Correlation between Renal Growth Retardation and Apoptosis of Cortical Tubules in Experimentally Induced Acute Ascending Pyelonephritis in Infant Rat

Sung, Sun Hee; Woo, Soyoun; Lee, Seung Joo

Abstract

The infant kidney is more vulnerable to infections than the adult kidney. It is common that acute pyelonephritis (APN) during infancy and early childhood manifests growth retardation of kidney, ultimately leading to chronic renal failure. However, little is known about the pathogenesis of renal growth retardation in APN in youth. To understand the mechanism underlying the cortical lesions, urinary tract infection was induced in infant rats. To induce ascending APN, saline solution containing Escherichia coli (ATCC No. 25922) 107 bacteria/ml was infused into the bladder through the 16 gage silicone cannula in three-week-old weaning Sprague Dawley rats (weight 50~60 g, n=66). In the normal control group (n=20), saline was infused. Experimental groups were divided according to the treatment into the APN group (APN without any treatment, n=23) and TRX group (APN with ceftriaxone treatment, n=23). After performing the histopathologic examination, including inflammatory score, fibrosis score, and tubular atrophy score, we measured the apoptosis index in the tubular cells of noninflammatory cortical area at post-infection week 1 and 3 by the in situ TUNEL method. Kidney weight was significantly decreased in the APN group compared with the normal group at postinfection week 1 and 3. In the APN group, tubulointerstitial inflammation with heavy neutrophilic infiltration was found mainly in the upper and lower poles of the kidney in both the first and third week groups. Fibrosis was dominant in the third week of the APN group. However, inflammation and fibrosis were not significantly improved by TRX treatment. The apoptotic index of tubular cells was significantly increased in noninflammatory cortical area in the first week of both APN and TRX groups. It decreased near the normal control value in the third week. TGF-beta1 protein expression was localized in the inflammatory area. There was no TGF-beta1 expression in the tubules of the noninflammatory area. These findings suggest that renal growth retardation in experimentally induced APN in infant rats is related not only with the inflammatory reaction itself but also with the increased apoptosis of tubular cells in noninflammatory area. Ceftriaxone alone does not eliminate the inflammation nor prevent growth retardation effectively.