Interaction of multiple risk factors in the pathogenesis of experimental reflux nephropathy in the pig

The importance of several pathogenetic factors in the development of reflux nephropathy was evaluated in 25 piglets with complete unilateral vesicoureteral reflux and urinary tract infection. Three independent risk factors were studied: 1) roentgenographic intrarenal reflux, 2) P-fimbriation of the bacterial strain, 3) absence of previous immunization. E. coli with P-fimbriae produce mannose-resistant agglutination of pig red blood cells and are more adherent to pig uroepithelial cells than E. coli without P-fimbriae. Vesicoureteral reflux was surgically indiced at 2 weeks, urinary tract infection introduced at 6 weeks and the animals killed at 12 weeks of age. Independently, the 3 risk factors had a borderline or insignificant effect on renal scarring. Animals with none or only 1 risk factor, however, had significantly less scarring, fewer glomerular lesions and lower serum creatinines than those with 2 or 3 factors present. Several independent pathogenetic factors seem to have a synergistic effect on the development of reflux nephropathy.