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BACKGROUND AND AIMS A complex interplay lies between COVID-19 infection and kidney disease. Patients with COVID-19 are at an increased risk of acute kidney injury (AKI), while CKD patients represent a population at a high risk of mortality from COVID-19 [1]. For 3 years, our hospital has been running an intradyalitic vaccination project (HBV, Haemophylus, Pneumococcus, Influenza) for haemodialysis patients. No data regarding the anti-COVID-19 vaccination administered during the dialysis session are available yet. This is a safety study aimed at defining the feasibility of this vaccination protocol. METHOD A total of 186 haemodialysis patients from 3 centres were vaccinated with the Spikevax-Moderna vaccine (Fig. 1). According to Italian law, patients with a COVID-19 infection in the previous 12 months received only one dose. The administration was performed between 1 and 2 h after the start of the dialysis session. Data regarding mild adverse events were collected. In 117 patients, a titration of the anti-RBD S1 antibodies of the virus spike antigen was performed 1 month after the completion of the vaccination [2]. Therefore, a new titration was obtained after 3 months in 50 patients. RESULTS Of the 117 patients, 65 (55.5%) were male, with a mean age of 69.2 ± 13.1 years. Of these, 25 patients (21.3%) showed mild adverse events without compromising dialysis administration. No serious adverse events took place. Seroconversion was noticed in 111 patients (94.9%) after 1 month, with a mean anti-RBD S1 antibody titer of 751.1 ± 610.5 BAU/mL. When a new titration was performed after 3 months, the titer decreased to 203.1 ± 134.3 BAU/mL (t-test; P = 0.005). CONCLUSION Intradialytic vaccination is a procedure with an excellent safety profile that may be implemented in dialysis settings. Further studies should be permormed to confirm these results.

Background and Aims It is estimated that Chronic Kidney Disease (CKD) accounts for 5 to 10 million deaths annually, mainly due to cardiovascular (CV) diseases. Although traditional CV risk factors are prevalent, other non-traditional CV risk factors such as vascular calcification (VC) are believed to contribute to this disproportionate CV risk burden in CKD subjects. We sought to investigate the association of Coronary Artery Calcification (CAC) progression with all-cause mortality in a cohort of patients new to hemodialysis (HD). Method This is a post hoc analysis of the Independent study (NCT00710788) originally designed to test the impact of 2 different phosphate binder regimens on various hard as well as surrogate endpoint in HD subjects. A total of 412 (88.4% of the Independent study cohort) underwent repeated CAC quantification according to the Agatston methods at study inception as well as after 12 months of follow-up. The square root method was used to assess CAC progression (CACP) and survival analyses were used to check the association of CACP and all-cause mortality. Results 412 middle age (65 years) men and women (51.2%) were considered. Detectable CAC was present in about 2 out 3 patients (68.2%) at study inception. At 12 months of follow-up completion, about 1 out of 3 subjects (33.1%) experience a significant CACP. CACP was associated with older age and use of calcium-based phosphate binders. At study completion (median follow-up: 36 months) 106 patients expired of all-cause. Age, diabetes mellitus, atherosclerotic CV events, baseline CAC extension were predictors of unfavorable outcome. Multivariable adjusted analysis confirmed an independent association of both baseline CAC (Hazard Ratio 1.29; 95% Confidence Interval: 1.17-1.44) and CACP (HR: 5.16; 95%CI: 2.61-10.21) with all-cause mortality. However, CACP diminished the risk associated with baseline CAC (p for interaction term 0.002) and use of calcium-free phosphate binders significantly weakened the link between CACP (HR. 1.95; 95%CI: 0.92-4.16) and mortality Conclusion Baseline CAC as well as CACP predict mortality in incident to HD individuals. Nevertheless, CACP mitigates the risk associated with baseline CAC and calcium-free phosphate binders attenuates the association of CACP and mortality, suggesting that CACP modulation may impact survival in this population

