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Cardiovascular disease is the leading cause of mortality in patients with end-stage-kidney disease. Evidence on the possible echocardiographic differences between hemodialysis and peritoneal dialysis (PD) is scarce. This study aimed to evaluate differences in left (LA) and right atrial (RA), left (LV) and right ventricular (RV) geometry, systolic and diastolic function in hemodialysis, and PD patients. Thirty-eight hemodialysis and 38 PD patients were matched for age, sex, and dialysis vintage. Two-dimensional and tissue-Doppler echocardiography, and lung ultrasound were performed during an interdialytic day in hemodialysis and before a programmed follow-up visit in PD patients. Vena cava diameter (11.09 ± 4.53 vs. 14.91 ± 4.30 mm; p < 0.001) was significantly lower in hemodialysis patients. Indices of LA, RA, LV, and RV dimensions were similar between the two groups. LVMi (116.91 [38.56] vs. 122.83 [52.33] g/m2 ; p = 0.767) was similar, but relative wall thickness was marginally (0.40 [0.14] vs. 0.45 [0.15] cm; p = 0.055) lower in hemodialysis patients. LV hypertrophy prevalence was similar between groups (73.7% vs. 71.1%; p = 0.798), but hemodialysis patients presented eccentric and PD patients concentric LVH. Regarding ventricular systolic function, stroke volume (p = 0.030) and cardiac output (p = 0.036) were higher in hemodialysis, while RV systolic pressure (RVSP) (20.37 [22.54] vs. 27.68 [14.32] mm Hg; p = 0.009) was higher in PD. No significant differences were evidenced in diastolic function indices and lung water excess between the two groups. A moderate association was noted between ultrasound B-lines score and LA volume index (r = 0.465, p < 0.001), RVSP (r = 0.431, p < 0.001), and E/e' ratio (r = 0.304, p = 0.009). Hemodialysis and PD patients present largely similar echocardiographic indices reflecting cardiac geometry, systolic, and diastolic function, but different patterns of abnormal LV remodeling.

BACKGROUND Ambulatory pulse-wave velocity (PWV), augmentation pressure, and augmentation index (AIx) are associated with increased cardiovascular events and death in hemodialysis. The intermittent nature of hemodialysis generates a distinct ambulatory pattern, with a progressive increase of augmentation pressure and AIx during the interdialytic interval. No study so far has compared the ambulatory course of central hemodynamics and PWV between peritoneal dialysis and hemodialysis patients. METHODS Thirty-eight patients under peritoneal dialysis and 76 patients under hemodialysis matched in a 1 : 2 ratio for age, sex and dialysis vintage underwent 48-h ambulatory blood pressure (BP) monitoring with the oscillometric Mobil-O-Graph device. Parameters of central hemodynamics [central SBP, DBP and pulse pressure (PP)], wave reflection [AIx, heart rate-adjusted AIx; AIx(75) and augmentation pressure] and PWV were estimated from the 48-h recordings. RESULTS Over the total 48-h period, no significant differences were observed between peritoneal dialysis and hemodialysis patients in mean levels of central SBP, DBP, PP, augmentation pressure, AIx, AIx(75) and PWV. However, patients under peritoneal dialysis and hemodialysis displayed different trajectories in all the above parameters over the course of the recording: in peritoneal dialysis patients no differences were noted in central SBP (125.0 ± 19.2 vs. 126.0 ± 17.8 mmHg, P = 0.25), DBP, PP, augmentation pressure (13.0 ± 6.8 vs. 13.7 ± 7. mmHg, P = 0.15), AIx(75) (25.9 ± 6.9 vs. 26.3 ± 7.8%, P = 0.54) and PWV (9.5 ± 2.1 vs. 9.6 ± 2.1 m/s, P = 0.27) from the first to the second 24-h period of the recording. In contrast, hemodialysis patients showed significant increases in all these parameters from the first to second 24 h (SBP: 119.5 ± 14.4 vs. 124.6 ± 15.0 mmHg, P

It is unclear whether normal white blood cell (WBC) counts are predictive of subsequent mortality in hemodialysis patients. All patients aged 17 years or more, who initiated hemodialysis at a tertiary Hospital from January 2000 to August 2017 with a dialysis vintage of greater than 90 days and normal median WBC count of their first dialysis year were included in the study. They were followed until they died, transferred to other dialysis facilities, switched to peritoneal dialysis, received a renal transplant or reached the end of the study (August 31, 2018). Cox regression was used to estimate hazard ratios for mortality of tertiles of WBC counts, adjusting for baseline demographic, clinical and laboratory variables. 611 patients [median (interquartile range) age 65.2 (53.3–72.6) years, 62.4% male] were studied. During a median follow-up of 3.9 (1.6–7.2) years, 270 participants died. Patients in the mid- (6.25–7.73 × 103/μL, n = 203) and top-tertile (7.73–10.50 × 103/μL, n = 203) of normal WBC counts had significantly higher mortality than patients in the bottom-tertile (3.50–6.25 × 103/μL, n = 205). The adjusted hazard ratio for mortality relative to the bottom-tertile was 1.54, 95% confidence interval (CI) 1.05–2.25 and 2.20, 95% CI 1.46–3.32, for the mid- and top-tertiles, respectively. In hemodialysis patients, higher WBC count within the normal range is associated with increased long-term mortality. This finding is described for the first time and provides further insight into the clinical significance of a “normal” WBC count result in dialysis patients.

Scientific data regarding intravenous iron supplementation in peritoneal dialysis (PD) patients are scarce. In attempting to administer the minimum monthly IV iron dose that could improve erythropoiesis, we wanted to assess the safety and efficacy of monthly maintenance intravenous administration of 100 mg iron sucrose in PD patients. In a 9-month prospective study, all clinically stable PD patients received intravenously 200 mg of iron sucrose as a loading dose, followed by monthly doses of 100 mg for five consecutive months. Levels of hemoglobin (Hb), ferritin, transferrin saturation (TSAT), reticulocyte hemoglobin content (CHr) and C-reactive protein (CRP) were measured before each administration and 3 months after the last iron infusion. Also, doses of concurrent erythropoietin administration were recorded. Eighteen patients were eligible for the study. Mean levels of Hb and ferritin increased significantly (from 10.0 to 10.9 mg/dL, p = 0.01 and from 143 to 260 ng/mL, p = 0.005), as well as the increase in TSAT levels approached borderline significance (from 26.2 to 33.1%, p = 0.07). During the 6 months of iron administration, the erythropoietin dose was reduced in five patients and discontinued in one. During the 3 months following the last iron infusion, three of them again raised the erythropoietin dose to previous levels. None of the patients experienced any side effects related to IV iron administration. A monthly maintenance intravenous dose of 100 mg iron sucrose may be a practical, effective, and safe in the short term, treatment of anemia in PD patients resulting in improved hemoglobin levels, iron indices, and erythropoietin response.

Aims Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. Methods and results Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re‐evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow‐up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P 50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. Conclusions The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long‐term follow‐up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

