Detection of cell-cycle regulators in failed arteriovenous fistulas for haemodialysis.
BACKGROUND
Chronic renal failure (CRF) patients rely on arteriovenous fistulas (AVFs) for haemodialysis vascular access. Intimal hyperplastic stenoses result in failure of AVFs and frequent intervention is required to maintain vascular access. The extent of intimal hyperplasia depends on the interplay between cyclins and cyclin-dependent kinases (e.g. cdk2), positively regulating cell-cycle progression. cdk activity is negatively modulated by the interaction with cdk inhibitory proteins, such as p21(Waf1) and p27(Kip1). Little is known about the expression of these proteins in the development of intimal hyperplasia in AVFs.


METHODS
p21(Waf1), p27(Kip1), cdk2 and Proliferating Cell Nuclear Antigen immunoreactivity was determined in 18 failed AVFs from 16 CRF patients and 10 non-diseased vessels (five arteries and five veins).


RESULTS
The percentage of p21(Waf1)-positive cells was significantly lower in AVFs (3+/-1%), compared with normal veins and arteries (62+/-4 and 63+/-4%, respectively; P<0.001). cdk2-positive cells were significantly higher in AVFs (40.7+/-3.7%) than in normal veins and arteries (2+/-1 and 0+/-0%, respectively; P<0.001). Although no difference in p27(Kip1) immunoreactivity was found between AVFs (37+/-17%) and veins (23+/-8%; P=0.208), it was lower in healthy arteries (17+/-11%; P=0.037).


CONCLUSIONS
The data suggest that in failed AVFs, p21(Waf1), but not p27(Kip1), is related to intimal hyperplasia. This is the first report to show involvement of cell-cycle regulators in AVF-related human intimal hyperplasia.
de Graaf
Rick
R
Department of Surgery, University Hospital Maastricht, Maastricht, The Netherlands.
Dammers
Ruben
R
Vainas
Tryfon
T
Hoeks
Arnold P G
AP
Tordoir
Jan H M
JH
D000704:Analysis of Variance; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects* / Q000379:methods; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D018797:Cell Cycle Proteins / Q000032:analysis* / Q000378:metabolism; D003251:Constriction, Pathologic; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011336:Probability; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods*; D012680:Sensitivity and Specificity; D017539:Tunica Intima / Q000473:pathology*
D015415:Biomarkers; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases