A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection.

The SARS-CoV-2 epidemic is pressuring healthcare systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience of four dialysis centers of the Brescia Renal COVID Task Force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (15%). At disease diagnosis, 37 of the 94 (39%) patients (group 1) were managed on an outpatient basis, whereas the remaining 57 (61%) (group 2) required hospitalization. Choices regarding management strategy were made based on disease severity. In group 1, 41% received antivirals and 76% hydroxychloroquine. Eight percent died and 5% developed acute respiratory distress syndrome (ARDS). In group 2, 79% received antivirals and 77% hydroxychloroquine. Forty two percent died and 79% developed ARDS. Overall mortality rate for the entire cohort was 29%. History of ischemic cardiac disease, fever, older age (over age 70), and dyspnea at presentation were associated with the risk of developing ARDS, whereas fever, cough and a C-reactive protein higher than 50 mg/l at disease presentation were associated with the risk of death. Thus, in our population of hemodialysis patients with SARS-CoV-2 infection, we documented a wide range of disease severity. The risk of ARDS and death is significant for patients requiring hospital admission at disease diagnosis.

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.

Vitamin D in patients with chronic kidney disease: a position statement of the Working Group "Trace Elements and Mineral Metabolism" of the Italian Society of Nephrology.

In the late 1970s, calcitriol was introduced into clinical practice for the management of secondary renal hyperparathyroidism in chronic kidney disease (CKD). Since then, the use of calcifediol or other native forms of vitamin D was largely ignored until the publication of the 2009 Kidney Disease Improving Global Outcomes (KDIGO) recommendations. The guidelines suggested that measurement of circulating levels of 25(OH)D (calcifediol) and its supplementation were to be performed on the same basis as for the general population. This indication was based on the fact that the precursors of active vitamin D had provided to CKD patients considerable benefits in survival, mainly due to their pleiotropic effects on the cardiovascular system. However, despite the long-term use of various classes of vitamin D in CKD, a clear definition is still lacking concerning the most appropriate time for initiation of therapy, the best compound to prescribe (active metabolites or analogs), the proper dosage, and the most suitable duration of therapy. The aim of this position statement is to provide and critically appraise the current plentiful evidence on vitamin D in different clinical settings related to CKD, particularly focusing on outcomes, monitoring and treatment-associated risks. However, it should be taken in account that position statements are meant to provide guidance; therefore, they are not to be considered prescriptive for all patients and, importantly, they cannot replace the judgment of clinicians.

Impact of European medicines agency recommendations for hypersensitivity reactions on intravenous iron prescription in haemodialysis centres of the Lombardy region.

BACKGROUND: The European Medicines Agency (EMA) has recommended measures to minimize the risk of hypersensitivity reactions (HSRs) to intravenous iron (IVFe). We analysed the effects of these recommendations on IVFe clinical management among haemodialysis centres (HDCs) in Lombardy, Italy. MATERIALS AND METHODS: A questionnaire was sent to all 117 HDCs to collect information on centre characteristics, e.g. HDC type [hospital centre (HC) vs. centre with limited assistance (CAL)], presence/absence of intensive care unit (ICU) and/or emergency trained staff, IVFe therapy regarding molecules, administration modalities, side effects, and percentage variations in iron prescription between 2014 and 2013 (outcome, Δ-IVFe%). A linear regression model was applied to evaluate the focus effect (ß) of HDC type on the outcome, controlling for possible confounding effects of the other characteristics. RESULTS: Response rate was 73.5 %. IVFe therapy was used in 69.1 % (HDC range 11-100) of patients. Following EMA recommendations, prescription was reduced by 12.6 %, with the largest reduction observed in CALs. No severe HSRs were reported. HCs had more frequently an ICU [97.2 vs. 20 %, odds ratio (OR) = 63.6 (95 % confidence interval 15.56; 537.47), p < 0.001], emergency trained staff [97.2 vs. 61.2 %, OR = 10.7 (2.68; 85.33), p < 0.001] and instrumental facilities (91.7 vs. 58 %, OR = 5.8 (2.03; 23.55), p < 0.001] than CALs. Linear regression demonstrated a significant raw effect of HDC type on Δ- IVFe% [ß =  19.6 (9.82; 30.63), p < 0.001]. No association was found when HDC type was adjusted for ICU-presence [ß = 6.7 (-2.32; 18.30), p = 0.199] or for all-confounding factors [ß = 5.6 (-5.50; 17.08), p = 0.337]. CONCLUSIONS: This survey shows a disparity in IVFe therapy prescription following EMA recommendations, which is largely influenced by the presence/absence of ICUs in HD centres.

Total Convection Affects Serum ß2 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 ß2 microglobulin (Δß2M), 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. 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), ß2M: 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 Δß2M (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 Δß2M, 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, ß2M, and ESAdose were observed over time. CONCLUSIONS: Ol-HDF induces a long-term significant reduction in pre-dialysis ß2M 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.