Σκοπός της παρούσας μελέτης ήταν η διερεύνηση σε αιμοκαθαιρόμενους ασθενείς της συσχέτισης των επιπέδων στον ορό της φετουΐνης-Α, της οστεοπροτεγερίνης και του FGF-23, με τη σκλήρυνση του αρτηριακού τοιχώματος και την αρχόμενη αθηροσκλήρωση.Στη μελέτη εντάχθηκαν 81 ασθενείς υπό χρόνια αιμοκάθαρση. Τα επίπεδα φετουΐνης-Α, οστεοπροτεγερίνης, άθικτου μορίου FGF-23 (iFGF-23) και καρβοξυτελικού τμήματος (cFGF-23) προσδιορίστηκαν στον ορό με ανοσοενζυμική μέθοδο. Η σκλήρυνση του αρτηριακού τοιχώματος εκτιμήθηκε με τη μέτρηση της ταχύτητας αγωγής σφυγμικού κύματος (PWV) μεταξύ καρωτίδας και μηριαίας αρτηρίας. Η αρχόμενη αθηροσκλήρωση εκτιμήθηκε με την υπερηχογραφική μέτρηση του πάχους του έσω-μέσου χιτώνα (ΙΜΤ) της κοινής καρωτίδας. Η PWV παρουσίασε αρνητική συσχέτιση με την φετουΐνη-Α (p=0,001), και θετική με την οστεοπροτεγερίνη (p=0,000), ενώ δεν παρουσίασε γραμμική συσχέτιση με τα επίπεδα cFGF-23 και iFGF-23. Σε μοντέλο πολλαπλής γραμμικής παλινδρόμησης, τόσο η φετουΐνη-Α όσο και η οστεοπροτεγερίνη παρουσίασαν ανεξάρτητη συσχέτιση με την PWV (p=0,032, standard beta=-0197 και p=0,041, standard beta=0,227 αντίστοιχα). Σε υποομάδα 59 ασθενών χωρίς στεφανιαία νόσο ταχύτητες αγωγής σφυγμικού κύματος < 9,1m/sec, και >11,1m/sec παρουσίασαν θετική συσχέτιση με τα επίπεδα iFGF-23 (p=0,032), η οποία στην πολυπαραγοντική ανάλυση ήταν ανεξάρτητη από την ηλικία, την παρουσία σακχαρώδους διαβήτου, την πίεση σφυγμού και τα επίπεδα φετουΐνης-Α, οστεοπροτεγερίνης (p=0.049). Στη μονοπαραγοντική ανάλυση το ΙΜΤ παρουσίασε αρνητική συσχέτιση με την φετουΐνη-Α (p=0,005), και θετική με την οστεοπροτεγερίνη (p=0,000). Οι συσχετίσεις όμως αυτές δεν ήταν ανεξάρτητες από την ηλικία. Το ΙΜΤ δεν παρουσίασε γραμμική συσχέτιση με τα επίπεδα cFGF-23 και iFGF-23. Όμως υψηλότερα από το μέσο όρο επίπεδα iFGF-23 συσχετίσθηκαν με υψηλότερες τιμές ΙΜΤ (p=0,035). Η συσχέτιση αυτή ήταν ανεξάρτητη από την ηλικία. Στην πολυπαραγοντική ανάλυση ανεξάρτητη συσχέτιση με το ΙΜΤ παρουσίασαν η ηλικία (p=0,000, standard beta=0,570), η παρουσία καρδιαγγειακής νόσου (p=0,031, standard beta=0,166), και τα υψηλότερα σε σχέση με το μέσο όρο επίπεδα iFGF-23 (p=0,028, standard beta=0,164). Σε μοντέλο που περιελάμβανε μόνο τους ορολογικούς δείκτες που συσχετίσθηκαν με το ΙΜΤ ανεξάρτητη συσχέτιση με το ΙΜΤ παρουσίασαν η οστεοπροτεγερίνη (p=0.000, standard beta=0,420), τα επίπεδα iFGF-23 (p=0.016, standard beta=0,232) και η φετουΐνη-Α (p=0.032, standard beta=-0,223). Συμπερασματικά σε ασθενείς υπό χρόνια αιμοκάθαρση η φετουΐνη-Α και η οστεοπροτεγερίνη παρουσίασαν ανεξάρτητη γραμμική συσχέτιση, αρνητική και θετική αντίστοιχα, με τη σκλήρυνση του αρτηριακού τοιχώματος, ως ταχύτητα αγωγής σφυγμικού κύματος (PWV). Η συσχέτισή τους με την αρχόμενη αθηροσκλήρωση ως πάχυνση του αρτηριακού τοιχώματος (IMT) δεν ήταν ανεξάρτητη από την ηλικία.

