Sustained post-rituximab B-cell depletion is common in ANCA-associated vasculitis and is affected by sex and renal function.

OBJECTIVE: Despite the increasing use of rituximab in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), it remains unclear what the optimal dosing is, especially for maintenance of remission. A deeper understanding of post-rituximab B-cell repopulation patterns may aid better-tailored treatment. METHODS: This is a monocentric, retrospective study including ANCA-positive AAV patients receiving a single course of rituximab induction. CD19+ B cells were longitudinally monitored with flow cytometry. B-cell repopulation was defined as CD19+ >10 cells/µL. RESULTS: Seventy-one patients were included, the majority with microscopic polyangiitis (75%), myeloperoxidase-ANCA positivity (75%) and with renal involvement (79%). During a median follow-up of 54 months since the first rituximab infusion, 44 patients (62%) repopulated B cells, with a median time to repopulation of 39 months (range 7-102). Patients experiencing B-cell depletion lasting longer than the overall median time to repopulation (39 months) exhibited a lower risk of flare and higher risk of serious infection. In multivariate Cox regression, higher estimated glomerular filtration rate (eGFR) [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.13-2.98 per 30 mL/min/1.73 m2 eGFR] and female sex (HR 2.70, 95% CI 1.37-5.31) were independent predictors of increased rate of B-cell repopulation. CONCLUSION: A subset of AAV patients develop sustained post-rituximab B-cell depletion, which associates with reduced risk of flare and increased risk of serious infection in the long term. Preserved renal function and female sex are associated with faster B-cell repopulation. These observations further highlight the need to personalize immunosuppression to improve clinical outcomes.

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.

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.

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 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.

Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: a prospective randomized multicenter controlled study.

BACKGROUND: A supplemented very-low-protein diet (sVLPD) seems to be safe when postponing dialysis therapy. STUDY DESIGN: Prospective multicenter randomized controlled study designed to assess the noninferiority of diet versus dialysis in 1-year mortality assessed by using intention-to-treat and per-protocol analysis. SETTING & PARTICIPANTS: Italian uremic patients without diabetes older than 70 years with glomerular filtration rate of 5 to 7 mL/min (0.08 to 0.12 mL/s). INTERVENTION: Randomization to an sVLPD (diet group) or dialysis. The sVLPD is a vegan diet (35 kcal; proteins, 0.3 g/kg body weight daily) supplemented with keto-analogues, amino acids, and vitamins. Patients following an sVLPD started dialysis therapy in the case of malnutrition, intractable fluid overload, hyperkalemia, or appearance of uremic symptoms. OUTCOMES & MEASUREMENTS: Mortality, hospitalization, and metabolic markers. RESULTS: 56 patients were randomly assigned to each group, median follow-up was 26.5 months (interquartile range, 40), and patients in the diet group spent a median of 10.7 months (interquartile range, 11) following an sVLPD. Forty patients in the diet group started dialysis treatment because of either fluid overload or hyperkalemia. There were 31 deaths (55%) in the dialysis group and 28 deaths (50%) in the diet group. One-year observed survival rates at intention to treat were 83.7% (95% confidence interval [CI], 74.5 to 94.0) in the dialysis group versus 87.3% (95% CI, 78.9 to 96.5) in the diet group (log-rank test for noninferiority, P < 0.001; for superiority, P = 0.6): the difference in survival was -3.6% (95% CI, -17 to +10; P = 0.002). The hazard ratio for hospitalization was 1.50 for the dialysis group (95% CI, 1.11 to 2.01; P < 0.01). LIMITATIONS: The unblinded nature of the study, exclusion of patients with diabetes, and incomplete enrollment. CONCLUSION: An sVLPD was effective and safe when postponing dialysis treatment in elderly patients without diabetes.

Incremental peritoneal dialysis: a 10 year single-centre experience.

INTRODUCTION: Incremental dialysis consists in prescribing a dialysis dose aimed towards maintaining total solute clearance (renal + dialysis) near the targets set by guidelines. Incremental peritoneal dialysis (incrPD) is defined as one or two dwell-times per day on CAPD, whereas standard peritoneal dialysis (stPD) consists in three-four dwell-times per day. PATIENTS AND METHODS: Single-centre cohort study. Enrollement period: January 2002-December 2007; end of follow up (FU): December 2012. INCLUSION CRITERIA: incident patients with FU ≥6 months, initial residual renal function (RRF) 3-10 ml/min/1.73 sqm BSA, renal indication for PD. RESULTS: Median incrPD duration was 17 months (I-III Q: 10; 30). There were no statistically significant differences between 29 patients on incrPD and 76 on stPD regarding: clinical, demographic and anthropometric characteristics at the beginning of treatment, adequacy indices, peritonitis-free survival (peritonitis incidence: 1/135 months-patients in incrPD vs. 1/52 months-patients in stPD) and patient survival. During the first 6 months, RRF remained stable in incrPD (6.20 ± 2.02 vs. 6.08 ± 1.47 ml/min/1.73 sqm BSA; p = 0.792) whereas it decreased in stPD (4.48 ± 2.12 vs. 5.61 ± 1.49; p < 0.001). Patient survival was affected negatively by ischemic cardiopathy (HR: 4.269; p < 0.001), peripheral and cerebral vascular disease (H2.842; p = 0.006) and cirrhosis (2.982; p = 0.032) and positively by urine output (0.392; p = 0.034). Hospitalization rates were significantly lower in incrPD (p = 0.021). Eight of 29 incrPD patients were transplanted before reaching full dose treatment. CONCLUSIONS: IncrPD is a safe modality to start PD; compared to stPD, it shows similar survival rates, significantly less hospitalization, a trend towards lower peritonitis incidence and slower reduction of renal function.

