BACKGROUND: The high rate of @entity65 in @entity1 with @entity454 ( @entity454 ) is a significant barrier to improved life expectancy. Unique in this population is the marked development and @entity146 worsening of @entity729 ( @entity729 ). @entity9955 ( @entity7371 ), an endogenous molecule, appears to naturally inhibit soft tissue @entity730 , but may be @entity740 ( @entity740 ) and @entity454 . Although once thought to be a promising therapeutic, @entity7371 's very short half-life in circulation curtailed earlier studies. We tested the possibility that a slow, continuous entry of @entity7371 into the circulation and prevention of @entity729 might be achieved by daily @entity298 ( @entity298 ). METHODS: Pharmacokinetic studies were first carried out in @entity35 with @entity8 resulting from a 5/6 nephrectomy. Efficacy studies were then performed in the @entity6970 gene knockout @entity19 model overlaid with @entity740 . @entity7371 was delivered by means of a permanent peritoneal catheter in a solution simulating @entity298 , but without the timed removal of spent dialysate. von Kossa's staining followed by semiquantitative morphological image processing, with separation of inside (intimal) and outside (presumed medial) lesions, was used to determine aortic root @entity730 . RESULTS: In comparison to an intravenous bolus, delivery of @entity7371 in a @entity298 solution resulted in a slower, extended delivery over >4 h. Next, the efficacy studies showed that a 6-day/week @entity298 -simulated administration of @entity7371 resulted in a dose-dependent inhibition of @entity730 in both intimal and medial lesions. A dose-response effect on total @entity730 was also documented, with a full inhibition seen at the highest dose. A limited peritoneal catheter-related @entity32 was observed, as expected, and included the placebo-treated control groups. This inflammatory response could have masked a lower level @entity7371 -specific adverse effect, but none was observed. CONCLUSIONS: Our findings suggest potential for @entity7371 , administered during @entity298 , to prevent the development of @entity729 and to potentially extend the life of @entity454 @entity1 .

Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of @entity729 in a XXXX model of uraemia.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity8 :: ('MESH:D007674', 'Disease') :: ['renal impairment'] @entity6970 :: ('11816(Tax:10090)', 'Gene') :: ['apolipoprotein E'] @entity7371 :: ('CHEBI:60614', 'Chemical') :: ['PPi'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive'] @entity298 :: ('MESH:D010538', 'Disease') :: ['peritoneal dialysis', 'PD'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity740 :: ('MESH:D051436', 'Disease') :: ['depressed in chronic kidney disease', 'CKD'] @entity730 :: ('MESH:D002114', 'Disease') :: ['aortic calcification', 'calcification'] @entity729 :: ('MESH:D061205', 'Disease') :: ['vascular calcification', 'VC'] @entity9955 :: ('MESH:C107241', 'Chemical') :: ['Pyrophosphate'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular mortality'] @entity454 :: ('MESH:D007676', 'Disease') :: ['end-stage renal disease', 'ESRD']
@entity19 :: (10090,Species) :: ['mouse']
