The use of alkaline phosphatase in the treatment of reduced renal function
A technology of kidney function, phosphatase, applied in the medical field
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Embodiment 1
[0114] Example 1: Effect of AP on renal function in patients with sepsis
[0115] patient
[0116] Fifteen patients diagnosed with renal impairment in the intensive care unit were randomized to AP treatment (2AP:1 placebo).
[0117] After treatment, arterial blood and catheter urine were collected at several time points from 0 to 24 hours. Urine volume was recorded and samples for NO metabolite determination were frozen at -80°C prior to analysis described above (6). Creatinine and protein were determined by routine clinical chemistry.
[0118] intervene
[0119] Bovine intestinal alkaline phosphatase (AP, AM-Pharma, Bunnik, The Netherlands) was derived from the intestinal mucosa of calves <6 months of age. Eligible patients received AP or matching placebo (2.5 mM Tris-HCl, 2.5 mM magnesium chloride, 0.05 mM zinc chloride, pH 7.3, and 40% glycerol as a stabilizer) intravenously in a 2:1 ratio over 24 hours . Patients randomized to AP received an initial bolus injection o...
Embodiment 2
[0124] Example 2: Effect of AP on Renal Failure Caused by Gentamicin
[0125] The effect of alkaline phosphatase (AP) was evaluated in a gentamicin-induced nephrotoxicity model in Wistar rats. Gentamicin was given to the animals by intramuscular injection at 120 mg / kg for 7 consecutive days. Urine samples were collected within 24 hours on day 6 to determine urine volume, electrolytes (Na + 、K + ), creatinine, N-acetylglucosaminidase (NAG) and protein. Finally, blood samples were collected on day 7; serum creatinine, BUN, and electrolytes (Na + 、K + )concentration. The gentamicin-treated group (n=8 per group) was provided vehicle or AP (100 U / kg) by slow intravenous injection before daily administration of gentamicin, followed by additional administration every 12 hours for 7 consecutive days ( The sum of 14 AP doses=1400U / kg). The control group (n=8) received a single intraperitoneal injection of saline on day 0 and slow intravenous injection of vehicle using the same t...
Embodiment 3
[0126] Example 3: Effect of AP on cisplatin-induced renal failure
[0127] The effect of alkaline phosphatase (AP) on renal function was evaluated in Wistar rats after a single intraperitoneal injection of cisplatin at 7.5 mg / kg (designated as day 0). Urine samples were collected over 24 hours on days 2 and 5 to determine urine volume, electrolytes (Na + 、K + ), creatinine and protein. Blood samples were collected on days 3 and 6; serum creatinine, BUN, and electrolytes (Na + 、K + )concentration. Thirty minutes before receiving cisplatin injection, vehicle or AP (200 U / kg) was provided to the cisplatin-treated group (n=8 per group) by slow intravenous injection, followed by the second administration 12 hours later; Medication will continue on Day 1 (x 2) and Day 2 (x 1) for a total of 5 doses (total AP dose of 1000 U / kg). Control groups (n=8) received a single intraperitoneal injection of saline on day 0 and slow intravenous injection of vehicle using the same twice-dail...
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