Innate immunity and chronic inflammation are involved in atherosclerosis and atherothrombosis leading to target organ damage in essential hypertension (EH). However, the role of neutrophils in EH is still elusive. We investigated the association between angiotensin II (Ang II) and neutrophil extracellular traps (NETs) in pathogenesis of EH. Plasma samples, kidney biopsies and surgical specimens of abdominal aortic aneurysms (AAA) from EH patients were used. Cell-based assays, NETs/human aortic endothelial cells co-cultures and in situ studies were performed. Increased plasma levels of NETs and tissue factor (TF) activity were detected in untreated, newly-diagnosed, EH patients. Stimulation of control neutrophils with plasma from untreated EH patients generated TF-enriched NETs promoting endothelial collagen production. Ang II induced NETosis in vitro via a reactive oxygen species (ROS)/peptidylarginine deiminase type 4 and autophagy-dependent pathway. Circulating NETs and thrombin generation levels were reduced significantly in EH patients starting treatment with Ang II receptor blockers, whereas their plasma was unable to trigger procoagulant NETs. Moreover, TF-bearing NETotic neutrophils/remnants were accumulated in sites of interstitial renal fibrosis and in the subendothelial layer of AAA. These data reveal the important pathogenic role of Ang II/ROS/NETs/TF axis in EH, linking thromboinflammation with endothelial dysfunction and fibrosis.

We report the case of a 69-year-old man with uncontrolled multidrug-resistant secondary hypertension following a 10 year history of endovascular abdominal aortic aneurysm repair, with suprarenal fixation and concurrent angioplasty with stenting of the left renal artery for atherosclerotic renal disease, and progressive chronic kidney disease. Renal scintigraphy revealed complete loss of the right kidney's and severe reduction of the left kidney's perfusion and function. Following recent evidence and consultation with vascular surgeons regarding the technical difficulties of any procedure, escalation of antihypertensive treatment was initially chosen. Careful drug adjustments significantly improved but did not fully control blood pressure (BP); further, the patient experienced an acute ischaemic stroke and renal function deterioration towards end-stage renal disease within a few months. At this point, revascularization of the left renal artery coupled with three haemodialysis sessions to remove contrast media was justified as rescue therapy against permanent renal replacement therapy. Successful intervention achieved an immediate BP reduction, with BP fully controlled, despite a > 70% decrease in antihypertensive treatment, while renal function improved at 6 months from 11.5 to 22 ml/min/1.73 m(2). Renal angioplasty confers undisputed benefits in BP control and nephroprotection, and should be offered without delay to patients with renovascular hypertension and/or ischaemic nephropathy.

ObjectivesOur aim is to report four novel α-gal A gene (GLA) mutations resulting in Fabry disease (FD) and provide evidence of pathogenicity of the D313Y mutation regarding which contradictory data have been presented in the literature.Setting and participantsTwenty-five family members of nine unrelated patients with definite FD diagnosis, 10 clinically suspected cases and 18 members of their families were included in this polycentric cohort study.Primary and secondary outcome measuresGenotyping and measurement of lyso-Gb3was performed in all individuals. The α-Gal A activity was measured in all men as well as plasma and urine Gb3concentration in selected cases. Optical and electron microscopy was performed in kidney biopsies of selected patients. All the above were evaluated in parallel with the clinical data of the patients.ResultsFourteen new cases of FD were recognised, four of which were carrying already describedGLAmutations. Four novelGLAmutations, namely c.835C>T, c.280T>A, c.924A>C and c.511G>A, resulting in a classic FD phenotype were identified. Moreover, FD was definitely diagnosed in five patients carrying the D313Y mutation. Eight D313Y carriers were presenting signs of FD despite not fulfilling the criteria of the disease, two had no FD signs and two others were apparently healthy.ConclusionsFour novelGLApathogenic mutations are reported and evidence of pathogenicity of the D313Y mutation is provided. It seems that the D313Y mutation is related to a later-onset milder phenotype than the typical phenotype with normal lysoGb3concentration. Our study underlines the significance of family member genotyping and newborn screening to avoid misdiagnoses and crucial delays in diagnosis and treatment of the disease.