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.

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.

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.

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.

Correction of metabolic acidosis on serum albumin and protein catabolism in hemodialysis patients.

BACKGROUND: The effect of the correction of metabolic acidosis (MA) on serum albumin concentrations (sAlbs) in hemodialysis (HD) patients is controversial. This study evaluated the role of the correction of MA on sAlb concentrations, normalized protein catabolic rate (nPCR), and the effect of the concomitant inflammatory status, in a group of acidotic HD patients. METHODS: The correction of MA by oral supplementation with sodium bicarbonate, and the evaluation of its effect on sAlb, nPCR, and high-sensitivity C-reactive protein (hsCRP), were performed in 29 patients on bicarbonate dialysis for a median of 30 months. Other variables included pre-HD arterial pH, serum bicarbonate, serum creatinine, serum Na, body weight, interdialytic weight gain, pre-HD systolic and diastolic blood pressure, and Kt/V. RESULTS: Serum bicarbonate and pH increased significantly (P < .0001), from 19.1 +/- 0.7 mmol/L to 24.6 +/- 1.1 mmol/L and from 7.33 +/- 0.03 to 7.39 +/- 0.02, respectively (all values with +/- are SD). The nPCR decreased from 1.13 +/- 0.14 g/kg/day to 1.05 +/- 0.14 g/kg/day (P < .0001). The other variables did not change significantly. In 17 patients with high-sensitivity C-reactive protein <10 mg/L, sAlb increased from 3.7 +/- 0.3 g/dL to 4.0 +/- 0.3 g/dL (P < .01), whereas in 12 with high-sensitivity C-reactive protein >or=10 mg/L, sAlb did not change (3.5 +/- 0.17 g/dL vs. 3.4 +/- 0.13 g/dL; P = NS). CONCLUSIONS: Oral sodium bicarbonate supplementation is effective in correcting MA in HD patients and does not affect interdialytic weight gain, plasma Na, and blood pressure. The correction of MA is effective in reducing protein catabolism (nPCR) in both inflamed and less inflamed HD patients, but increases sAlb only in patients without inflammation. In inflamed patients, the correction of MA is not sufficient per se to improve sAlb concentrations.

Association between high ultrafiltration rates and mortality in uraemic patients on regular haemodialysis. A 5-year prospective observational multicentre study.

BACKGROUND: High ultrafiltration rate on haemodialysis (HD) stresses the cardiovascular system and could have a negative effect on survival. METHODS: The effect of ultrafiltration rate (UFR; ml/h/kg BW) on mortality was prospectively evaluated in a cohort of 287 prevalent uraemic patients in regular HD from 1 January 2000 to 31 December 2005. PATIENTS: 165 men and 122 women, age 66 +/- 13 years, on regular HD for at least 6 months, median: 48 months (range 6-372 months). Mean UFR was 12.7 +/- 3.5 ml/h/kg BW, Kt/V: 1.27 +/- 0.13, body weight (BW): 62 +/- 13 kg, PCRn: 1.11 +/- 0.20 g/kg/day, duration of dialysis: median 240 min (range 180-300 min), mean arterial blood pressure (MAP) 99 +/- 9 mm/Hg. One hundred and forty nine patients (52%) died, mainly for cardiovascular reasons (69%). Multivariate Cox regression analysis was utilized to evaluate the effect on mortality of UFR, age, sex, dialytic vintage, cardiovascular disease (CVD), diabetes, dialysis modality, duration of HD, BW, interdialytic weight gain (IWG), body mass index (BMI), MAP, pulse pressure (PP), Kt/V, PCRn. RESULTS: Age (HR 1.06; CI 1.04-1.08; P < 0.0001), PCRn (HR 0.17, CI 0.07-0.43; P < 0.0001), diabetes (HR 1.81, CI 1.24-2.47; P = 0.007), CVD (HR 1.86; CI 1.32-2.62; P = 0.007) and UFR (HR 1.22; CI 1.16-1.28; P < 0.0001) were identified as factors independently correlated to survival. We estimated the discrimination potential of UFR, evaluated at baseline, in predicting death at 5 years, calculating the relative receiver operating characteristic (ROC) curves and the cut-off that minimizes the absolute difference between sensitivity and specificity. CONCLUSIONS: High UFRs are independently associated with increased mortality risk in HD patients. Better survival was observed with UFR < 12.37 ml/h/kg BW. For patients with higher UFRs, longer or more frequent dialysis sessions should be considered in order to prevent the deleterious consequences of excessive UFR.

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 x 1,000/microl, 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 high calcium-phosphate product is associated with high C-reactive protein concentrations in hemodialysis patients.

