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Increased arterial hypertension represents a prevalent condition in peritoneal dialysis patients that is often related to volume expansion. Pulse pressure is a robust predictor of mortality in dialysis patients, but its association with mortality is unknown in peritoneal patients. We investigated the relationship between home pulse pressure and survival in 140 PD patients. During a mean follow-up of 35 months, 62 patients died, and 66 experienced the combined event death/CV events. In a crude COX regression analysis, a five-unit increase in HPP was associated with a 17% increase in the hazard ratio of mortality (HR: 1.17, 95% CI 1.08–1.26 p < 0.001). This result was confirmed in a multiple Cox model adjusted for age, gender, diabetes, systolic arterial pressure, and dialysis adequacy (HR: 1.31, 95% CI 1.12–1.52, p = 0.001). Similar results were obtained considering the combined event death–CV events as an outcome. Home pulse pressure represents, in part, arterial stiffness, and it is strongly related to all-cause mortality in peritoneal patients. In these high cardiovascular risk populations, it is important to maintain optimal blood pressure control, but it is fundamental to consider all the other cardiovascular risk indicators, such as pulse pressure. Home pulse pressure measurement is easy and feasible and can add important information for the identification and management of high-risk patients.

An exaggeration of the early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk. The early morning changes in these parameters have not been investigated in the hemodialysis population.In a pilot, single center study including a series of 58 patients we measured the pre-awakening BP and HR surges and the nocturnal dipping of the same parameters as well as other established indicators of autonomic function (weighted 24 h systolic BP and HR variability) and tested their relationship with the left ventricular mass index (LVMI) and with the risk of death over a median follow up of 40 months.The pre-awakening HR surge (r = - 0.46, P = 0.001) but not the corresponding BP surge (r = - 0.1, P = 0.98) was associated with LVMI and the risk of death [HR (1 unit): 0.89, 95% CI 0.83-0.96, P = 0.001]. The link between the pre-awakening HR surge with these outcome measures was robust and largely independent of established risk factors in the hemodialysis population, including the nocturnal dipping of BP. Weighted 24 h systolic BP and HR variability did not correlate with LVMI (all P 0.11) nor with the risk of death (P 0.11) and were also independent of the nocturnal dipping of systolic BP and HR.This pilot study suggests that the low early morning changes in HR, likely reflecting enhanced sympathetic activity, entail a high risk for left ventricular hypertrophy (LVH) and mortality in the hemodialysis population.

Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.

Hyperkalemia is a potential life-threatening condition among chronic kidney disease (CKD) patients. Available estimates of the burden of this alteration in CKD are mainly derived from large administrative databases. Since K measurements in patients in these databases are often dictated by clinical reasons, longitudinal studies including pre-planned measurements of potassium independently of clinical complication/symptoms may produce more reliable estimates of the frequency and the risk factors underlying hyperkalemia in CKD patients. We estimated the prevalence and the incidence of hyperkalemia in a longitudinal study in 752 stages 2–5 CKD patients lasting 3 years and including up to seven pre-planned assessment of key biochemical measurements including K. At baseline, 203 out of 752 patients (27%) had serum K > 5.0 mM/L and 33% had acidosis (HCO3 ≤ 22 mmol/L). Among those without hyperkalemia at baseline (n = 549), 284 patients developed this alteration across the 3-year follow-up. The point prevalence of hyperkalemia rose from 27% (baseline) to 30% (last visit) (P = 0.001). In a multivariate model, hyperkalemia at baseline [odds ratio (OR):7.29, 95% CI 5.65–9.41, P

BACKGROUND AND AIMS Though the current dialysis population is characterized by a better survival, there is a greater burden of cardiovascular comorbidities. These two factors together expose patients to a greater number of diagnostic and therapeutic contrast tests. The European Society of Urogenital Radiology (ESUR) Guidelines on Contrast Agents 10.0 report that there is no need for urgent dialysis after intravascular iodinated contrast agent administration based on the results of the only study that addressed this problem, conducted in 10 patients by Younathan CM and published in the American Journal of Roentgenology in 1994. As far as the use of gadolinium contrast agent in dialysis patients, the recommendation is to try to perform the contrast agent injection prior to and close to the haemodialysis session, and an extra haemodialysis session to remove the contrast agent as soon as possible after it has been administered is recommended. It is now a well-known phenomenon that when there are low-level recommendations, the behaviour of nephrologists is not homogeneous. METHOD We have created a very simple survey (only 10 questions) to explore the behaviour of Italian nephrologists with respect to the administration of contrast agents in dialysis patients. The main information we wanted to obtain concerned the attitude towards the need for a dialysis session after the administration of a contrast agent (iodate or gadolinium), the timing respect to the contrast examination and the duration of the dialysis session. A total of 50 Italian nephrologists of 50 dialysis centres, respectively, responded to the questionnaire. The average number of chronic dialysis patients treated per single centre was 94 (median 80, interquartile range 46–135), meaning that these are representative of a population of at least 5000 haemodialysis patients. RESULTS After intravascular iodinated contrast agent, according to the ESUR guidelines 9 nephrologists (18%) do not perform an additional dialysis, while 34 nephrologists ( 68%) carry out an additional dialysis session (or organize the contrast examination to coincide with the scheduled dialysis session) (Fig. 1). A total of 32 nephrologists (64%) perform a specific dialysis session after magnetic resonance with gadolinium, as indicated in the ESUR guidelines (Fig. 2). In both cases (iodinated contrast agent or gadolinium), 28 nephrologists (56%) schedule the dialysis session within 4 h of the contrast examination (at least 2 h of treatment or complete dialysis session if possible). Remarkably, 10 nephrologists (20%) do not organize a specific dialysis section after MR with gadolinium (Fig. 2). CONCLUSION Our data confirm that in Italy, the majority of nephrologists still carry out an additional dialysis session after the administration of an iodinated contrast agent to avoid the potential risk of delay and adverse effects (intravascular volume expansion, pulmonary edema, depression of myocardial contractility and arrhythmias). Haemodialysis is an expensive procedure, in particular when performed as a nonscheduled emergent treatment at odd hours of the day or night. Further studies are needed to clarify this controversial point.