BACKGROUND Very low-protein intake during chronic kidney disease (CKD) improves metabolic disorders and may delay dialysis start without compromising nutritional status, but concerns have been raised on a possible negative effect on survival during dialysis. This study aimed at evaluating whether a very low-protein diet during CKD is associated with a greater risk of death while on dialysis treatment. METHODS This is an historical, cohort, controlled study, enrolling patients at dialysis start previously treated in a tertiary nephrology clinic with a very low-protein diet supplemented with amino acids and ketoacids (s-VLPD group, n = 184) or without s-VLPD [tertiary nephrology care (TNC) group, n = 334] and unselected patients [control (CON) group, n = 9.092]. The major outcome was survival rate during end-stage renal disease associated to s-VLPD treatment during CKD. The propensity score methods and Cox regression model were used to match groups at the start of dialysis to perform survival analysis and estimate adjusted hazard ratio (HR). RESULTS In s-VLPD, TNC and CON groups, average age was 67.5, 66.0 and 66.3 years, respectively (P = 0.521) and male prevalence was 55, 55 and 62%, respectively (P = 0.004). Diabetes prevalence differed in the three groups (P < 0.001), being 18, 17 and 31% in s-VLPD, CON and TNC, respectively. A different prevalence of cardiovascular (CV) disease was found (P < 0.001), being similar in TNC and CON (31 and 25%) and higher in s-VLPD (41%). Median follow-up during renal replacement therapy (RRT) was 36, 32 and 36 months in the three groups. Adjusted HR estimated on matched propensity patients was 0.59 (0.45-0.78) for s-VLPD versus CON. Subgroup analysis showed a lower mortality risk in s-VLPD versus matched-CON in younger patients (

Whether convective therapies allow better control of serum phosphate (P) is still undefined, and no data are available concerning on-line haemofiltration (HF). The objectives of the study are to evaluate the effect of convective treatments (CTs) on P levels in comparison with low-flux haemodialysis (HD) and to evaluate the correlates of serum phosphate in a post hoc analysis of a randomized clinical trial.This analysis was performed in the database of a multicentre, open label and randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: on-line pre-dilution HF (36 patients) or on-line pre-dilution haemodiafiltration (40 patients).CTs did not affect P (P = 0.526), calcium (Ca) (P = 0.849) and parathyroid hormone levels (P = 0.622). P levels were associated with the use of phosphate binders including aluminium-based phosphate binders (P0.001) and sevelamer (P0.001), pre-dialysis bicarbonate levels (P0.001) and pre-dialysis blood K levels (P0.001). On multivariate analysis (generalized linear model), serum P was again largely unassociated with CTs (P = 0.631). Notably, participating centres were by far the strongest independent correlate of serum P, explaining 45.3% of the variance of serum P over the trial and this association was confirmed at multivariate analysis. Bicarbonate (P0.001) and, to a weaker extent, serum K (P = 0.032) were independently related to serum P.In comparison with low-flux HD, CTs did not significantly affect serum P levels. Participating centres were the main source of P variability during the trial followed by treatment with phosphate binders, serum bicarbonate and, to a weak extent, serum potassium levels (ClinicalTrials.gov Identifier: NCT011583309).

Background. High phosphate levels attenuate nephroprotection through angiotensin-converting enzyme inhibition in patients with proteinuric chronic kidney disease (CKD). Whether this phenomenon holds true for other nephroprotective interventions like very-low-protein diet (VLPD) is unknown. Methods. We tested the hypothesis that phosphate interferes with the anti-proteinuric response to VLPD in a non-randomized, sequential study in 99 proteinuric CKD patients who sequentially underwent low-protein diet (LPD; 0.6 g/kg) and VLPD (0.3 g/kg) supplemented with keto-analogues, each for periods longer than 1 year. Results. Serum phosphate significantly reduced during VLPD (3.2 ± 0.6 mg/dL) when compared with LPD (3.7 ± 0.6 mg/ dL, P < 0.001), an effect paralleled by a substantial decline in phosphate excretion (LPD, 649 ± 180 mg/day; VLPD, 462 ± 97 mg/day; P < 0.001). The median proteinuria during LPD was 1910 mg/24 h (interquartile range: 1445–2376 mg/ 24 h) and reduced to 987 mg/24 h (656–1300 mg/24 h) during VLPD (P < 0.001). No significant change in the estimated glomerular filtration rate (eGFR) was observed during the two diet periods. In linear mixed models including the diagnosis of renal disease, eGFR, 24-h urine sodium and urea and other potential confounders, there was a strong interaction between serum phosphate (P = 0.04) and phosphaturia (P < 0.001) with the anti-proteinuric response to VLPD. Accordingly, 24-h proteinuria reduced modestly in patients who maintained relatively higher serum phosphate levels or relatively higher phosphaturia to be maximal in those who achieved the lowest level of serum and urine phosphate. Conclusion. Phosphate is an important modifier of the antiproteinuric response to VLPD. Reducing phosphate burden may decrease proteinuria and slow the progression of renal disease in CKD patients, an issue that remains to be tested in specific clinical trials.