BACKGROUND: An elevated CaxPO4 product and C-reactive protein (CRP) have been associated with coronary artery calcification and increased cardiovascular mortality in hemodialysis (HD) patients. However, it has not been defined, so far, whether and how both parameters are related to each other. For this reason we have evaluated in a cross-sectional and in an interventional study the possible correlation between CaxPO4 and CRP and the effect of the correction of a high CaxPO4 on CRP levels. METHODS: 47 uremic patients (age 65 +/- 16 years) on regular chronic HD were selected from a total population of 125 prevalent patients treated at our Institution. Patients had no clinical evidence of either acute infectious or inflammatory diseases for at least 4 weeks before the study. They were on regular bicarbonate HD for 6-329 months (median 42). CRP, hemoglobin (Hb), serum albumin (sAlb), protein catabolic rate (PCRn), serum calcium (Ca), serum phosphorus (PO4), CaxPO4, intact PTH, Kt/V, presence of ischemic heart disease (IHD) and/or peripheral vascular disease (PVD) were recorded. CRP was Ln-transformed in all statistical analyses because of positive skewness. RESULTS: The main findings were: LnCRP 2.17 +/- 0.77 mg/l, Ca 10.1 +/- 0.4 mg/dl, PO4 5.8 +/- 0.6 mg/dl, CaxPO4 59 +/- 6 mg2/dl2, andPTHint 218 +/- 195 ng/ml. 18/47 had IHD, 18/47 PVD. A significant hyperbolic correlation between CaxPO4 and CRP was observed. A piecewise linear regression model analysis identified a break-point for CaxPO4 at 55 mg2/dl2. Comparison of CRP levels after the division of the patients into two groups according to CaxPO4 break-point (group A, CaxPO4 < or = 55 mg2/dl2, n = 16 patients; group B, CaxPO4 >55 mg2/dl2, n = 31 patients) showed that CRP levels were significantly lower in patients in group A (LnCRP 1.43 +/- 0.22 mg/l) than in group B (LnCRP 2.55 +/- 0.67 mg/l, p < 0.0001). Multiple regression analysis bearing LnCRP as dependent variable confirmed CaxPO4 as the most significant variable among the other variables examined. In 22 patients with CaxPO4 > or = 60 mg2/dl2, we performed intensive lowering of the CaxPO4 product in order to reach and maintain a CaxPO4 , or =55 mg2/dl2 for 3 months. At the end of observation, a significant reduction in CaxPO4 and LnCRP was observed (CaxPO4 pre 62.8 +/- 1.9 vs. post 46.3 +/- 6.2 mg2/dl2: p < 0.0001; LnCRP pre 2.32 +/-0.36 vs. post 1.83 +/- 0.14 mg/l: p < 0.0001). No significant variation in the other biochemical parameters was observed. CONCLUSIONS: Our data show that in chronic HD patients in steady clinical conditions with no clinical evidence of either infectious or inflammatory diseases, a high CaxPO4 is associated with high CRP concentrations. Intensive lowering of CaxPO4 reduces CRP

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), K(t)/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

Inter-dialytic variations in blood volume and total body water in uraemic patients treated by dialysis.

BACKGROUND: An optimal balance of sodium and water is one of the most important goals of haemodialysis (HD) therapy. However, while inter-dialytic variations in blood volume (BV) have been well described, very little is known about the dynamics of fluid accumulation and distribution in body compartments during the inter-dialysis period. METHODS: We studied inter-dialysis variations in BV, measured as percent variation of plasma haemoglobin (Hb) concentrations (% triangle up BV) and percent variation of total body water (% triangle up TBW), in 24 uraemic patients treated by standard bicarbonate dialysis. These parameters were determined at the end of the last weekly dialysis (T0), after 24 h (T1), 48 h (T2), and at the beginning of the following dialysis session (T3). At each time point we measured Hb, haematocrit (Hct), serum albumin (sAlb), plasma sodium (Na), plasma potassium (K), blood urea nitrogen (BUN), plasma osmolality (Osm), body weight (BW), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). All patients were clinically stable and had no evidence of acute blood loss in the 3 weeks before the study. RESULTS: During the inter-dialysis period, there were increases in BUN, K and Osm, but Na did not change. SBP and DBP also did not change. HR tended to decrease, and showed a significant reduction between T0 and T3. TBW increased in a linear fashion whereas BV increased exponentially, showing a slow rise during the first 24 h followed by a greater increase in the following time intervals. This was confirmed by concomitant but opposite percent variations in Hct and sAlb concentrations. CONCLUSIONS: Despite the limitations of the current methodology, our data show that the increase in TBW is redistributed during the long inter-dialysis period and this may prevent the effects of a too premature expansion of the intra-vascular compartment. This is especially evident during the first 24 h after HD, during which % triangle up BV is lowest, indicating a preferential distribution of the fluid load towards the extra-vascular space. During the following time intervals, the extra-vascular compartment refills in conjunction with an exponential expansion of BV that reaches its maximum in the last 24 h before HD.