BACKGROUND AND AIMS Amplified early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk in the general population. The early morning changes in these parameters have not been investigated in the haemodialysis population. METHOD In a pilot, single centre, study including a series of 58 haemodialysis patients we measured the pre-awakening BP and HR surges and the nocturnal dipping of the same parameters as well as other established indicators of autonomic function (weighted 24h systolic BP and HR variability) and tested their relationship with the left ventricular mass index (LVMI) and with the risk of death over a median follow up of 40 months. RESULTS The pre-awakening HR surge (r = –0.46; P = 0.001) was inversely associated with LVMI and the risk of death [HR (1 unit): 0.89, 95% confidence interval: 0.83–0.96; P = 0.001] while the corresponding BP surge largely failed to associate with these outcomes. The link between the pre-awakening HR surge with LVMI and death was robust and largely independent of established risk factors in the haemodialysis population, including the nocturnal dipping of BP. Weighted 24 h systolic BP and HR variability did not correlate with LVMI (all P > 0.11) nor with the risk of death (P > 0.11) and these parameters were also independent of the nocturnal dipping of systolic BP and HR. CONCLUSION This pilot study suggests that the low early morning changes in HR, likely reflecting enhanced sympathetic activity, entail a high risk for LVH and mortality in the haemodialysis population.

BACKGROUND AND AIMS Ambulatory blood pressure monitoring (ABPM), extended to 44h or 48h for the diagnosis of hypertension in end-stage kidney disease (ESKD) patients, is recommended by Consensus Documents of the American Society of Nephrology and the European Renal Association. About 10%–20% of individuals in the general population report sleeping problems and other symptoms during 24 h ABPM. Because the longer recording period (44 or 48 h versus 24 h), the notorious sleeping disturbances and the high symptom burden of the ESKD population, the feasibility of the technique may be limited in this population. However, the large-scale tolerability of ABPM in the haemodialysis population, has never been investigated. METHOD We performed an international survey of feasibility and tolerability of 48 h ABPM in six centres in three European countries. These centres are led by motivated clinical nephrologists, all members of the EURECA-m working group. 48 h ABPM recording was proposed to a large, representative sample of the whole dialysis population of these centres. Well validated instruments (AAMI/ESH/ISO) were applied in all centres. As recommended by the European Society of Hypertension guidelines, recordings were made at 15-min intervals during the day and 30 min during the night. Reasons for refusal to undergo the test were accurately registered. A tolerability (symptoms) questionnaire and a specific questionnaire for sleep evaluation were administered to all participants who underwent 48h ABPM. Reasons for not completing of the ABPM monitoring were systematically recorded. RESULTS In the whole haemodialysis population of participating centres including 735 patients, 440 (60%) were invited to participate in the study. Among these patients, 119 (27%) refused to undergo ABPM recording. Reasons for refusal were fear of discomfort (n = 30, 25%), measurement too long (n = 22, 18%), logistic problems (n = 17, 14%), previous negative experience (n = 13, 11%), clinical reasons (n = 12, 10%), other reasons (n = 25). Among the 321 patients who performed the 48h ABPM recording, 29 (9%) did not complete it and the main reason for interrupting the recording were discomfort [12 patients (41%)], followed by device failure [10 patients (34%)]. Among symptoms developed during the ABPM study, frequent interruption of sleeping because of noise or discomfort was reported by 32% of patients, followed by itching (24%) and pain during the measurements (20%). The detailed list of symptoms, is reported in the Table 1. CONCLUSION Overall, about 25% of haemodialysis patients consider 48h ABPM a laborious and discomforting test and prejudicially refuse to undergo it. Among patients who undergo 48h ABPM, itching and interruption of sleeping are complained by about 1/3 of patients. These figures are substantially higher than those reported in studies in the general population and in hypertensive patients and point to peculiar barriers at applying extended ABPM recordings in the haemodialysis population. Studies applying more tolerable instruments and a minimum set of measurements over a shorter time, with a reduced number of measurements overnight, are clinical research priority for extending the use of ABPM in the haemodialysis population.

Background Lung ultrasound (US) reliably estimates lung water and it is increasingly applied in clinical practice in dialysis patients. A semi-quantitative US score summing up the US-B lines (an equivalent of B lines in the standard chest X-ray) at 28 sites in the intercostal spaces (Jambrik et al. Usefulness of ultrasound lung comets as a non-radiologic sign of extravascular lung water. Am J Cardiol 2004; 93: 1265–1270) is the most used score. Methods We compared the prognostic performance for death, and cardiovascular (CV) events of the 28-sites US score with a score restricted to eight sites in a cohort of 303 haemodialysis (HD) patients. Results The 8- and the 28-sites scores were highly inter-related (Spearman’s ρ = 0.93, P Conclusion The 8-sites score is tightly related to the classical Jambrik 28-sites score and this score holds an almost identical predictive power to the reference score. Even though the 28-sites score can be completed just in ∼3 min, the 8-sites score requires only ∼1.30 min, and it is, therefore, better suited for application in everyday clinical practice in HD units.

Introduction Since infammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifer of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients. Objective and methods We investigated the efect modifcation by systemic infammation (serum CRP) on the relationship between a surrogate of the flling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantifed by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model. Results At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r=0.23, P

Blood pressure changes upon standing reflect a hemodynamic response, which depends on the baroreflex system and euvolemia. Dysautonomia and fluctuations in blood volume are hallmarks in kidney failure requiring replacement therapy. Orthostatic hypotension has been associated with mortality in hemodialysis patients, but neither this relationship nor the impact of changes in blood pressure has been tested in patients on peritoneal dialysis. We investigated both these relationships in a cohort of 137 PD patients. The response to orthostasis was assessed according to a standardized protocol. Twenty-five patients (18%) had systolic orthostatic hypotension, and 17 patients (12%) had diastolic hypotension. The magnitude of systolic and diastolic BP changes was inversely related to the value of the corresponding supine BP component (r&nbsp, = −0.16, p = 0.056 (systolic) and r&nbsp, = −0.25, p = 0.003 (diastolic), respectively). Orthostatic changes in diastolic, but not in systolic, BP were linearly related to the death risk (HR (1 mmHg reduction): 1.04, 95% CI 1.01–1.07, p = 0.006), and this was also true for CV death (HR: 1.08, 95% CI 1.03–1.12, p = 0.001). The strength of this association was not affected by further data adjustment (p ≤ 0.05). These findings suggest that independent of the formal diagnosis of orthostatic hypotension, even minor orthostatic reductions in diastolic BP bear an excess death risk in this population.