Background. We investigated the effects of visit-to-visit systolic blood pressure variability (SBPV) on both mortality and dialysis inception in a cohort of chronic kidney disease (CKD) patients not requiring dialysis therapy. Furthermore, we also explored the carry-over effect of visit-to-visit SBPVon mortality after dialysis initiation. Methods. We conducted a longitudinal retrospective, observational, multi-centre study in three tertiary care nephrology outpatient clinics. All the ambulatory CKD patients admitted to the outpatient clinics from 1 January 2004 to 31 December 2005 were screened for study eligibility. We selected all consecutive patients older than 18 years of age with a mean estimated glomerular filtration rate of

Background Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes. Methods Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients). Results CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta2 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta2 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170). Conclusions In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.

Background. Kt/Vurea was established as an index of haemodialysis (HD) adequacy. The use of Vurea as a normalizing factor has been questioned, and alternative parameters such as body weight 0.67 (W 0.67 ), body surface area (BSA), resting energy expenditure (REE), high metabolic rate organ (HMRO) mass, liver size (LV) and more recently, bioelectrical resistance (R), an independent and directly measurable biological parameter, were proposed as alternative methods for scaling dialysis dose. Methods. The present study aimed to prospectively evaluate the predictive power of some demographic, anthropometric, bioelectrical (BIA) and biochemical parameters, of seven scaling parameters, namely Vurea, as derived from the Watson et al. formulae, W 0.67 , BSA, REE, HMRO, LV and R and of eight HD adequacy indices [single-pool variable-volume Kt/Vurea, computed using the Daugirdas equation, its rescaled equivalents (Kt/W 0.67 , Kt/BSA, Kt/ REE, Kt/HMRO, Kt/LV and Kt/R) and Kt] on long-term survival of a cohort of 328 incident white HD patients. All individuals underwent periodical (every 3 months) biochemical evaluations and single-frequency BIA measurements, injecting 800 μA at 50 kHz alternating sinusoidal current with a standard tetrapolar technique. Results. A first Cox regression analysis, testing the predictive power of some demographic, anthropometric, BIA and biochemical parameters, and of the eight HD adequacy indices on long-term survival of the patients, showed that only higher serum creatinine (Scr) levels (P < 0.0001) and lower Kt/R values (P < 0.04) were significant outcome predictors. As Kt was shown not to be an outcome predictor, a second Cox regression analysis, testing the predictive power of the same demographic, anthropometric, BIA and biochemical parameters, and of the seven scaling parameters on long-term survival of the patients, was built. It showed that only higher Scr levels (P < 0.0001) and higher R values (P < 0.04) were significant outcome predictors. Kaplan-Meier survival analyses of the patients stratified into two groups, respectively, according to the first quartile of R values (0.0-467.8 Ohm), the fourth quartile of Kt/R values (98-106 ml/Ohm) and the first quartile of Scr levels (0.0-11.6 mg/dl) showed a significantly higher long-term survival in the groups of patients having R values above the first quartile (P < 0.04), Kt/R values below the fourth quartile (P < 0.03) and Scr levels above the first quartile (P < 0.0001). Conclusions. Kt/R, R and Scr were independent significant predictors of long-term-survival in incident HD patients: R is related to the fluid status, whereas Scr, which reflects the lean body mass, seems to suggest that body composition is more important than body weight and/or body mass index. Further work is required to develop these concepts and to translate them into rigorous outcome-based adequacy targets suitable for clinical usage.

