Apoptosis and resolution of experimental renal infective tubulointerstitial nephritis

Resolution of tubulointerstitial nephritis represents an important step in limiting renal fibrogenesis. However, the mechanism of this resolution remains poorly understood. To determine if apoptosis has a role in this process, we studied its incidence in an experimental model of renal infection and scarring, induced by direct inoculation of Escherichia coli into the renal cortex of Sprague-Dawley rats. The focal lesion produced was studied in animals killed at various time points up to 100 days post inoculation. Apoptosis was identified by electron microscopy (EM) and in-situ labelling of fragmented DNA using terminal transferase-mediated deoxy-uridine-5'-triphospate (UTP) nick end labelling (TUNEL). Results were compared with morphological assessment of tubulointerstitial cellularity and macrophage localization. Terminal transferase-mediated UTP nick end labelling localized apoptosis to interstitial cells, tubular casts and occasional tubular epithelia and double labelling demonstrated apoptotic body incorporation in macrophages. Interstitial cellularity was maximum at day 3, decreasing significantly by 100 days (P<0.01). The incidence of interstitial apoptosis was increased by 3 days and remained significantly higher than day 0 controls throughout (P<0.05). Tubular cellularity was significantly less than in control animals throughout the experimental time period. Although the rate of tubular apoptosis was increased, this difference was not statistically significant. In conclusion, apoptosis may represent an important mechanism in the reduction of tubulointerstitial cellularity after experimental renal infection. This in rum, may be important in limiting subsequent interstitial scarring.