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

Vascular access in older patients: an Italian survey.

BACKGROUND: The number of older patients starting hemodialysis is continuously increasing. The type of vascular access plays an important role in dialysis treatment, but it can be difficult to create in older patients. METHODS: This study compared vascular access survival rates and patient survival rates in older (≥65 years) and younger (<65 years) patients starting hemodialysis in 2 Italian hospitals in 2006-2008. RESULTS: The study enrolled 336 patients: 208 ≥65 years and 128 <65 years of age. The vascular accesses used, in order of frequency, were 102 distal arteriovenous fistulas (dAVFs) (49%), 55 midarm AVFs (pAVFs) (26%), 9 arteriovenous grafts (AVGs) (4%) and 42 central venous catheters (CVCs) (20%) in the older patients, and 89 dAVFs (69%), 25 pAVFs (19%), 6 AVGs (5%) and 8 CVCs (6%) in the younger patients. Survival rates of fistula and catheter did not differ between the 2 groups. AVGs failed earlier (p = 0.02) in the older patients. On Cox analysis, age (hazard ratio [HR] = 1.073; p<0.001) and CVC (HR = 4.152; p<0.001) increased the risk of death. CONCLUSION: A fistula is the gold standard for hemodialysis vascular access in older patients if judged appropriately.

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.

Steroid-free immunosuppression regime reduces both long-term cardiovascular morbidity and patient mortality in renal transplant recipients.

The aim of this retrospective study was to assess the impact of steroid therapy on cardiovascular disease (CVD) and patient mortality, in 486 on-CsA renal transplant recipients, with a follow-up of 9.5 +/- 4.3 yr. Two hundred and one patients had their steroids permanently withdrawn at sixth month after transplantation (G1); 285 patients did not (G2) as they were unable (acute rejection after suspension) or unsuitable (because of clinical criteria or immunosuppressive protocols). The CVD considered were coronary artery disease diagnosed by angiography and myocardial infarction. G1 and G2 patients were well-matched regarding CVD risk factors, except for age (G1: 44 +/- 14 yr; G2: 40 +/- 12 yr; p < 0.003), incidence of male (G1: 62%; G2: 72%, p < 0.02) incidence of acute rejection (G1: 39%; G2: 83%, p < 0.0001). Both CVD and deaths occurring during the first year of transplantation were excluded from the analysis. At 20 yr, the cumulative probability of developing a CVD, was 3.8% in G1; 23.8% in G2 (p < 0.0005). Patient survival rate was 95% in G1; 62% in G2 (p < 0.003). Mortality caused by CVD was higher in G2 (4.2% vs. 0.5%; p < 0.03). The Cox analysis identified in steroid therapy the main independent risk factors for both CVD (hazard ratio 9.56 p < 0.0001) and patient mortality (hazard ratio 5.99, p < 0.0001). At 10th and 15th year after transplantation, the mean-daily dose of steroids was 4.2 mg. In the long-term, steroid therapy, even in low-doses, increases significantly both the rate of CVD and patient mortality. This retrospective study suggests that steroid-free regime should always be recommended for the prevention of post-transplant CVD. This relevant statement should be followed by a long-term prospective study.

Predictors of renal and patient outcomes in atheroembolic renal disease: a prospective study.

Atheroembolic renal disease (AERD) is part of a multisystemic disease accompanied by high cardiovascular comorbidity and mortality. Interrelationships between traditional risk factors for atherosclerosis, vascular comorbidities, precipitating factors, and markers of clinical severity of the disease in determining outcome remain poorly understood. Patients with AERD presenting to a single center between 1996 and 2002 were followed-up with prospective collection of clinical and biochemical data. The major outcomes included end-stage renal disease (ESRD) and death. Ninety-five patients were identified (81 male). AERD was iatrogenic in 87%. Mean age was 71.4 yr. Twenty-three patients (24%) developed ESRD; 36 patients (37.9%) died. Cox regression analysis showed that significant independent predictors of ESRD were long-standing hypertension (hazard ratio [HR] = 1.1; P < 0.001) and preexisting chronic renal impairment (HR = 2.12; P = 0.02); use of statins was independently associated with decreased risk of ESRD (HR = 0.02; P = 0.003). Age (HR = 1.09; P = 0.009), diabetes (HR = 2.55; P = 0.034), and ESRD (HR = 2.21; P = 0.029) were independent risk factors for patient mortality; male gender was independently associated with decreased risk of death (HR = 0.27; P = 0.007). Cardiovascular comorbidities, precipitating factors, and clinical severity of AERD had no prognostic impact on renal and patient survival. It is concluded that AERD has a strong clinical impact on patient and renal survival. The study clearly shows the importance of preexisting chronic renal impairment in determining both renal and patient outcome, this latter being mediated by the development of ESRD. The protective effect of statins on the development of ESRD should be evaluated in a prospective study.