Tubulointerstitial disease in aging: Evidence for underlying peritubular capillary damage, a potential role for renal ischemia

Susan E. Thomas, Sharon Anderson, Katherine L. Gordon, Terry T. Oyama, Stuart J. Shankland, Richard J. Johnson

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Abstract

Aging is associated with a progressive decline in renal function and the development of glomerulosclerosis and interstitial fibrosis. Although many studies have addressed the cellular mechanisms of age-related glomerulosclerosis, less is known about the tubulointerstitial fibrosis. In this study, aging (24 mo) rats develop tubulointerstitial fibrosis characterized by tubular injury and focal tubular cell proliferation, myofibroblast activation, macrophage infiltration with increased immunostaining for the adhesive proteins osteopontin and intercellular adhesion molecule-1, and collagen IV deposition. Aging rats demonstrated immunostaining for endothelial nitric oxide synthase (eNOSIII) in renal tubular epithelial cells and infiltrating mononuclear cells in areas of tubulointerstitial injury, with a relative loss of staining of the peritubular capillaries compared with young rats. The aging rats also displayed focal loss of peritubular capillaries (as noted by focally decreased RECA-1 and OX-2 staining) in areas of tubulointerstitial injury. The areas of fibrosis and hypocellularity were associated with increased apoptosis of tubular and interstitial cells compared with young (3 mo) rats (25.4 ± 5.3 versus 3.5 ± 2.5 TUNEL-positive cells/0.25 mm2 in old versus young rats, P = 0.0001). It is concluded that tubulointerstitial fibrosis in aging is an active process associated with interstitial inflammation and fibroblast activation. The progressive loss of cells in areas of fibrosis may be due to accelerated apoptosis. Furthermore, the tubulointerstitial injury may be the consequence of ischemia secondary to peritubular capillary injury and altered eNOS expression.

Original languageEnglish (US)
Pages (from-to)231-242
Number of pages12
JournalJournal of the American Society of Nephrology
Volume9
Issue number2
StatePublished - Feb 1998

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Fibrosis
Ischemia
Kidney
Wounds and Injuries
Apoptosis
Staining and Labeling
Osteopontin
Myofibroblasts
Macrophage Activation
Nitric Oxide Synthase Type III
In Situ Nick-End Labeling
Intercellular Adhesion Molecule-1
Adhesives
Collagen
Fibroblasts
Epithelial Cells
Cell Proliferation
Inflammation
Proteins

ASJC Scopus subject areas

  • Nephrology

Cite this

Tubulointerstitial disease in aging : Evidence for underlying peritubular capillary damage, a potential role for renal ischemia. / Thomas, Susan E.; Anderson, Sharon; Gordon, Katherine L.; Oyama, Terry T.; Shankland, Stuart J.; Johnson, Richard J.

In: Journal of the American Society of Nephrology, Vol. 9, No. 2, 02.1998, p. 231-242.

Research output: Contribution to journalArticle

Thomas, Susan E. ; Anderson, Sharon ; Gordon, Katherine L. ; Oyama, Terry T. ; Shankland, Stuart J. ; Johnson, Richard J. / Tubulointerstitial disease in aging : Evidence for underlying peritubular capillary damage, a potential role for renal ischemia. In: Journal of the American Society of Nephrology. 1998 ; Vol. 9, No. 2. pp. 231-242.
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