Aortic calcification in vehicle versus 185 mg/kg CaMg treated chronic renal failure (CRF) rats.

<p>*: p<0.05 vs. CRF + vehicle.</p

Urine biochemistry over time of 5/6^th nephrectomized rats receiving normal phosphorus (NP) or high phosphorus (HP) diet, in combination with vehicle (Veh), 185 or 375 mg/kg CaMg.

<p>*: p<0.05 vs NP, same dose.</p><p>°: p<0.05 vs week −4, same diet and dose.</p><p>Urine biochemistry over time of 5/6^th nephrectomized rats receiving normal phosphorus (NP) or high phosphorus (HP) diet, in combination with vehicle (Veh), 185 or 375 mg/kg CaMg.</p

Calcium and magnesium content in the tibia of 5/6^th nephrectomized rats on a normal (NP) or high phosphorus (HP) diet treated with either vehicle (veh), 185 or 375 mg/kg/day CaMg.

<p>Calcium and magnesium content in the tibia of 5/6^th nephrectomized rats on a normal (NP) or high phosphorus (HP) diet treated with either vehicle (veh), 185 or 375 mg/kg/day CaMg.</p

Static and dynamic bone parameters of 5/6^th nephrectomized rats on a normal (NP) or high phosphorus (HP) diet treated with either vehicle (veh), 185 or 375 mg/kg/day CaMg.

<p>*: p<0.05 vs. NP, same dose.</p

Setup of the study addressing the effect of calcium acetate/magnesium carbonate (CaMg) on bone.

<p>The three groups presented in the clear bars received a normal phosphorus diet; those presented in the hatched bars received a high phoshorus diet. Nx: 5/6^th nephrectomy.</p

Urinary phosphorus levels in 5/6^th nephrectomized rats on a normal (NP) or high phosphorus (HP) diet treated with either vehicle (veh), 185 or 375 mg/kg/day CaMg.

<p>*: p<0.05 vs NP, same dose; #: p<0.05 vs vehicle, same diet; °: p<0.05 vs week −4, same diet and dose.</p

Serum biochemistry of vehicle versus 185 mg/kg CaMg treated adenine-induced CRF rats.

<p>*: p<0.05 vs. vehicle treated CRF rats, same time point.</p><p>°: p<0.05 vs. week 0, same treatment group.</p><p>Serum biochemistry of vehicle versus 185 mg/kg CaMg treated adenine-induced CRF rats.</p

Pharmacokinetic parameters after single intravenous bolus administration of SNF472 into rats.

<p>Pharmacokinetic parameters after single intravenous bolus administration of SNF472 into rats.</p

Preventive effects of SNF472 on cardiovascular calcification induced by vitamin D in rats. Effect on serum calcium and phosphorus levels in rats and <i>in vitro</i> binding studies.

<p>Calcium levels in aorta (A) and heart (B) and calcium (C) and phosphorus (D) levels in serum after calcification induction by 5 consecutive daily oral administrations of 75 kIU/kg vitamin D₃ in control and treated animals. SNF472 d.: 1 mg/kg daily i.v. administration; SNF472 e.o.d.: 1 mg/kg every other day i.v. administration. (E) Binding kinetics of SNF472 on hydroxyapatite (HAP) assessed after incubation with 130 mg HAP in the presence of 5000 ng/ml SNF472 at 37 °C, pH 7.4. (F) Release kinetics of SNF472 from HAP. A solution of 5000 ng/ml SNF472 was incubated for 2 h at 37 °C in the presence of 130 mg HAP. HAP was recovered by filtration and incubated for up to 7 days in fresh 0.05 M Tris buffer, pH 7.40. (A, B, C, D) Boxplot representation of the results showing the median (horizontal black bar), Q1 (lower box), Q3 (upper box) and lower and upper limit. (E, F) Results represent mean ± SD. Statistical analysis: One-way ANOVA. (*) indicates significant differences vs. Sham group; (#) indicates significant differences vs. corresponding vehicle, p < 0.05. In vivo study (N = 5). In vitro study (N = 3).</p

Biochemical parameters and SNF472 PK levels in adenine-induced uremic rats.

<p>(A) Urea, (B) creatinine, (C) calcium and (D) phosphorus levels and (E) alkaline phosphatase activity in serum of adenine-induced uremic rats treated with vehicle or SNF472 via 4 h intravenous infusion. (F) Phytate levels at the end of infusion (4 h) on days 0, 9 and 18 in the SNF472-treated group (phytate levels in control animals lower than the lower limit of quantification). (A, B, C, D, E) Boxplot representation of the results showing the median (horizontal black bar), Q1 (lower box), Q3 (upper box) and lower and upper limit. (F) Results represent mean ± SD. Statistical analysis: (A, B, C, D, E) Student’s t-test for independent samples, (F) one-way ANOVA. (*) indicates significant differences vs. control group; (‡) indicates significant differences vs. day 0, p < 0.05. Control group: N = 9; SNF472-treated group: N = 8.</p