BACKGROUND The accurate measurement of total body water (TBW) requires isotopic dilution techniques that are not easily applicable to the clinical setting. Therefore, indirect methods of estimating TBW are commonly employed, such as bioelectrical impedance analysis (BIA) and anthropometry. In the human body, >90% of the measured impedance is composed of resistance (R). METHODS The aim of the present study was to compare TBW estimated by means of two anthropometric equations (by Watson and Hume) with TBW obtained by BIA (equations proposed by Sun et al.) in a group of white disease-free individuals (n = 3625, 1860 men and 1765 women) and white haemodialysis (HD) patients (n = 688, 443 men and 245 women). They underwent one single-frequency BIA measurement, on the nondominant side of the body, injecting an 800-muA and 50-kHz alternating sinusoidal current with a standard tetrapolar technique. The BIA variable measured was R. RESULTS Among them, a selection of disease-free individuals (n = 481) and HD patients (n = 270), pair-matched by age, body weight and height, after stratification by gender, was made. When comparing the four pair-matched groups, it was found that (1) TBW was not different (disease-free men versus HD men; disease-free women versus HD women) when using anthropometric equations, which utilize quite identical parameters (age, body weight and height); (2) R was statistically significantly different in the four groups (511 +/- 58 SD Omega in disease-free men versus 558 +/- 80 in HD men, P < 0.0001; 593 +/- 70 Omega in disease-free women versus 615 +/- 100 in HD women, P < 0.02) and (3) therefore, TBW was statistically significantly different only when applying BIA equations (P < 0.0001 and 0.05, respectively). CONCLUSIONS The present study demonstrates that anthropometric equations for the estimation of TBW can be used only within a specific population in order to assess individual differences; they cannot be used in order to compare two different populations.

Background. Non-anaemic haemodialysis (HD) patients are potentially more prone to the adverse effects of ultrafiltration-induced haemoconcentration. No study, however, has assessed the effects of dialytic session on haemoglobin (Hb) levels in these patients. Methods. The levels of Hb and total protein before, at the end (T0) and up to 120 min (T120) after the third HD session of the week were compared in non-anaemic (Hb >13 g/dl, n ¼ 14, NOR) and anaemic (Hb ¼ 11–12 g/dl, n ¼ 18, LOW) HD patients. Results. The intradialytic weight loss was similar in the two groups (4.0 ± 0.9 and 4.1 ± 0.9% body weight). During the treatment, Hb levels increased to the same extent in both groups (from 14.4 ± 1.2 to 16.3 ± 1.9 g/dl in NOR, and from 11.4 ± 0.8 to 12.7 ± 0.9 g/dl in LOW) in the presence, presumably, of a smaller plasma volume in NOR, whereas the increment of total protein was greater in NOR (from 7.1 ± 0.2 to 9.6 ± 0.5 g/dl) than in LOW (from 7.3 ± 0.6 to 8.7 ± 0.8 g/dl) (P < 0.0001). At T120, the Hb decline in NOR was almost double that measured in LOW (� 9.2 ± 3.0 vs � 4.7 ± 2.4%, P < 0.001). Consequently, Hb concentration did not differ from the pre-dialytic value in NOR (P ¼ 0.10), but persisted higher in LOW (P < 0.005). The extent of the postdialytic decrement of Hb was inversely related to the total protein values at T0 (r ¼� 0.547, P ¼ 0.0012). Conclusions. This study indicates that in NOR: (i) the extent of intradialytic increment of Hb is limited by a greater intradialytic plasma refilling; (ii) the greater plasma refilling persists after the end of dialysis, with the restoration of pre-dialytic Hb levels within the initial 2 h; and (iii) the force driving this phenomenon resides mainly in the larger changes of total protein concentration.