Background and Aims Effective outpatient organization is essential in the management of patients with chronic kidney disease. Although peritoneal dialysis (PD) has many advantages it is still not popular. Method The aim of this study was to evaluate patient and center-related factors that affect the final choice of peritoneal dialysis (PD) versus hemodialysis (HD) in the Calabrian region (Italy). We analyzed 2 annual regional surveys performed by nephrologists (2017 and 2018) in incident dialysis patients. Collected factors included: early and late referral to the dialysis program, pre-dialysis participation in outpatient visits, first dialysis access [peritoneal catheter (PC), central venous catheter (CVC), arteriovenous fistula (AVF)], final dialysis treatment (HD or PD) and the care giver. Results The study sample included 296 incident patients (63% males) aged 66±15 years. Time to referral influenced the type of first dialysis access. Among patients with early referral, 35% initiated dialysis by a PC, 34% by AVF and 31% by CVC, while among those with late referral, only 5% started dialysis by a PC, 15% by AVF, and the majority (80%) by CVC (P Conclusion These data confirm that a more attentive and dedicated organization of the pre-dialysis outpatient program would contribute to a greater expansion of the peritoneal dialysis program.

Background and Aims Lung ultrasound (US) is a reliable method for the identification of patients with lung congestion in the hemodialysis population (JACC Cardiovascular Imaging 2010;3:586-94) and a high number of US-B lines (an equivalent of B lines in the chest X-ray) is a powerful predictor of death and cardiovascular events in this population (JASN 24:639–646, 2013.) .US-B lines are strongly related with the Left Ventricular filling pressure (capillary wedge pressure) and may also be potentially useful for the identification of patients with low blood volume at risk for dialysis hypotension. With this background in mind, in the frame of the “LUng water by Ultra-Sound Guided Treatment (LUST) to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial” (NCT02310061) we investigated, as a secondary study end-point, whether the systematic use of lung US may mitigate the risk of dialysis hypotension. Method We included in this analysis 377 HD patients. In patients in the active arm of the trial (n=197) dialysis ultrafiltration prescription was guided by lung US while in the control arm (n=180) ultrafiltration was prescribed on the basis of standard clinical criteria. The duration of the trial was 2 years. Hypotensive episodes during dialysis were pre-defined as a reduction in mean arterial pressure of >20%, associated with typical symptoms (light-headedness, sweating, nausea and/or vomiting). Incident rate was expressed as number of hypotensive episodes/patient/year. Negative binomial regression (Biometrics. 2014;70:920-31) was applied to analyse the association between US-B lines and the incidence rate of dialysis hypotension. Since a high degree of lung congestion and/or a high variability in lung congestion over time may predispose to dialysis hypotension, in the active arm we also tested the relationship between the average number of US-B lines and the standard deviation (SD) of the same parameter across the trial (2733 pre-dialysis lung US recordings) and the risk of dialysis hypotension. Results During the trial, 890 hypotensive episodes occurred in the active arm and 1292 in the control arm. The corresponding incidence rates were 3.15/patient/yr and 4.73/patient/yr, respectively, with an Incident Risk Ratio of 0.66 (95% CI: 0.61-0.72, P Conclusion Findings in this study show that lung US is a safe method to guide the prescription of dialysis ultrafiltration. Indeed, the systematic application of this technique reduced the risk of dialysis hypotension by the 34%. The finding in the active arm of the trial that a higher number of US-B lines underlies an excess risk of dialysis hypotension suggests that special care should be applied to tailor ultrafiltration in patients with lung congestion to minimize the risk of this outcome.

Background and Aims The knowledge of the impact of peritoneal dialysis (PD) program in terms of hospitalization rate can provide solid guidance for nephrologists for management purpose. In a historical cohort of adult PD patients, we examined the hospitalization rates and causes of hospital admissions. Method One hundred ninety-one consecutive PD patients between January 1st 2000 to December 31st 2018 were enrolled. The maximum follow up was 194 months. Their mean age was 65±15 years, 110 were males, 56 had co-morbidities and 67 were diabetics. The median PD vintage was 35 months (interquartile range 20-63 months). Results During the follow-up, 163 out of 191 patients (85%) underwent hospital admission for a total of 356 hospitalizations [57 hospitalizations per 100-person-years]. The most frequent cause of admission was infection (20 hospitalizations per 100-person-years) mainly due to peritonitis (12 hospitalizations per 100-person-years) followed by cardiovascular diseases (17 hospitalizations per 100-person-years). Hospitalizations due to miscellaneous causes were 21 per 100-person-years. In the whole group, high NYHA score [Incidence Rate Ratio (IRR): 1.52, 95%CI 1.21-1.89, P65 years) (IRR 1.26, 95%CI 1.02-1.56, P=0.03) and were associated to all-cause hospitalizations. In an analysis by hospitalization type, the factors related to admission for infection diseases was malnutrition (IRR: 1.91, 95%CI 1.16-3.03, P=0.005) and high NYHA score (IRR: 1.52, 95%CI 1.03-2.22, P=0.02). As expected, hospitalizations due to cardiovascular causes were strongly related to older age (>65 years) (IRR 2.02, 95%CI 1.35-3.03, P Conclusion Analyzing the causes and the rate of hospitalization in PD patients allows more accurate management of these high risk category of patients and contributes to a more efficient organization of a renal department.

