed the strong correlation with NaG (p < 0.00001). According to ΔSBP behavior, 171 patients (83%) had a decrease or no change in post-HD SBP (group 1; no IDHyper); 35 patients (17%) increased their post-HD SBP (group 2; IDHyper). NaG values were significantly greater in patients in group 2 (group 1: 1.5 ± 2.2 vs. group 2: 3.3 ± 2.5, p < 0.0001). Conclusions: This study shows that the intradialytic ΔSBP is independently and strongly associated with the dialytic NaG. The more positive the NaG (net intradialytic Na gain), the more positive the ΔSBP and IDHyper.

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.

Total Convection Affects Serum β2 Microglobulin and C-Reactive Protein but Not Erythropoietin Requirement following Post-Dilutional Hemodiafiltration

Background: Inflammation and increased erythropoiesis stimulating agents (ESA) requirement are frequently associated in patients on dialysis. On-line hemodiafiltration (ol-HDF), putting together high levels of diffusion, and convection could improve both conditions. However, it is still not known which depurative component plays a major role in determining this result. The aim of the study was to evaluate the role of convection and diffusion on long-term variations of serum β2 microglobulin (Δβ2M), high-sensitive C-reactive protein (ΔhsCRP) concentrations, and ESA requirement (ΔESA) in ol-HDF. Methods: Seventy-three patients prevalent on high flux HD (hfHD) were studied. Thirty-eight patients were switched from hfHD to post-dilutional ol-HDF (Study group); the other 35 patients were considered the Control group. At 6 and 12 months, the effects of ol-HDF and hfHD on ΔhsCRP, ΔB2M, and ΔESA (U/kg/week) were evaluated. Other variables considered were body weight (BW), serum albumin (sAlb), hemoglobin (Hb), and equilibrated Kt/V (eKt/V). Iron therapy and ESA were administered intravenously according to the K/DOQI guidelines in order to maintain transferrin saturation between 20 and 40%, serum ferritin between 150 and 500 ng/ml and Hb between 11 and 12 g/dl. Qb, treatment time and Qd remained constant. Ol-HDF and hfHD were performed using membranes of size 1.9-2.1 sqm. Ultrapure dialysate and substitution fluid were employed in both HDF and HD treatments. Data are expressed as mean ± SD. Paired t test, Mann-Whitney U test, and simple and multiple regression analyses were employed for statistical evaluation. Results: Study group: total convective volume (TCV) was 22.1 ± 1.9 l/session. A significant reduction of hsCRP: from 6.8 ± 7.1 to 2.3 ± 2.4 mg/dl (p < 0.001), β2M: from 36.5 ± 14.4 to 24.7 ± 8.6 mg/dl (p < 0.0001) and ESAdose: from 107 ± 67 to 65 ± 44 U/kg/week (p < 0.005) was observed. No significant variations of Hb, BW and sAlb were seen. A significant inverse correlation was found between TCV and Δβ2M (r = -0.627; p < 0.0001), and TCV and ΔhsCRP (r = -0.514; p < 0.0001); no correlation between TCV and ΔESAdose was observed. No correlation was found between eKt/V and Δβ2M, ΔhsCRP, and ΔESAdose. Multiple regression analysis with ΔESAdose as dependent variable showed ΔhsCRP as the only significantly associated independent factor (p < 0.01). Control group: no significant variations of hsCRP, β2M, and ESAdose were observed over time. Conclusions: Ol-HDF induces a long-term significant reduction in pre-dialysis β2M and hsCRP concentrations. The magnitude of reduction is directly correlated to the amount of TCV achieved but not on eKt/V. The observed reduction in ESAdose requirement is independent either on convection or diffusion, but is directly associated to the concomitant reduction of inflammation.

Use of Renin-Angiotensin System Blockers Increases Serum Potassium in Anuric Hemodialysis Patients

Background: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are increasingly used in uremic patients (pts). However, their effect on serum potassium (sK) concentrations in anuric pts on chronic hemodialysis treatment (HD) is controversial. The aim of the study was to evaluate sK before and after the start of ACEi/ARB therapy. Methods: In the period 1/1/2015 – 31/12/2015, 112 out of 240 prevalent HD pts on thrice weekly HD treatment followed at our institution started the ACEi/ARB therapy. The mean age was 67 ± 14 years, 67/112 were men, dialysis vintage was 6–212 months. In the 3 months before (PRE; N° 36 HD sessions) and after (POST; N° 36 HD sessions) the start of ACEi/ARB therapy, the following variables were evaluated in pre dialysis after the long interdialysis interval: sK (mean of 12 determinations; mmol/L), maximum sK (maximum K value observed during observations; sKmax; mmol/L), serum sodium (sNa; mmol/L), pre dialysis systolic blood pressure (SBP; mm Hg) and diastolic blood pressure (DBP; mm Hg), body weight (BW; Kg), interdialytic weight gain (IWG; Kg), Kt/V, serum bicarbonate concentrations (sBic; mmol/L), protein catabolic rate (PCRn; g/KgBW/day). SBP, DBP, IWG are the mean of the 24 HD sessions. Out of 112 patients, 102 were on antihypertensive therapy. The duration of HD and blood and dialysate flow rates were kept constant. Data are expressed as mean ± SD. Student t test for paired and unpaired data for normally distributed variables, Mann-Whitney test for medians, χ2 test for categorical data were employed to compare groups. A significant difference was defined as p < 0.05. Results: sK increased from 5.0 ± 0.4 mmol/L PRE to 5.7 ± 0.5 mmol/L POST (p < 0.0001). sKmax increased from 5.3 ± 0.5 mmol/L PRE to 6.2 ± 0.6 mmol/L POST (p < 0.0001). The percentage of pts with normal sK concentrations decreased from 82% PRE to 29% POST (p < 0.0001). Mild hyperkalemia increased from 18 to 52% (p < 0.001); in 31% of the patients, it was necessary to reduce the K dialysate concentration. None of the patients had severe hyperkalemia PRE, but 19% developed severe hyperkalemia POST (p < 0.0001) necessitating treatment withdrawal. Mean sK in these pts varied from 5.2 ± 0.3 mmol/L PRE to 6.5 ± 0.2 mmol/L at the moment of withdrawal (p < 0.0001) and sKmax from 5.5 ± mmol/L PRE to 6.9 ± 0.3 mmol/L (p< 0.0001). After withdrawal of ACEi/ARB, sK and sKmax concentrations decreased to basal levels within 1 month. There were no significant changes of BW, IWG, SBP, DBP, Na, Hb, Kt/V, sBic, and PCRn in both periods. Conclusions: ACEi/ARB therapy is associated with an increased risk of hyperkalemia in anuric hemodialysis patients. The proportion of patients with normal sK concentrations decreased from 82 to 29% and with mild hyperkalemia increased from 18 to 52%. Severe hyperkalemia necessitating the interruption of ACEi/ARB therapy developed in 19% of patients. This suggests great caution in the widest utilization of this class of drugs in HD patients.