23 research outputs found
High ankle-brachial index predicts cardiovascular events and mortality in hemodialysis patients with severe secondary hyperparathyroidism
No full textAbstract Introduction: Vascular calcification related to severe secondary hyperparathyroidism (SHPT) is an important cause of cardiovascular and bone complications, leading to high morbidity and mortality in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). The present study aimed to analyze whether ankle-brachial index (ABI), a non-invasive diagnostic tool, is able to predict cardiovascular outcomes in this population. Methods: We selected 88 adult patients on HD for at least 6 months, with serum iPTH>1,000pg/mL. We collected clinical data, biochemical and hormonal parameters, and ABI (sonar-Doppler). Calcification was assessed by lateral radiography of the abdomen and by simple vascular calcification score (SVCS). This cohort was monitored prospectively between 2012 and 2019 for cardiovascular outcomes (death, myocardial infarction (MI), stroke, and calciphylaxis) to estimate the accuracy of ABI in this setting. Results: The baseline values were: iPTH: 1770±689pg/mL, P: 5.8±1.2 mg/dL, corrected Ca: 9.7±0.8mg/dL, 25(OH)vit D: 25.1±10.9ng/mL. Sixty-five percent of patients had ABI>1.3 (ranging from 0.6 to 3.2); 66% had SVCS≥3, and 45% aortic calcification (Kauppila≥8). The prospective evaluation (51.6±24.0 months), provided the following cardiovascular outcomes: 11% of deaths, 17% of nonfatal MI, one stroke, and 3% of calciphylaxis. After adjustments, patients with ABI≥1.6 had 8.9-fold higher risk of cardiovascular events (p=0.035), and ABI≥1.8 had 12.2-fold higher risk of cardiovascular mortality (p=0.019). Conclusion: The presence of vascular calcifications and arterial stiffness was highly prevalent in our population. We suggest that ABI, a simple and cost-effective diagnostic tool, could be used at an outpatient basis to predict cardiovascular events in patients with severe SHPT undergoing HD.</div
One-Year Conservative Care Using Sodium Bicarbonate Supplementation Is Associated with a Decrease in Electronegative LDL in Chronic Kidney Disease Patients: A Pilot Study
No full text<b><i>Background:</i></b> Chronic kidney disease (CKD) patients develop metabolic acidosis when approaching stages 3 and 4, a period in which accelerated atherogenesis may ensue. Studies in vitro show that low pH may increase low-density lipoprotein (LDL) oxidation, suggesting a role for chronic metabolic acidosis in atherosclerosis. The present study attempted to evaluate the effects of conservative care using oral sodium bicarbonate (NaHCO<sub>3</sub>) supplementation on the electronegative LDL [LDL(-)], a minimally oxidized LDL, plasma levels in CKD patients. <b><i>Methods:</i></b> Thirty-one CKD patients were followed by a multidisciplinary team during 15 months of care in which 1.0 mmol/kg/day oral NaHCO<sub>3</sub> supplementation was first given in the third month. Blood samples were collected 3 months before the initiation of oral NaHCO<sub>3</sub> supplementation (T1), at the time of the beginning of supplementation (T2), and thereafter, each 4 months (T3, T4 and T5) until month 15 of care. Blood parameters and LDL(-) were measured from these collections. <b><i>Results:</i></b> After 12 months of conservative care, creatinine clearance (MDRD) was kept stable, and serum bicarbonate (HCO<sub>3</sub><sup>-</sup>) increased from 20.5 ± 2.9 to 22.6 ± 1.1 m<smlcap>M</smlcap> (<i>p</i> < 0.003). LDL(-) plasma levels declined from 4.5 ± 3.3 to 2.1 ± 0.9 U/L (<i>p</i> < 0.007) after reaching mean serum HCO<sub>3</sub><sup>-</sup> levels of 22.6 ± 1.1 m<smlcap>M</smlcap>. <b><i>Conclusions:</i></b> Conservative care using oral NaHCO<sub>3</sub> supplementation was able to stabilize renal function and decrease serum levels of LDL(-), a modified proatherogenic lipoprotein, only when mean serum HCO<sub>3</sub><sup>-</sup> levels approached 22 m<smlcap>M</smlcap>. This study constitutes evidence that alkali therapy, in addition to its beneficial effect on renal disease progression, might serve as a preventive strategy to attenuate atherogenesis in CKD patients.</jats:p
Nutritional strategies to modulate inflammation and oxidative stress pathways via activation of the master antioxidant switch Nrf2
No full textCharacterization of the chimeric immune system.
No full text<p>Blood, bone marrow and splenic digests were analysed by flow cytometry to define the leukocyte populations (n = 26 mice). Treatment groups were matched by degree of peripheral blood chimerism prior to IgG injection. hMono = human monocytes. There was no significant difference in degree of chimerism or human granulocyte reconstitution between the experimental groups.</p
Anti-PR3 antibodies induce capillaritis with leukocytes of mouse and human origin.
No full text<p>(A) Photomicrographs of explanted lungs from mice treated with disease control IgG (n = 8) or from patients with anti-PR3 ANCA (n = 18). Mice treated with anti-PR3 ANCA displayed petechiae over the surface of the lung. (B) H&E stained low and high power images of lungs from chimera mice injected with anti-PR3 antibodies 6 days previously. Note hemorrhage, inflammation, thickening of alveolar walls, enlarged, highly vacuolated alveolar macrophages and prominent recruitment of neutrophils (arrows) within the alveolar walls. These features are consistent with capillaritis. By comparison chimera mice treated with control IgG showed normal lung architecture. (C) Immunostaining of lung tissue to assess the degree of leukocyte infiltration. Note that in mice that received anti-PR3 ANCA IgG there was significant recruitment of leukocytes to the peribronchial areas (thin arrows) and also the alveolar areas (fat arrows). In addition many alveoli in mice treated with anti-PR3 antibodies had apoptotic debris that was partially ingested by alveolar macrophages (arrowheads) (bar = 50 µm). (D) Blinded assessment of human and mouse leukocyte recruitment to the lungs of treated animals (** <i>P</i><0.01. median ± IQ ± max/min values).</p
Anti-PR3 antibodies cause kidney disease.
