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Sodium thiosulfate prevents vascular calcifications in uremic rats

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Presentation on theme: "Sodium thiosulfate prevents vascular calcifications in uremic rats"— Presentation transcript:

1 Sodium thiosulfate prevents vascular calcifications in uremic rats
Andreas Pasch, Thomas Schaffner, Uyen Huynh-Do, Brigitte M. Frey, Felix J. Frey, Stefan Farese  Kidney International  Volume 74, Issue 11, Pages (December 2008) DOI: /ki Copyright © 2008 International Society of Nephrology Terms and Conditions

2 Figure 1 Experimental protocol for the adenine treatment of rats. Uremia was induced in 6-week-old male Wistar rats by a 4-week diet containing 0.75% adenine. STS was given intraperitoneally three times a week, as indicated. NUC, nonuremic control animals; UC, uremic control animals; ET, early treatment with STS; LT, late treatment with STS. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

3 Figure 2 Characteristics of the adenine-induced renal failure model. (a) Serum creatinine was higher in all uremic groups at weeks 4 and 10 (***P<0.001) when compared to NUC. At week 4, but not at week 10, ET animals were more uremic than LT and UC animals ($$$P<0.001). (b) Body weight was lower in all uremic groups at weeks 4 and 10 when compared to NUC (***P<0.001). At week 4, but not at week 10, ET and LT animals were lighter than UC animals ($$P<0.01). (c) Progressive polyuria was observed in all uremic groups when compared to NUC animals (***P<0.001). NUC, nonuremic control animals; UC, uremic control animals; ET, early treatment with STS; LT, late treatment with STS. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

4 Figure 3 Representative vascular histology of STS-treated and untreated animals. Micrographs show aortic and coronary media calcifications as assessed by Alizarin red and von Kossa stains. Calcifications are present in uremic animals without treatment, whereas no calcifications are visible in STS-treated uremic animals; *magnification × 4, **magnification × 10. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

5 Figure 4 Calcium and phosphorus content per gram of aortic tissue. Significantly lower amounts of (a) calcium and (b) phosphorus are found in nonuremic controls (NUC) and STS-treated uremic animals (ET, LT) when compared to uremic, untreated controls (UCs). Calcium and phosphorus contents were not different between NUC, ET, and LT rats. **P<0.01 and ***P<0.001 when compared to UC. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

6 Figure 5 Calcium content per gram of (a) heart and (b) kidney tissue. Heart calcium content was reduced in all STS-treated groups when compared to untreated uremic animals. Also, kidney calcium content was higher in untreated uremic controls when compared to uremic STS-treated rats. Calcium content in heart and kidney tissues was not different in NUC, ET, and LT rats. *P<0.05, **P<0.01, ***P<0.001 when compared to UC. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

7 Figure 6 Calciuria in STS-treated and untreated rats. Urine was collected in metabolic cages at the end of the experiment. STS-treated rats excreted more calcium than untreated uremic rats (**P=0.01 and ***P<0.001 for NUC, ET, and LT when compared to UC). NUC, STS-treated nonuremic control animals; UC, uremic control animals; ET, early treatment with STS; LT, late treatment with STS. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

8 Figure 7 Responses to STS application in rats. Blood was taken from anesthetized uremic 5/6 nephrectomized rats before and after STS application at the time points indicated. At 15min after STS dosing, the ionized calcium concentration was diminished (*P<0.05) when compared to baseline and rose again after 30min when compared to the lowest concentration at 15min (§P<0.05 and §§P<0.01), but not when compared with baseline values. The other significance values in Figures 7 a–f are given in comparison to baseline (0-value) concentrations: *P<0.05, **P<0.01, ***P<0.001. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

9 Figure 8 Changes in urinary calcium concentrations (a) and pH after STS application (b). Urine was collected from anesthetized uremic 5/6 nephrectomized rats before and post STS application at the time points indicated. Significances are given in comparison to baseline (0-value): *P<0.05, **P<0.01. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

10 Figure 9 Impact of STS on ionized calcium and pH in vitro. Human blood from healthy volunteers (n=7) was incubated with increasing concentrations of STS. Ionized calcium was measured at 37°C under anerobic conditions whereas pCO2 and HCO3– were kept stable. The double arrow indicates the range of STS concentrations that were measured after intraperitoneal STS injection of 0.4g/kg in rats. Only small (nonsignificant) pH changes occurred in this concentration range. Although pH declines at higher STS concentrations, ionized calcium progressively decreases. Significances are expressed in relation to ionized calcium measured in the absence of STS (0mmol/l): *P<0.05, ***P< Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

11 Figure 10 Bone morphology of STS-treated and untreated uremic and nonuremic animals. Microcomputed tomography slices of rat femurs (a, c) with and (b, d) without STS treatment. Nonuremic rats had normal bone architecture, whereas a reduced mineralization and cystic transformations were present in the uremic animals. These findings were independent of STS treatment. Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions

12 Figure 11 Functional studies of bone integrity. (a) Stiffness and (b) fracture stability of rat femurs were assessed by applying standardized forces to bones. Stiffness and fracture stability of nonuremic bone were invariably higher when compared to uremic bones ($$$a and b, P<0.001). Stiffness did not differ between STS-treated and untreated animals (a). Fracture stability was significantly lower in STS-treated than untreated bone from nonuremic rats (b, left bars, **P<0.01). The same applied to uremic animals, although the difference did not reach statistical significance (b, right bars, #P=0.06). Kidney International  , DOI: ( /ki ) Copyright © 2008 International Society of Nephrology Terms and Conditions


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