Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and chronic allograft nephropathy

Archil B. Chkhotua, Elena Gabusi, Annalisa Altimari, Antonia D'Errico, Michaela Yakubovich, Joerg Vienken, Sergio Stefoni, Pasquale Chieco, Alexander Yussim, Walter F. Grigioni

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Abstract

Background: 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). Methods: 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. Results: 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 R2:0.370, 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 interstital cells was higher in grade 3 of CAN than in grade 2 (P = 0.013 and 0.004, respectively). Conclusion: 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.

Original languageEnglish
Pages (from-to)1303-1313
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

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Keywords

  • Chronic allograft nephropathy
  • Cyclin-dependent kinase inhibitors
  • Kidney senescence
  • Kidney transplantation
  • P16
  • P27

ASJC Scopus subject areas

  • Nephrology

Cite this

Chkhotua, A. B., Gabusi, E., Altimari, A., D'Errico, A., Yakubovich, M., Vienken, J., Stefoni, S., Chieco, P., Yussim, A., & Grigioni, W. F. (2003). Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and chronic allograft nephropathy. American Journal of Kidney Diseases, 41(6), 1303-1313. https://doi.org/10.1016/S0272-6386(03)00363-9