No full text<p>(A–C) PAS stained images of glomeruli from chimera mice 6 days after injection with anti-PR3 (n = 18, A, 400×; C, 600×) or control IgG (n = 8, B, 600×). Note extra-capillary proliferation and peri-glomerular inflammation (arrowhead) (A), and mesangiolysis (C, arrow) in anti-PR3 treated mice. (D–F) H & E stained sections of kidney from chimera mice treated with anti-PR3 (D, 40×) or disease control (E, 40×) IgG. There are regions of tubulointerstitial injury, with red cell cast formation (arrow). (F) Demonstrates intense peri-glomerular inflammation in an animal treated with anti-PR3 IgG (arrowhead, 400×). By comparison mice treated with disease control IgG showed minimal glomerular or tubulointerstitial changes. (G) Fractions of glomeruli affected in anti-PR3 (n = 18) and control IgG (n = 8) treated animals (Error bars depict SEM; ***<i>p</i> = 0.001) (H). Degree of tubulointerstitial disease in mice treated with anti-PR3 antibodies and control antibodies (*<i>P</i><0.05, median ± IQ ± max/min values). (Bars = 50 µm).</p
HR-pQCT detects alterations in bone microstructure in men with CKD stages 3 and 4, which are influenced by hormonal changes and body composition
No full textEffect of LPS and TNFα on neutrophil recruitment into the mouse circulation.
No full text<p>WT FVB mice were treated with TNFα (1 µg/kg i.v., n = 3) or LPS (1500 EU/g i.p., n = 3) and the degree of PMN mobilisation was quantified by staining peripheral blood for LY6G.</p><p>*p<0.05 compared to pre-treatment value. N = 3/group.</p
Anti-PR3 antibodies induce infiltration of kidneys with leukocytes of murine and human origin.
No full text<p>Kidney sections were incubated with anti-mCD45 (red) and anti-hCD45 (green) antibodies and images were captured by fluorescence microscopy (T = tubule). Occasional (<5%) glomeruli of anti-PR3 treated mice displayed intense extracapillary leukocyte infiltration (A) in the shape of crescents (arrows). Most glomeruli in animals treated with anti-PR3 antibodies (n = 18) had evidence of intraglomerular (B,G) and peri-glomerular (C,G) leukocyte infiltration. These were comprised mostly of mCD45+ cells, although some hCD45 leukocytes were also present (arrowheads). In addition, there was a significant increase in peri-vascular leukocyte (mCD45+ and hCD45+) infiltration in anti-PR3 treated mice (D,G [per arteriolar section (art.sec.)]). Sections were also stained for deposition of IgG [red] (E,G) and C3 [green] (F,G). IgG was detectable within periglomerular cells, but there was minimal deposition within the glomeruli. Mouse C3 was weakly deposited in glomeruli but was no different between control group (n = 8) and anti-PR3 group (n = 18). Note mouse C3 can be detected normally binding avidly to tubular basement membranes. (Marker = 10 µm) (*<i>P</i><0.05, **<i>P</i><0.01. median ± IQ ± max/min values). (H) Kidney sections from anti-PR3 and control treated animals were incubated with anti-PR3 positive ANCA IgG. In the peritubular capillaries of chimera mice that received anti-PR3 hIgG occasional leukocytes detected by anti-hPR3 hIgG could be detected. No positively stained human neutrophils were seen in glomeruli.</p
Characterization of chimerism in NOD-<i>scid</i>-<i>IL2Rγ<sup>−/−</sup></i> mice.
No full text<p>(A–D) Flow cytometric analysis of leukocytes from tail bleeds six weeks after administration of HSCs (n = 26 mice). (A) Plots showing mouse leukocytes labelled with anti-mouse CD45 antibodies. Compared with control wild-type mouse blood, chimeras have populations of mCD45 negative leukocytes that show SSC characteristics of granulocytes (High), monocytes (Int) and lymphocytes (low). (B) Chimera blood leukocytes express human CD45 and many of these express CD11b. hCD45+,CD11b+ leukocytes predominantly express hCD15 and hCD66b compared with hCD45+,CD11b− leukocytes shown in histograms. (C) A proportion of hCD45+ leukocytes express CD19. (D) Some hCD45 leukocytes are CD14<sup>high</sup> and some are CD16+,CD14<sup>low</sup>. (E) In chimera bone marrow there are CD11b+ leukocytes which do not express mCD45 and among hCD45+ leukocytes a proportion express CD14 and a proportion express CD66b. (F) In chimera spleen there are CD11b+ leukocytes which express hCD45 and among hCD45+ leukocytes many express both CD14 and CD16. (G) Bone marrow spreads from wild type or chimera mice, labelled with anti-hMPO or anti-hPR3 IgG antibodies (red) purified from patients with vasculitis. Note that chimera bone marrow demonstrates anti-hMPO or anti-hPR3 antibody positive leukocytes with characteristic human neutrophil nuclear morphology. Wild type mouse bone marrow shows no cells positive for these antigens indicating that the anti-human antibodies do not cross react with mouse neutrophils.</p
