Search

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.

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.

Background Klotho is a transmembrane protein acting as a co-receptor for FGF-23 and thus exerts clinical actions on mineral metabolism. The association of secreted Klotho with outcomes in CKD patients is unclear. This study examined the relation between plasma Klotho and cardiovascular events in dialysis patients, accounting for common and CKD-MBD related risk factors, arterial stiffness and atherosclerotic burden. Methods Seventy-nine chronic hemodialysis patients were observed for a median follow-up of 5.5 years. Klotho levels as well as carotid–femoral pulse wave velocity (cfPWV) and common carotid intima-media thickness (ccIMT) measurements were performed at baseline. The primary end-point was first occurrence of all-cause death, non-fatal myocardial infarction or non-fatal stroke. Secondary end-points were: (i) all-cause mortality; (ii) cardiovascular mortality; (iii) a combination of cardiovascular death, non-fatal MI, non-fatal stroke, resuscitation after cardiac arrest, coronary revascularization, heart failure hospitalization and atrial fibrillation. Results Cumulative freedom from the primary endpoint was 31% for the low-Klotho group (≤745 pg/ml) and 53% for the high-Klotho group (logrank p = 0.017); HR: 2.137, 95%CI 1.124–4.065. Cumulative survival was insignificantly lower (44% vs 56%, p = 0.107), but cumulative cardiovascular survival (63% vs 88%, p = 0.029) and cumulative freedom from the cardiovascular composite outcome (18% vs 45%, p = 0.009) were significantly lower in the low-Klotho group. In modelled Cox-regression analysis the association of low Klotho with the primary endpoint remained significant after stepwise adjustment for cFGF3, PTH, Ca x P product, established risk factors (age, dialysis vintage, diabetes, hypertension, smoking, history of cardiovascular disease) as well as cfPWV and ccIMT [Model 6: HR:2.759, 95%CI 1.223–6.224, p = 0.014]. Conclusions Low Klotho is associated with cardiovascular events in hemodialysis patients, independently from factors associated with mineral-bone disease, common risk factors and intermediate outcomes, such as cfPWV and ccIMT.

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.

Nephritis represents a frequent, severe complication of systemic lupus erythematosus. Autoantibodies appear to be fundamental in the pathogenesis of lupus nephritis. Several hypotheses are currently experimentally tested to further elucidate the direct induction of inflammation through interaction of the pathological autoantibodies with intrinsic glomerular components and the triggering of a complement-driven autoinflammatory cascade. B-cells have, in the last decade, emerged as a promising new therapeutic target, as biological treatments successfully attempting B-cell depletion, inhibition of B-cell proliferation and differentiation, or modulation of B-cell function have become bioengineered. Clinical trials have so far proved controversial regarding the efficacy of these new agents. Thus, despite the short and long-term side effects associated with immunosuppressive treatment alternative emerging treatments are still regarded “rescue” regimens in refractory patients. In an effort to accurately evaluate the potential of these therapies in lupus nephritis, several issues have been raised mainly in terms of patient selection criteria and trial duration. This review aims to expand on the proposed pathophysiologic mechanisms implicating the B-cell pathway in the pathogenesis of lupus nephritis and summarize current knowledge obtained from clinical trials introducing these biologics in its treatment. Finally, it will elaborate on potential applications of currently available biologic agents and forthcoming treatment options.

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.