Background and Aims A 21 year old boy with a diagnosis of Autosomal Recessive Polycystic Kidney Disease and Caroli disease reached a final stage of chronic kidney disease (CKD) and started haemodialysis. Method After 3 years in haemodialysis he underwent a kidney transplant from a cadaveric donor. His transplanted kidney worked fairly well until the patients was 31 year old when he developed graft dysfunction (serum creatinine from 2.7 to 5 mg/dL in a very short period). There was a concomitant increase in serum phosphate levels (8.3 mg/dl) and iPTH that progressively increased to 1032 pg/ml despite a traditional therapy. Results At age 32, the patient returned to haemodialysis treatment thrice weekly with a concomitant a progressive worsening of hyperparathyroidism with bone pain . Cinacalcet at a dosage of 30 mg daily treatment was initiated, then it was increased to 120 mg daily without any benefit. Two years later, being the clinical situation without any improvement and being the patient scarcely compliant to the therapy and because a further enlargement of parathyroid glands was observed, a Parathyroidectomy (PTX) was advised. Nevertheless, PTX was not performed because of patient’s refusal. Furthermore, despite Erythropoietic Stimulating Agent (ESA) therapy, he developed severe anemia that required regular and frequent blood transfusions. iPTH increased to 4500 pg/ml [Fig.1] with a parallel rise in alkaline phosphatase >600 UI/L [Fig.2]. A Computed Tomography scan showed multiple bone-thickening lesions. He thus initiated Etelcalcetide 5 mg e.v. 3 times a week, after the HD session but without any benefit. The dosage was then increased to 7.5 mg but the patient gradually became frail and developed pancytopenia and low-grade fever. Hematological evaluation with bone marrow biopsy was performed in December 2019. Bone marrow histology showed severe fibrosis [Myelofibrosis (MF) grade 3] with normal bone marrow cytogenetics. Blood samples for mutations in JAK-2, CALR, and MPL and BCR-ABL rearrangement were negative. There was no evidence for a myeloproliferative neoplasm (MPN) or metastatic lesions. During the following months, while on a 7,5 mg dose of etalcalcetide, there was a gradual reduction in iPTH [Fig.1] and serum alkaline phosphatase [Fig.2], up to 500 pg/dl and 200 IU/L respectively. The patient developed asymptomatic, often severe, hypocalcemia which was managed with therapy. The patient’s clinical conditions gradually improved, anemia responded to lower doses of ESAs. A bone marrow biopsy was repeated after one year (December 2020) and it showed a reduction in fibrosis (MF grade varying from 1-2). Then etelcalcetide dosage was reduced while serum calcium and phosphate levels were in the normal limit. Conclusion Myelofibrosis secondary to renal osteodystrophy is an uncommon complication. It has been rarely reported and usually is associated with primary hyperparathyroidism. Marrow fibrosis and pancytopenia is related to the excessive iPTH that upregulates production of cytokines and paracrine factors in the bone marrow (IL-1a, IL-6, FNF-a, TGF–b, and platelet-derived growth factor) and it has an important stimulatory effect on fibroblast proliferation. It is known that surgical parathyroidectomy is associated with a reduction of bone marrow fibrosis in primary hyperparathyroidism. To our knowledge, this is probably the first case of tertiary hyperparathyroidism in which the effect of etelcalcetide is comparable to parathyroidectomy as far as on calcium-phosphate balance, and a significant improvement in bone marrow fibrosis and hemoglobin. In conclusion, etelcalcetide at least in this patient seems as effective as PTX on bone balance, bone marrow and anemia.

Background Uncontrolled hypertension notwithstanding the use of at least three drugs or hypertension controlled with at least four drugs, the widely accepted definition of treatment-resistant hypertension (TRH), is considered as a common problem in the hemodialysis population. However, to date there is no estimate of the prevalence of this condition in hemodialysis patients. Method We estimated the prevalence of TRH by 44-h ambulatory BP monitoring (ABPM) in 506 hemodialysis patients in 10 renal units in Europe included in the registry of the European Renal and Cardiovascular Medicine (EURECAm,), a working group of the European Association, European Dialysis and Transplantation Association (ERA EDTA). In a sub-group of 114 patients, we tested the relationship between fluid overload (Body Composition monitor) and TRH. Results The prevalence of hypertension with 44-h ABPM criteria was estimated at 85.6% (434 out of 506 patients). Of these, 296 (58%) patients were classified as uncontrolled hypertensive patients by 44-h ABPM criteria (≥130/80 mmHg). Two hundred and thirteen patients had uncontrolled hypertension while on treatment with less than three drugs and 210 patients were normotensive while on drug therapy (n = 138) or off drug treatment (n = 72). The prevalence of TRH was 24% (93 among 386 treated hypertensive patients). The prevalence of predialysis fluid overload was 33% among TRH patients, 34% in uncontrolled hypertensive patients and 26% in normotensive patients. The vast majority (67%) of hemodialysis patients with TRH had no fluid overload. Conclusion TRH occurs in about one in four treated hypertensive patients on hemodialysis. Fluid overload per se only in part explains TRH and the 67% of these patients show no fluid overload.

Background Sleep‐disordered breathing ( SDB ) is considered a strong risk factor for hypertension in the general population. This disturbance is common in end‐stage kidney disease patients on long‐term hemodialysis and improves early on after renal transplantation. Whether SDB may be a risk factor for hypertension in renal transplant patients is unclear. Methods and Results We investigated the long‐term evolution of simultaneous polysomnographic and 24‐hour ambulatory blood pressure (BP) monitoring recordings in a cohort of 221 renal transplant patients. Overall, 404 paired recordings were made over a median follow‐up of 35 months. A longitudinal data analysis was performed by the mixed linear model. The apnea‐hypopnea index increased from a median baseline value of 1.8 (interquartile range, 0.6–5.0) to a median final value of 3.6 (interquartile range, 1.7–10.4; P =0.009). Repeated categorical measurements of the apnea‐hypopnea index were directly associated with simultaneous 24‐hour, daytime, and nighttime systolic ambulatory BP monitoring (adjusted analyses; P ranging from 0.002–0.01). In a sensitivity analysis restricted to 139 patients with at least 2 visits, 24‐hour, daytime, and nighttime systolic BP significantly increased across visits ( P SDB (n=40), whereas the same BP metrics did not change in patients (n=99) with stable apnea‐hypopnea index. Conclusions In renal transplant patients, worsening SDB associates with a parallel increase in average 24‐hour, daytime, and nighttime systolic BP . These data are compatible with the hypothesis that the link between SDB and hypertension is causal in nature. Clinical trials are, however, needed to definitively test this hypothesis.

Background and Aims Lung Ultrasound (US) reliably estimates lung water and it is increasingly applied in clinical practice in dialysis patients. Lung water is currently measured by applying a semi-quantitative US score summing up the US-B lines (an equivalent of B lines in standard X-rays of the thorax) detected in 28 lung intercostal spaces (LIS) (Jambrik Z et al., Am J Cardiol 2004; 93:1265-70). A simplified assessment restricted to 8 LIS only (Gutierrez M et al., Arthritis Research & Therapy, 2011;13:R134) has been proposed. However, the agreement among this simplified score and the reference score has not been studied and the prognostic value of the simplified score (8-LIS) has not been face to face compared with the 28-LIS score. Method We included in the analysis in a cohort of 303 hemodialysis (HD) patients in which the pre-dialysis US-BL score was measured at baseline with both the semi-quantitative by Jambrik and the simplified Gutierrez method. The time needed for performing the 28-LIS and the 8-LIS score by six independent assessors with various experience -from low to high- on lung US assessment was accurately measured and recorded. Patients were divided into 4 categories, according to pre-established cut-offs specific for the two methods (28-LIS score: 30 US-BL; 8-LIS score: 50 US-BL) The prediction power of these scores for death and fatal and non-fatal cardiovascular events was assessed by the explained variance (R2). Results The 28-LIS score and the 8-LIS score were highly inter-related (Spearman’s ρ=0.93, P Conclusion The simplified Gutierrez 8-LIS score is tightly related to the classical Jambrik 28 LIS score and the two scores hold an almost identical predictive power. Even though the 28-LIS score demands less than 5 minutes, the 8-LIS score can be done in only about 90 sec. and it is therefore better suited for application in everyday clinical practice in hemodialysis units.

