The goal of the current study was to examine the potential value of p16(INK4a) and
p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes in the process of human kidney
aging in vivo, and in the development of chronic allograft nephropathy (CAN).
Expression of p16(INK4a) and p27(Kip1) CDKI genes was evaluated and compared in 20
normal human kidney tissues of different ages (range, 21 to 80 years) and in 9 chronically
rejected kidney grafts. Age dependency of marker expression was analyzed by the Pearson
correlation and linear regression.
Expression of p16 in cortical tubular (CTS) and interstitial (CIS) cells of normal
kidney was age dependent (correlation coefficients: 0.608 and 0.726, 95% confidence
interval [CI]: 0.227 to 0.828 and 0.417 to 0.884, respectively). Cortical tubular
expression of p27 was also correlated with increasing age (0.672, 95% CI: 0.327 to
0.859). Linear regression analyses confirmed the linearity of marker relationship
with age (coefficient of determination R(2):0.370, 0.452, and 0.527 for CIS p16, CTS
p27, and CTS p16, respectively). The mean chronological and predicted graft ages (53
+/- 21 and 76 +/- 8.9 years, respectively) were significantly different (P = 0.0126).
The glomeruli, tubules, and interstitial cells of rejected grafts expressed significantly
higher levels of p16 and p27 than normal kidneys. Expression of p16 in glomerular
and cortical interstitial cells was higher in grade 3 of CAN than in grade 2 (P =
0.013 and 0.004, respectively).
The results of the current study show that expression of p16(INK4a) and p27(Kip1)
CDKI genes is increased in cortical cells of the aging human kidney and in chronic
allograft rejection, supporting the senescence theory of CAN.