Increased bone strontium levels in hemodialysis patients with osteomalacia

Increased bone strontium levels in hemodialysis patients with osteomalacia.BackgroundIn this study, we report on the association between increased bone strontium levels and the presence of osteomalacia in end-stage renal failure patients treated by hemodialysis.MethodsWe performed a histologic examination and determined the strontium content and strontium/calcium ratios in bone biopsies of 100 hemodialysis patients recruited from various centers all over the world. Aside from the bone strontium concentration, the bone aluminum content was assessed. The bone zinc concentration, a nonrelevant element for bone toxicity, was also measured.ResultsBone strontium levels and bone strontium/calcium ratios were increased in subjects with osteomalacia when compared with those with the other types of renal osteodystrophy. Bone strontium and bone calcium levels correlated with each other. The slope of the linear regression curve correlating these parameters was much steeper in the osteomalacic group (Y = 2.22X - 120) as compared with the other types of renal osteodystrophy (Y = 0.52X - 5.7). Within the group of patients with osteomalacia, bone strontium levels also significantly correlated with the bone aluminum content (r = 0.72, P = 0.018). No such correlation was found for the other types of renal osteodystrophy. The bone zinc concentration of subjects with normal renal function did not differ significantly from the values noted for the various types of renal osteodystrophy taken as separate groups, nor could increased bone zinc concentrations be associated with a particular bone lesion.ConclusionsOur data demonstrate an association between osteomalacia and increased bone strontium concentrations in dialysis patients. Further studies are warranted to establish whether strontium plays either a primary, secondary, or contributive role in the development of the latter type of renal osteodystrophy

FCGG Renal Biopsy Network: first epidemiological report on pediatric renal disease in Flanders

FCGG Renal Biopsy Network: first epidemiological report on pediatric renal diseases Sevasti Karamaria1, Johan De Meester2, Amélie Dendooven3, Elena Levtchenko4, Noel Knops4, Koen Van Hoeck5, Dominique Trouet5, Reiner Mauel6, Ben Sprangers7, Wim Laurens8, Johan Vande Walle1, on behalf of the FCGG – NBVN working group 1 Department of Pediatrics, UZ Gent, Ghent; 2NBVN, Antwerp; 3Pathology Department, UZ Gent, Ghent; 4Department of Pediatrics, UZ Leuven, Leuven; 5Departement of Pediatrics, UZ Antwerpen, Antwerp; 6Department of Pediatrics, UZ Brussel, Brussels; 7Department of Nephrology, UZ Leuven, Leuven; 8Department of Nephrology, AZ Nikolaas, Sint-Niklaas. Objective: In 2016, a regional renal biopsy network was founded as a collaboration between renal pathologists and nephrologists in order to standardize diagnosis and therapy. Uniform renal biopsy request and renal biopsy report forms were introduced, together with a new comprehensive list of renal pathology diagnoses for coding. The 2017-2018 epidemiological data of the pediatric patients (age= 0-17 years) are presented. Methods: Following informed consent and in compliance with GDPR, data registration consists of basic patient and categorical renal data, semi-structured medical information of renal histopathology and the clinical renal disease. Results: In 2017-2018, 92 renal biopsies were reported in pediatric patients or 3.6 per 100,000 pediatric inhabitants per year. Three clinical patterns were equally represented: only proteinuria >1g/day; only hematuria; and combination of proteinuria and hematuria. Acute or chronic renal failure were rare. In the youngest age group (0-5 years; N=26) minimal change disease predominated, followed by Henoch-Schönlein nephritis. The middle age group (6-11 years; N=32) mainly presented with disease characterized by hematuria: IgA nephropathy, Henoch-Schönlein nephritis and Alport’s disease. A more diverse renal disease spectrum was present in the highest age group (12-18 years; N=34): IgA nephropathy, different forms of proliferative glomerulonephritis and of nephrotic syndrome of childhood. Patients with a Caucasian descent presented with IgA nephropathy, while a nephrotic syndrome was more common in those without a Caucasian descent. Alport’s disease was particularly diagnosed in female patients, IgA nephropathy in male patients, and the gender distribution was equal in minimal change disease. Conclusion: The FCGG network provides an better cross-talk between renal pathologists and nephrologists. For the first time, reliable estimates of pediatric renal diseases based on histology are available. Genetic analyses are not yet included. Efforts to coordinate clinical care of pediatric renal diseases are ongoing

Acute Exercise-Induced Response of Monocyte Subtypes in Chronic Heart and Renal Failure

Purpose. Monocytes (Mon1-2-3) play a substantial role in low-grade inflammation associated with high cardiovascular morbidity and mortality of patients with chronic kidney disease (CKD) and chronic heart failure (CHF). The effect of an acute exercise bout on monocyte subsets in the setting of systemic inflammation is currently unknown. This study aims (1) to evaluate baseline distribution of monocyte subsets in CHF and CKD versus healthy subjects (HS) and (2) to evaluate the effect of an acute exercise bout. Exercise-induced IL-6 and MCP-1 release are related to the Mon1-2-3 response. Methods. Twenty CHF patients, 20 CKD patients, and 15 HS were included. Before and after a maximal cardiopulmonary exercise test, monocyte subsets were quantified by flow cytometry: CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2− (Mon3). Serum levels of IL-6 and MCP-1 were determined by ELISA. Results. Baseline distribution of Mon1-2-3 was comparable between the 3 groups. Following acute exercise, %Mon2 and %Mon3 increased significantly at the expense of a decrease in %Mon1 in HS and in CKD. This response was significantly attenuated in CHF (P<0.05). In HS only, MCP-1 levels increased following exercise; IL-6 levels were unchanged. Circulatory power was a strong and independent predictor of the changes in Mon1 (β=-0.461, P<0.001) and Mon3 (β=0.449, P<0.001); and baseline LVEF of the change in Mon2 (β=0.441, P<0.001). Conclusion. The response of monocytes to acute exercise is characterized by an increase in proangiogenic and proinflammatory Mon2 and Mon3 at the expense of phagocytic Mon1. This exercise-induced monocyte subset response is mainly driven by hemodynamic changes and not by preexistent low-grade inflammation

Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia

Relapse is a major problem in acute myeloid leukemia (AML) and adversely impacts survival. In this phase II study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) mRNA as post-remission treatment in 30 AML patients at very high risk of relapse. There was a demonstrable anti-leukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which are sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in non-responders (53.8% vs. 25.0%; P=0.01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25% and the 5-year relapse-free survival was higher in responders than in non-responders (50% vs. 7.7%; P65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared to 51.7% and 18% in the Swedish Acute Leukemia Registry (SALR). Long-term clinical response was correlated with increased circulating frequencies of poly-epitope WT1-specific CD8+ T-cells. Long-term OS was correlated with interferon-γ+ and tumor necrosis factor-α+ WT1-specific responses in delayed type hypersensitivity-infiltrating CD8+ T-lymphocytes. In conclusion, vaccination of AML patients with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8+ T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224

Oxidative Injury To Erythrocytes, Cell Rigidity and Splenic Hemolysis in Hemodialyzed Patients Before and During Erythropoietin Treatment

The oxidative injury to erythrocytes, red blood cell (RBC) rigidity and splenic hemolysis was assayed in 17 chronically hemodialyzed patients before and during recombinant erythropoietin (EPO) treatment. When a stable hematocrit between 30 and 35% had been established for at least 4 months, a statistically significant increase in RBC volume, hemoglobin concentration, hematocrit, reticulocyte count, and several RBC enzymes (2,3-diphosphoglycerate, glucose 6-phosphate dehydrogenase, pyruvate kinase, hexokinase) was noted. This indicated significant RBC rejuvenation under the influence of EPO. However, no significant improvement in the RBC oxidative sensitivity, RBC deformability, splenic RBC volume, slow mixing splenic RBC volume, and the intrasplenic RBC transit time could be disclosed. These data confirm the existence of an extraerythrocytic factor in uremic plasma, which is partly responsible for a reduced RBC life span in hemodialysis patients despite EPO treatment

Vascular effects of exercise training in CKD : current evidence and pathophysiological mechanisms

Cardiovascular disease remains the main cause of morbidity and mortality in patients with CKD, an observation that cannot be explained by the coexistence of traditional risk factors alone. Recently, other mechanisms, such as alterations in nitric oxide bioavailability, impaired endothelial repair mechanisms, inflammation, and oxidative stress (all characteristic in CKD), have gained much attention as mediators for the increased cardiovascular risk. Regular physical training is a valuable nonpharmacological intervention for primary and secondary prevention of cardiovascular disease. Likewise, the benefits of exercise training on exercise capacity and quality of life are increasingly recognized in patients with CKD. Furthermore, exercise training could also influence potential reversible mechanisms involved in atherosclerosis and arteriosclerosis. After discussing briefly the general concepts of vascular disease in CKD, this review provides an overview of the current evidence for the effects of exercise training at both clinical and preclinical levels. It concludes with some practical considerations on exercise training in this specific patient group

Acute Exercise-Induced Response of Monocyte Subtypes in Chronic Heart and Renal Failure

Purpose. Monocytes (Mon1-2-3) play a substantial role in low-grade inflammation associated with high cardiovascular morbidity and mortality of patients with chronic kidney disease (CKD) and chronic heart failure (CHF). The effect of an acute exercise bout on monocyte subsets in the setting of systemic inflammation is currently unknown. This study aims (1) to evaluate baseline distribution of monocyte subsets in CHF and CKD versus healthy subjects (HS) and (2) to evaluate the effect of an acute exercise bout. Exercise-induced IL-6 and MCP-1 release are related to the Mon1-2-3 response. Methods. Twenty CHF patients, 20 CKD patients, and 15 HS were included. Before and after a maximal cardiopulmonary exercise test, monocyte subsets were quantified by flow cytometry: CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2− (Mon3). Serum levels of IL-6 and MCP-1 were determined by ELISA. Results. Baseline distribution of Mon1-2-3 was comparable between the 3 groups. Following acute exercise, %Mon2 and %Mon3 increased significantly at the expense of a decrease in %Mon1 in HS and in CKD. This response was significantly attenuated in CHF (P<0.05). In HS only, MCP-1 levels increased following exercise; IL-6 levels were unchanged. Circulatory power was a strong and independent predictor of the changes in Mon1 (β=-0.461, P<0.001) and Mon3 (β=0.449, P<0.001); and baseline LVEF of the change in Mon2 (β=0.441, P<0.001). Conclusion. The response of monocytes to acute exercise is characterized by an increase in proangiogenic and proinflammatory Mon2 and Mon3 at the expense of phagocytic Mon1. This exercise-induced monocyte subset response is mainly driven by hemodynamic changes and not by preexistent low-grade inflammation