Background and Aims Cardiovascular deaths cluster in the early morning hours and studies in the general population documented that an exaggeration of the early morning increase in BP, a phenomenon accompanied by a parallel rise in heart rate (HR), is a marker of high cardiovascular risk. The circadian profile of BP and HR in hemodialysis patients is notoriously altered but the early morning changes in these parameters and the nocturnal profile of HR have not been investigated in this population. Method BP and HR were registered at 15 min intervals by ambulatory monitoring (24hABPM, Spacelab) during the day after hemodialysis in a series of 64 patients. We measured the early morning (the average of the 2 hours after awakening minus the average of the 2 hours pre-awakening) changes in BP and HR and the nocturnal decline in BP and HR and tested the relationship of these parameters with the left ventricular mass index (LVMI) and with the risk of all-cause and cardiovascular death over a median follow up of 40 months (Interquartile range 21-81) Results The rise in HR after awakening was strongly related in an inverse fashion with the LVMI (Spearman ρ=-0.61, P Conclusion The analysis of the nocturnal decline in HR and of the rise in HR increase upon awakening In hemodialysis patients reveals stronger links among these parameters and LVMI than the corresponding BP parameters. The protective effect on the left ventricle of a more pronounced HR rise upon awakening and of a more pronounced decline in HR during night time underscore the relevance of preserved autonomic function for cardiovascular protection in this population. These associations seem to go along with a reduced risk for all-cause and cardiovascular death. Analysis of the HR profile provides unique information for the risk of cardiomyopathy and cardiovascular events in the hemodialysis population.

Background and Aims Mortality risk is very high in the dialysis population and the Charlson Comorbidities Index (CCI) is considered as an useful risk stratification tool in these patients. The purpose of this study was to examine the accuracy of CCI for predicting mortality in peritoneal dialysis (PD) patients and to compare the prognostic power of CCI with that of a risk prediction model jointly including a clinical score of malnutrition and the NYHA classes. Method We analyzed this problem in a series of 66 consecutive PD patients on follow-up in our unit. Their mean age was 69±14 years, 64% were male, 36% were diabetic. The median dialysis vintage was 39 months (Interquartile range 23-67 months). Results During follow-up period, 37 patients died. On univariate Cox regression analysis, CCI largely failed to predict mortality [Hazard ratio (HR): 1.08, 95% CI: 0.94-1.24, P=0.30) and this relationship did not improve (HR: 0.93, 95% CI: 0.79-1.08, P=0.32) also after data adjustment for malnutrition and NYHA classes. In the same model, malnutrition (HR: 1.98, 95% CI 1.20-3.27, P=0.007) and NYHA classes (HR: 3.15, 95% CI 1.67-5.94, P Conclusion In this study, CCI did not predict survival in PD patients whereas malnutrition and NYHA score displayed a relevant prognostic accuracy for death in the same patient-population. These results generate the hypothesis, to be confirmed in a larger PD population, that CCI solely for risk stratification is unwarranted in PD patients.

Sleep disordered breathing (SDB), as defined by the Apnea Hypopnea Index (AHI), is a highly prevalent disturbance in end stage kidney disease. SDB improves early on after renal transplantation but long-term changes in AHI in these patients have not been studied. We studied the long-term changes in AHI in a series of 221 renal transplant patients (mean age: 47 &plusmn, 12 years, 70% males) over a median follow up of 35 months. Data analysis was made by the generalized estimating equations method (GEE). On longitudinal observation, the median AHI rose from 1.8 (Interquartile range: 0.6&ndash, 5.0) to 2.9 (IQR: 1.0&ndash, 6.6) and to 3.6 (IQR: 1.7&ndash, 10.4) at the second and third visit, respectively (p = 0.009 by the GEE model and the proportion of patients with moderate to severe SDB rose from 8% to 20%. Longitudinal changes in minimum oxygen saturation (minSaO2) mirrored those in the AHI. In adjusted analyses, repeated measurements of BMI (p &lt, 0.009) emerged as the strongest independent longitudinal correlate of AHI and MinSaO2. The AHI worsens over time in renal transplant patients and longitudinal changes of this biomarker are directly related to simultaneous changes in BMI. Overweight/obesity, a potentially modifiable risk factor, is an important factor underlying the risk of SDB in this population.

Background and Aims According to local resources, different vascular access (VA) procedures are employed in every country. In Italy, high variability exists in VA management among different dialysis units. In 2018, the DOPPS 5 study showed a declining prevalence of lower arm arteriovenous fistulas (AVF) in Europe with an increasing tendency of making upper arm AVFs and placing central venous catheters (CVCs). Accordingly, an Italian Survey in 2013 confirmed an increasing trend in CVCs use among different Italian regions. Hence, we made an epidemiologic, multicenter study to evaluate a possible relation between this trend and the variability of local VA management policies. Method VA data from 236 patients of prevalent patients were collected from five dialysis centers in the South of Italy. The prevalence of the various types of VAs was analyzed in relation to the following different VA surgery policies adopted in the participant centers: Results Age of patients was comparable among all centers while dialysis vintage was higher in center A (P Conclusion The reduced tendency of lower arm fistulas and the increasing prevalence of CVCs showed by the DOPPS 5 study might not be applicable to all Italian regions. In our study of 5 dialysis units in the South of Italy, the stability of the nephrologist’s surgical activity probably played a crucial role in explaining the observed decreased use of CVCs with a steadily high prevalence (over 70%) of the lower arm fistulas, regardless of aging.

