Supplemented Very Low Protein Diet (sVLPD) in Patients with Advanced Chronic Renal Failure: Clinical and Economic Benefits.

The supplemented very low-protein diet (sVLPD) has proven effective in slowing the progression of stage 5 chronic renal failure and postponing the start of the dialysis treatment. However, sVLPD could expose the patient to the risk of malnutrition. This diet is also difficult to implement due to the required intake of large number of keto-analogue/amino acid tablets. In our Center, the Department of Nephrology and Dialysis of Azienda Sanitaria Territoriale n 1, Pesaro-Urbino, of Italy, respecting the guidelines of normal clinical practice, we prescribed sVLPD (0.3 g/prot/day) supplemented with only essential amino acids without the use of ketoanalogues in stage 5 patients and verified its efficacy, safety and clinical and economic effects. Over the 24 months period of observation the progression of chronic kidney disease (CKD) slowed down (mean eGFR 11.6 ± 3.3 vs. 9.3 ± 2.7 mL/min/1.73 m2, p < 0.001) and the start of the dialysis treatment (adjusted HR = 0.361, CI 0.200-0.650, p = 0.001) was delayed without evidence of malnutrition, in compliant vs. non-compliant patients. This led to a substantial cost reduction for the National Health System. This non-interventional longitudinal observational study is part of standard clinical practice and suggests that VLPD supplemented with essential amino acids could be extensively used to reduce the incidence of dialysis treatments, with a favorable economic impact on the NHS.

[SARS CoV-2 related disease features in a population of chronic hemodialysis patients].

Patients on chronic dialysis have an increased risk for SARS CoV-2 virus disease and its complications because of multiple comorbidities and alterations in the immune response caused by renal disease. In this retrospective observational study we describe the clinical features and the evolution of SARS CoV-2-related disease in 19 patients of our Pesaro and Fano facilities, where incidence and mortality of the epidemic were among the highest in Italy. A total of 176 patients were undergoing chronic treatment, 153 hemodialysis and 23 peritoneal dialysis. The incidence of infection was 10,8%, with 84% needing hospitalization and mortality amounting to 53%. The most frequent onset symptom was fever (84,2%) and the most used therapy was an association of low molecular weight heparin and hydroxychloroquine (57,9%). Comparing the deceased and survivor populations we noticed significant differences in age and presence of cardiopathy for what concerns anamnestic data and in fatigue and dyspnea in terms of clinical presentation. LDH and CPK resulted highest among deceased patients, while the use of enoxaparin was more frequent in survivors. By observing contagions over time, we also noticed that most of the cases, and the ones with worse clinical condition and outcome, all occurred in the early stage of the epidemic and in particular within the first 20 days from the implementation and codification of the measures to prevent its spread, the only modifiable factor that had an unmistakable effect on the evolution of events.

Removal of uraemic plasma factor(s) using different dialysis modalities reduces phosphatidylserine exposure in red blood cells.

BACKGROUND: Solute(s) retained during uraemia cause increased exposure of aminophospholipid phosphatidylserine (PS) on the outer surface of erythrocyte membranes, and this phenomenon may be involved in the pathophysiology of uraemia by promoting abnormal erythrocyte interactions. METHODS: We examined in a prospective randomized cross-over fashion the ability of various dialysis modalities to remove the circulating uraemic factor(s) causing increased PS externalization in red cells. Each patient was treated with haemodialysis (HD) and with on-line haemodiafiltration (HDF) using standard high-flux polysulphone membranes or with the new polisulphone-based Helixone membrane to compare the effects of dialysis technique and membrane type on PS exposure. Removal of PS was assessed indirectly by measuring PS-expressing normal erythrocytes exposed to uraemic plasma or to ultrafiltrate obtained at various time points during the extracorporeal session. RESULTS: Removal of the uraemic plasma factor(s) causing PS exposure was demonstrated by the reduced ability of uraemic plasma at the end of dialysis to induce PS exposure in normal erythrocytes, and by the capacity of ultrafiltrate from the dialysate side of the dialyzer membrane to markedly increase PS-positive red cells. However, the degree of removal varied according to the dialyzer type and to dialysis technique. Removal was greater for on-line HDF using the Helixone membrane, intermediate and comparable with HD with Helixone and with on-line HDF using standard polysulphone, and lower for HD using polysulphone membrane. The putative uraemic compound causing PS exposure seems to be highly lipophilic, somehow associated with plasma proteins, and apparently having a molecular weight between 10 and 10.8 kDa. CONCLUSIONS: Uraemia is associated with retention of compound(s) that are lipophilic, possibly protein-bound and which cause an abnormal exposure of PS in erythrocytes. Our findings, that such compound(s) can be removed during dialysis and at higher rates with convection techniques, indicate a potential benefit for uraemic patients. The present results also seem to confirm the marked ability of high-flux Helixone membranes to eliminate high molecular weight solutes.

Enhanced adherence of human uremic erythrocytes to vascular endothelium: role of phosphatidylserine exposure.

BACKGROUND: The exposure of phosphatidylserine (PS) on the outer leaflet of erythrocyte membrane may have several pathophysiological consequences including increased erythrocyte adherence to endothelial cells, a finding that seems relevant in pathologies with reported vascular injury. METHODS: Because PS externalization increases in erythrocytes from patients suffering from chronic uremia, which is frequently associated with vascular damage, the adherence of uremic erythrocytes to human umbilical vein endothelial cell (HUVEC) monolayers and the role of PS exposure on such cell-cell interaction were studied. RESULTS: The number of uremic erythrocytes adhering to HUVEC was markedly greater than with normal erythrocytes and significantly correlated (r = 0.88) with the percentage of PS-exposing erythrocytes in the population. Adhesion to the monolayers was significantly decreased when uremic erythrocytes were preincubated with either annexin V or PS-containing liposomes, and was strongly greater for PS-positive than PS-negative fluorescence-activated cell sorter (FACS)-sorted uremic erythrocytes. Binding occurred preferentially in the gaps of HUVEC monolayers and was enhanced by matrix exposure. Uremic erythrocytes adhered to immobilized thrombospondin, and binding to endothelial cells was significantly reduced when monolayers were incubated with antibodies to thrombospondin. CONCLUSIONS: These findings suggest that PS externalization may promote increased uremic erythrocyte adhesion to endothelium, possibly via a direct interaction with matrix thrombospondin.