Epoetin requirement does not depend on dialysis dose when Kt/N > 1.33 in patients on regular dialysis treatment with cellulosic membranes and adequate iron stores.

BACKGROUND: An inverse correlation between Kt/V and epoetin requirement has recently been demonstrated in stable hemodialysis (HD) patients with adequate iron stores, dialyzed with cellulosic membranes. However, there is no evidence as to whether or not this effect continues for Kt/V even in the adequate or higher range. METHODS: We investigated the relationship between Kt/V and the weekly epoetin dose in 85 stable HD patients (age 63 +/- 16 years) treated with bicarbonate HD and unsubstituted cellulose membranes for 6-338 months (median: 70 months). INCLUSION CRITERIA: HD for at least 6 months, subcutaneous rHuEPO for at least 4 months, transferrin saturation (TSAT) > or = 20%, serum ferritin > or = 100 ng/mL, hemoglobin (Hb) level targeted to approximately equal to 12 g/dL for at least 3 months. EXCLUSION CRITERIA: HBsAg and HIV positivity; need for blood transfusions or evidence of blood loss in the 3 months before the study, acute and chronic infections. To evaluate the effect of dialysis adequacy on the epoetin requirement, we also performed the same analysis after dividing of the patients according to Kt/V. Hematocrit (Hct) and Hb levels were evaluated weekly for 3 weeks; TSAT, serum ferritin, Kt/V, PCRn, serum albumin (sAlb), and weekly epoetin dose were evaluated at the end of observation. No change in dialysis or therapy prescription was made during the study. RESULTS: The results for all the patients were: Hct 36 +/- 2 %, Hb 12 +/- 0.7 g/dL, TSAT 28 +/- 7%, serum ferritin 234 +/- 171 ng/mL, sAlb 4.2 +/- 0.4 g/dL, Kt/V 1.33 +/- 0.17, PCRn 1.15 +/- 0.28 g/Kg/day, weekly epoetin dose 117 +/- 74 U/Kg. There was no correlation between Hb and Kt/V, whereas there was an inverse correlation between the reciprocal of the weekly epoetin dose and Kt/V (r = -0.448, p = 0.0001). Further regression line analysis showed a break-point for Kt/V at the level of 1.33. In the 52 patients with Kt/V < 1.33, the correlation was confirmed between epoetin and Kt/V (r = - 0.563, p = 0.0001), while in the 33 patients with Kt/V > or = 1.33, there was no correlation between epoetin dose and Kt/V (r = 0.021, p = NS). In these patients, multiple regression analysis, with the weekly epoetin dose as a dependent variable, confirmed Kt/V as a non-significant factor. CONCLUSIONS: In iron-replete HD patients on cellulosic membranes and stabilized epoetin therapy, inadequate dialysis was associated with higher epoetin requirement, but for Kt/V values > or = 1.33, there was no further effect on epoetin responsiveness.

Predialysis versus postdialysis hematocrit evaluation during erythropoietin therapy.

American guidelines for the management of renal anemia by recombinant human erythropoietin (rHuEPO) recommend collecting a predialysis blood sample to evaluate hemoglobin (Hb) and hematocrit (Hct) levels in hemodialysis patients. Although a predialysis blood sample is appropriate for evaluating when to start rHuEPO treatment, the same sample would not be appropriate for evaluating the target Hb/Hct to be maintained, particularly when normal or near-normal values are pursued. We measured the degree of intradialytic and extradialytic variation of Hb, Hct, and body weight in 68 stable hemodialysis patients on maintenance subcutaneous rHuEPO treatment. Hb and Hct concentrations were determined before and after dialysis. In 16 patients, Hb and Hct concentrations also were assessed 24 hours after the end of dialysis. Predialysis versus postdialysis Hb and Hct concentrations for all patients were 10.5 +/- 1.3 g/dL versus 11.5 +/- 1.3 g/dL (P < 0.0001) and 32 +/- 4% versus 35 +/- 4% (P < 0.0001). The intradialytic percent variation (%Delta) of Hct and body weight were 10 +/- 6% and -6.3 +/- 3.5%. There was a close inverse correlation between %Delta of Hct and Hb and %Delta of body weight (P < 0.0001). In patients with body weight losses 2.5 kg or more per session, the mean %Delta of Hct was 12 +/- 7%. In the 16 patients studied 24 hours after the end of the dialysis session, Hct and Hb values remained significantly higher compared with the predialysis levels (P < 0.001), suggesting a slow reequilibration of the intravascular volume in the first 24 hours after hemodialysis. For these reasons, predialysis samples for monitoring the target Hb and Hct levels in patients treated by rHuEPO should be considered with caution.