BACKGROUND The parathyroid glands are endowed both with receptors responsive to FGF23 and to 1,25 vitamin D. Vitamin D receptor (VDR) activation, besides lowering PTH, also raises serum FGF23. FGF23 has been implicated in parathyroid resistance to VDR activation but the issue has never been investigated in predialysis CKD patients. METHODS In the Paricalcitol and Endothelial Functio in Chronic Kidney Disease (PENNY) study (NCT01680198), a 12-week randomized trial in stage G3-4 CKD patients (placebo n = 44 and paricalcitol n = 44), we measured PTH and the active form of FGF23 with no missing value across the trial. RESULTS At baseline, serum FGF23 and PTH were inter-related (r = .54, P

Background Renal transplant patients have a high prevalence of nocturnal hypertension, and hypertension misclassification by office blood pressure (BP) is quite common in these patients. The potential impact of hypertension misclassification by office BP on hypertension management in this population has never been analysed. Methods We performed a longitudinal study in a cohort of 260 clinically stable renal transplant patients. In all, 785 paired office and 24-h ambulatory blood pressure monitoring (24-hABPM) measurements over a median follow-up of 3.9 years were available in the whole cohort. Results A total of 74% of patients had nocturnal hypertension (>120/70 mmHg). Average office BP and 24-hABPM remained quite stable over follow-up, as did the prevalence of nocturnal hypertension, which was 77% at the last observation. However, the global agreement between office BP and average 24 h, daytime and night-time BP was unsatisfactory (k-statistics 0.10–0.26). In 193 visits (25% of all visits) where office BP indicated the need of antihypertensive therapy institution or modification (BP >140/90 mmHg), 24-hABPM was actually normal ( Conclusions Hypertension misclassification by office BP is a common phenomenon in stable renal transplant patients on long-term follow-up. Office BP may lead to inappropriate therapeutic decisions in over one-third of follow-up visits in these patients.

OBJECTIVES Hypertension is a risk factor for renal function loss in kidney transplant patients but there are still no longitudinal studies focusing on the relationship between ambulatory blood pressure (BP) monitoring (ABPM) and the glomerular filtration rate (GFR) evolution over time in these patients. METHODS In a cohort of 260 renal transplant patients, we investigated the longitudinal relationship between repeated office BP measurements and simultaneous GFR measurements (on average 35 paired measurements per patient) and the relationship between baseline ABPM with the same outcome measure (by linear mixed models). Furthermore, we tested the prediction power of baseline ABPM and standardized BP measurements for a combined renal end point (GFR loss >30%, end-stage kidney disease or death) over a 3.7 years follow-up. RESULTS Longitudinal office BP measurements were inversely related with simultaneous GFR measurements and the same was true both for baseline daytime and night-time BP. (all P

Background Population-specific consensus documents recommend that the diagnosis of hypertension in haemodialysis patients be based on 48-h ambulatory blood pressure (ABP) monitoring. However, until now there is just one study in the USA on the prevalence of hypertension in haemodialysis patients by 44-h recordings. Since there is a knowledge gap on the problem in European countries, we reassessed the problem in the European Cardiovascular and Renal Medicine working group Registry of the European Renal Association-European Dialysis and Transplant Association. Methods A total of 396 haemodialysis patients underwent 48-h ABP monitoring during a regular haemodialysis session and the subsequent interdialytic interval. Hypertension was defined as (i) pre-haemodialysis blood pressure (BP) ≥140/90 mmHg or use of antihypertensive agents and (ii) ABP ≥130/80 mmHg or use of antihypertensive agents. Results The prevalence of hypertension by 48-h ABP monitoring was very high (84.3%) and close to that by pre-haemodialysis BP (89.4%) but the agreement of the two techniques was not of the same magnitude (κ statistics = 0.648; P Conclusions The prevalence of hypertension in haemodialysis patients assessed by 48-h ABP monitoring is very high. Pre-haemodialysis BP poorly reflects the 48 h-ABP burden. About a third of the haemodialysis population has white coat or masked hypertension. These findings add weight to consensus documents supporting the use of ABP monitoring for proper hypertension diagnosis and treatment in this population.

Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide efficacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in &ldquo, real world&rdquo, setting that is different from randomized controlled trials (RCTs) to (1) evaluate the effectiveness of etelcalcetide in SHPT, (2) to assess calcium, phosphorus, alkaline phosphatase changes, (3) to register gastrointestinal side effects. Data were collected from twenty-three dialysis units with n = 1190 patients on the charge. From this cohort, n = 168 (14%) patients were on treatment with etelcalcetide, and they were evaluated for statistics. A median weekly dose of etelcalcetide was 15 mg (7.5&ndash, 45 mg). Patients were either na&iuml, ve (33%) or switched from cinacalcet to obtain better control of SHPT with reduced side effects or pills burden. Serum parathyroid hormone (PTH) declined over time from a median value of 636 pg/mL to 357 pg/mL. The median time for responders (intact PTH (iPTH) range: two to nine times the upper normal limit) was 53 days, the percentage of responders increased (from baseline 27% to 63%) being similar in switched-patients and na&iuml, ve-patients. Few patients had symptomatic hypocalcemia requiring etelcalcetide withdrawal (four cases (3%) at 30-day control, two cases (2%) at 60-day, one case (1%) at 90-day control). Side effects with etelcalcetide were lower (3&ndash, 4%) than that registered during cinacalcet treatment (53%). Etelcalcetide is a new therapeutic option for SHPT with low side effects and pills burden. Etelcalcetide may improve adherence to therapy, avoiding unremitting SHP. It remains to be assessed whether etelcalcetide may reduce parathyroidectomy, vascular calcification, or mortality. Being etelcalcetide very potent in suppressing PTH levels, even in severe SHPT, future studies should evaluate the potential risk of more adynamic bone disease during long-term therapy.

Lung congestion and frank pulmonary edema are established complications of acute kidney injury (AKI) and early detection and monitoring of lung congestion may be useful for the clinical management of AKI patients.We compared standardized clinical criteria (including lung crackles and peripheral edema grading) and simultaneous chest ultrasound (US) to detect lung congestion in a series of 39 inpatients with AKI.At baseline, twelve patients (31%) were clinically euvolemic and twelve presented clear-cur cardiovascular congestion (31%) by clinical criteria. Fifteen patients (38%) were hypovolemic. The median number of US-B lines in patients with cardiovascular congestion was much higher (50, inter-quartile range 27-99) than in euvolemic (14, IQR 11-37) and hypovolemic patients (7, IQR 3-16, P 0.001). Remarkably, a substantial proportion of asymptomatic euvolemic (66%) and hypovolemic (46%) patients had lung congestion of moderate to severe degree ( 15 US-B lines) by lung US. Crackles severity and the number of US-B lines over time were inter-related (Spearman's ρ = 0.38, P 0.01) but the agreement (Cohen k statistics) between the two metrics was unsatisfactory. Forty-eight percent of patients had lung congestion of moderate to severe degree by lung US and this estimate by far exceeded that by clinical criteria (32%).This pilot study shows that chest US has potential for the detection of lung congestion at a pre-clinical stage in AKI. The results of this pilot study form the basis for a clinical trial testing the usefulness of this technique for guiding lung congestion treatment in patients with AKI.