Fever in haemodialysis patients is usually attributed to infection, with less frequent causes including malignancy and autoimmune disorders [1]. Sometimes, fever persists despite empirical treatment, and investigations towards the above mentioned diagnoses fail to reveal the cause. Thus, rarer aetiologies need to be considered, which may appear rather unexpected, especially in patients under prolonged medical follow-up.

Objective:Arterial stiffness and aortic blood pressure (BP) augmentation are significantly increased in hemodialysis patients. Recent studies suggest that the prognostic significance of ambulatory recordings of arterial stiffness is high in hemodialysis. This study examines for the first time the ef

Cardiovascular disease remains the leading cause of increased morbidity and mortality in patients with chronic kidney disease and is attributed to early and accelerated atherosclerosis and arteriosclerosis observed in this patient population. Vascular calcifications, particularly of the media, are commonly found in chronic uremia and are a major contributor to arteriosclerosis and increased arterial stiffness. Epidemiologic data support the correlation of vascular calcification and arterial stiffness to adverse cardiovascular outcomes and mortality. Experimental evidence has shed light on the pathogenetic mechanisms of vascular calcification and arterial stiffness and their relation to impaired bone metabolism and imbalance between promoters and inhibitors of extra-osseous bone formation. However further research is needed to clarify their exact contribution and whether their targeting could significantly affect vascular calcification and arterial stiffening and could improve survival in chronic kidney disease patients.

Background: Insufficient evidenced-based information is available for the treatment of osteoporosis in hemodialysis (HD) patients. Methods: In 102 HD patients, bone mineral density (BMD) was measured twice 16 ± 3 months apart. In the second BMD measurement 66 of them had a femoral neck (FN) T-score 300 pg/ml received cinacalcet, 11 with osteitis fibrosa and iPTH Results: FN and LS BMD decreased significantly in the cinacalcet group, with an annual change of 3.6 and 3.4% before treatment to –4.2% (p = 0.04) and –7.7% (p = 0.02) during treatment, respectively. In the teriparatide group, FN and LS BMD increased, although not significantly, with an annual change of –5.4 and –2.6% before treatment to 2.7 and 4.9% during treatment, respectively. In both the ibandronate and the no treatment groups, BMD change rate remained negative during the whole study. Conclusions: Teriparatide administration improved BMD in HD patients with adynamic bone disease, although these results did not reach statistical significance. In HD patients with osteitis fibrosa, ibandronate did not improve BMD while cinacalcet reduced BMD.

Background Cardiovascular morbidity and mortality remains excessive in patients with chronic kidney disease. The association of vascular changes with regulators of extraosseous calcification in this patient population is still under investigation. The aim of the present study was to investigate the associations of the calcification inhibitor fetuin-A, and the anti-osteoclastic factor osteoprotegerin (OPG) with vascular pathology in chronic hemodialysis patients. Methods In this cross-sectional study including 81 stable chronic hemodialysis patients, we measured carotid-to-femoral pulse wave velocity (cfPWV) with applanation tonometry, reflecting arterial stiffness, and common carotid intima-media thickness (ccIMT), a surrogate of early atherosclerosis, as well as serum levels of fetuin-A and OPG. Co-morbidities, traditional cardiovascular risk factors, inflammatory markers and mineral-bone disease serology parameters were also recorded. Results cfPWV correlated inversely with fetuin-A (r=−0.355, p=0.001) and positively with OPG (r=0.584, p Conclusion In chronic hemodialysis patients both fetuin-A and OPG levels are independently associated with arterial stiffness but not with early atherosclerotic vascular changes.