Background Excessive sodium intake is a risk factor for hypertension, cardiovascular disease and the risk for kidney failure in chronic kidney disease (CKD) patients. Methods We tested the diagnostic performance and the feasibility of an inexpensive method based on urine chloride strips for self-monitoring sodium intake in a series of 72 CKD patients. Results Twenty-four hour urinary chloride as measured by the reactive strips and 24 h urinary sodium were interrelated (r=0.59, p100 mmol/24 h, i.e. the upper limit recommended by current CKD guidelines. The strip method had 75.5% sensitivity and 82.6% specificity to correctly classify patients with urine sodium >100 mmol/24 h. The positive and the negative predictive values were 90.2% and 61.3%, respectively. The overall accuracy (ROC curve analysis) of urine chloride self-measurement for the >100 mmol/24 h sodium threshold was 87% (95% CI: 77%–97%). The large majority of patients (97%) perceived the test as useful to help compliance with the prescribed dietary sodium and considered the test as simple and of immediate application (58%) or feasible but requiring attention (39%). Conclusions A simple and inexpensive test for urine chloride measurement has a fairly good performance for the diagnosis of excessive sodium intake. The test is feasible and it is perceived by CKD patients as helpful for enhancing compliance to the dietary sodium recommendations. The usefulness of this test for improving hypertension control in CKD patients will be tested in a clinical trial (Clinicaltrials.gov RF-2010-2314890).

Background Old patients with end-stage kidney disease (ESKD) represent an increasing segment of the ESKD population maintained on chronic dialysis treatment. Quality of life (QoL) is notoriously poor in ESKD but relationship between QoL and mortality has not been investigated in the old dialysis population. The objective of this study is to investigate the relationship between QoL and mortality in the old dialysis population. Methods Quality of Life was measured by the Rand- QoL Short Form 36 questionnaires in a multicentre, perspective cohort study including 253 very old patients (age ≥ 75 years) on chronic dialysis. Prognostic power of QoL was assessed applying C-statistics. Results In multivariate statistical models including a series of demographic and clinical variable physical function and general health maintained an independent relationship with survival (P ≤ 0.01). In analyses testing the prognostic value of these two SF36 components physical functioning was the component adding the highest explanatory power to standard demographic and clinical risk factors (+5.7%). Furthermore, the same parameter increased by 4.5% the discriminant power by the Harrell’s C Index, improved risk reclassification by the 20% (P = 0.003) and model calibration by the 83%. Conclusions In the very old dialysis population the physical function component of the SF36 is the QoL component holding the highest predictive power for mortality among the eight components of this instrument. As the discrimination power and risk reclassification ability by physical functioning is of degree relevant for clinical practice, such a measure has potential for refining prognosis and informing exercise programs in this population.

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

In patients with nephrotic syndrome (NS), the lung is considered an organ protected from the risk of edema. However, data on objectively measured lung water in NS patients is lacking. Here we measured lung water by an ultrasound (US) technique as well as by transthoracic impedance in 42 asymptomatic patients with active NS, in 14 stage G5D CKD patients on chronic hemodialysis, and in 21 healthy individuals. In patients with active NS, the median number of US-B lines (a metric of lung water) after 5 min in a supine position was significantly higher (12; interquartile range: 7-25) compared with that in healthy individuals (4; 2-9) but similar to that in hemodialysis patients (23; 10-39). The difference between NS patients and healthy individuals was significantly amplified (16; 10-35 vs. 4; 2-9) after 60 min of supine resting and significantly attenuated after 5 min of standing (10; 7-25 vs. 3; 1-6). Posture-dependent changes in lung water in patients with active NS were significantly accentuated compared with both hemodialysis patients and healthy individuals. After NS remission, the number of US-B lines was significantly reduced to 5 (4-18) at 5 min and to 6 (5-22) at 60 min approaching the normal range. Lung congestion in patients with active NS was confirmed by transthoracic impedance. Thus, asymptomatic pulmonary congestion is pervasive in patients with NS. A clinical trial is needed to assess the utility of lung US for the management of patients with NS.

The authors wish to make the following corrections to the previous publication [...]

Rationale & Objective Hyperphosphatemia is associated with increased risk for chronic kidney disease (CKD) progression and reduced antiproteinuric effects of renin-angiotensin system (RAS) blockers. We investigated whether the phosphate binder sevelamer carbonate may enhance the antiproteinuric effect of RAS inhibitors in patients with CKD. Study Design Phase 2, randomized, controlled, open-label, crossover trial. Setting & Participants Between November 2013 and December 2014, we enrolled 53 patients with CKD with estimated glomerular filtration rates (eGFRs)>15mL/min/1.73m2 and residual proteinuria with protein excretion≥0.5g/24h despite maximal tolerated ramipril and/or irbesartan therapy from 2 nephrology units in Italy. Intervention After stratification by serum phosphate level, ≤4 or>4mg/dL, patients were randomly assigned to 3 months of sevelamer (1,600mg thrice daily) treatment followed by 3 months without sevelamer separated by a 1-month washout period or 3 months without sevelamer followed by 3 months with sevelamer, also separated by a 1-month washout period. Outcomes The primary outcome was 24-hour proteinuria (n=49patients). Secondary outcomes included measured GFR (using iohexol plasma clearance), office blood pressure (BP), serum lipid levels, levels of inflammation and bone metabolism biomarkers, urinary electrolyte levels, and arterial stiffness. Results Changes in proteinuria during the 3-month treatment with (from 1.36 [IQR, 0.77-2.51] to 1.36 [IQR, 0.77-2.60] g/24h) or without (from 1.36 [IQR, 0.99-2.38] to 1.48 [IQR, 0.81-2.77] g/24h) sevelamer were similar (P=0.1). Sevelamer reduced urinary phosphate excretion without affecting serum phosphate levels. Sevelamer reduced C-reactive protein (CRP), glycated hemoglobin, and total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol levels without affecting levels of office BP, measured GFR, fibroblast growth factor 23, klotho, intact parathyroid hormone, serum vitamin D, or other urinary electrolytes. Results were similar in the low- and high-phosphate groups. Sevelamer was well tolerated. Adverse events were comparable between treatment periods. One case of transient hypophosphatemia was observed during treatment with sevelamer. Limitations Short treatment duration, lower pretreatment proteinuria than expected. Conclusions 3-month sevelamer treatment did not reduce proteinuria in patients with CKD on maximal RAS blockade. Amelioration of inflammation and dyslipidemia with sevelamer treatment raises the possibility that it may confer benefit in patients with CKD beyond reduction of proteinuria. Funding Sanofi (Milan, Italy). Trial Registration Registered at ClinicalTrials.gov with study number NCT01968759.

BACKGROUND The prognostic relevance of health-related quality of life (HRQoL) has been scarcely studied in the dialysis population and the prognostic power for mortality of the HRQoL domains is unknown. METHODS We tested the prognostic value for mortality of the HRQoL domains included in the 36-item Short Form Health Survey (SF-36) by Cox's regression analysis and by state-of-the-art prognostic techniques {explained variation in mortality [R2], calibration, discrimination [Harrell's C], risk reclassification [Net Reclassification Index (NRI)], Integrated Discrimination Index [IDI]} in a cohort of 951 patients on chronic haemodialysis. RESULTS In multivariable Cox models, all but two domains (role limitation due to physical health and due to emotional problems) were independently related with mortality. Physical functioning was the domain adding the highest explanatory power (R2+5.3%) to a basic model including established risk factors for mortality in the dialysis population. The same domain improved risk calibration and showed the highest Harrell's C (+1.7%) and the highest reclassification power (categorical NRI + 8.7%, continuous NRI +46%, P ≤ 0.006) and the highest IDI (+3.4%, P

BACKGROUND Thrombomodulin (TM) is a proteoglycan highly represented in the endothelial glycocalix that regulates the haemostasis and the endothelial response to inflammation. High soluble TM levels underlie a lower risk for coronary heart disease in population studies. Activation of vitamin D receptor (VDR) upregulates TM, but the effect of this intervention on soluble TM has never been tested in chronic kidney disease (CKD) patients. METHODS We performed a post hoc analysis of a 12 weeks double blind, randomized, placebo-controlled trial testing the effect of VDR activation by paricalcitol (PCT) on endothelium-dependent flow-mediated vasodilatation (FMD) in the forearm (ClinicalTrials.gov identifier: NCT01680198). Circulating TM was measured in the whole CKD population [88 patients: PCT n = 44; placebo n = 44] that took part into this trial. RESULTS Soluble TM at baseline was inversely related to the glomerular filtration rate (r = -0.65, P

Major health agencies now recommend the systematic application of ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension. Given the exceedingly high prevalence of nocturnal hypertension, masked and white coat hypertension and the overt inadequacy of peridialysis (pre-, intra- and post-dialysis) BP measurements, more extensive application of ABPM for the diagnosis of hypertension in dialysis patients would appear logical. In a recent survey performed in NDT Educational, organizational problems and/or cognitive resistance emerged as important factors hindering more extensive application of ABPM and home BP by nephrologists. External validation of observations made in landmark studies in a single institution about hypertension subcategorization by ABPM is urgently needed. Furthermore, apparent cognitive resistance by nephrologists may be justified by the fact that these techniques have been insufficiently tested in the dialysis population for applicability in everyday clinical practice, tolerability, organizational impact and cost-effectiveness. We should be more resolute in abandoning peridialysis measurements for diagnosing and treating hypertension in haemodialysis patients. Home BP is a formidable educational instrument for patient empowerment and self-care, and evidence exists that this technique is superior to peridialysis values to better hypertension control as defined on the basis of ABPM. We should strive to promote more extensive application of home BP monitoring to diagnose and manage hypertension in haemodialysis patients. ABPM with novel, user friendly and better tolerated techniques is to be awaited in the near future.

Background Vitamin D associates with the plasma concentration of the endogenous inhibitor of the nitric oxide system asymmetric dimethyl arginine (ADMA) and cross-sectional studies in CKD patients treated with the vitamin D receptor activator paricalcitol show that plasma ADMA is substantially less than in those not receiving this drug. Methods In the frame of a randomized, double-blind, placebo controlled trial, the Paracalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY), we investigated whether vitamin D receptor activation by paricalcitol (2 μg/day x 12 weeks) affects the plasma concentration of ADMA and symmetric dimethyl arginine (SDMA) in 88 patients with stage 3 to 4 CKD. Results Paricalcitol produced the expected small rise in serum calcium and phosphate and a marked PTH suppression. However, ADMA [Paricalcitol: baseline 0.75 μMol/L (95%CI: 0.70-0.81), 12 week 0.72 μMol/L (95%CI: 0.66-0.78); Placebo: baseline 0.75 μMol/L (95%CI: 0.70-0.90) 12 weeks 0.70 μMol/L (95%CI: 0.66-0.74)] and SDMA [Paricalcitol: baseline 0.91 μMol/L (95%CI: 0.82-1.00), 12 week 0.94 μMol/L (95%CI: 0.82-0.1.06); Placebo: baseline 0.91 μMol/L (95%CI: 0.82-1.06) 12 weeks 0.99 μMol/L (95%CI: 0.88-1.10)] remained unchanged during the trial and 2 weeks after stopping these treatments. Conclusions Paricalcitol does not modify plasma ADMA and SDMA in patients with stage 3-4 CKD. The apparent beneficial effects of paricalcitol on ADMA registered in cross-sectional studies is likely attributable to confounding by indication rather than to a true effect of this drug on ADMA metabolism.

OBJECTIVES Hyperuricemia associates with hypertension, but it is uncertain whether this relationship is causal in nature. Glucose transporter 9 (GLUT9) gene is a major genetic determinant of plasma uric acid levels in humans. Since polymorphisms are randomly distributed at mating (Mendelian randomization), studies based on GLUT9 polymorphisms may provide unconfounded assessment of the nature of the link between uric acid and hypertension. METHODS We tested the association between uric acid, the rs734553 polymorphism of the GLUT9 gene and arterial pressure in a family-based study including 449 individuals in a genetically homogenous population in Southern Italy. RESULTS Serum uric acid levels were strongly associated (P