Although the role of
bacterial infection as the major determinant in the development of acute
pyelonephritis has been well documented for years, the nature of the renal
scarring typical of chronic "atrophic"
pyelonephritis has been a matter of controversy for at least three decades. In the past, recurrent
bacterial infection of the kidney was thought to be responsible for the pathologic entity of "chronic
pyelonephritis." However, more recent studies suggest that recurrent
bacteriuria, in the absence of some form of obstructive uropathy, rarely produces chronic
pyelonephritis. The close association between vesicoureteral reflex and chronic
pyelonephritis has also been firmly established and has been observed to occur frequently in the absence of
urinary tract infection. However, the mechanism by which
vesicoureteral reflux injures the kidney has not been firmly established. A number of observations have suggested that some normal component of urine, particularly
Tamm-Horsfall protein, might serve as an
antigenic determinant involved in the immunopathogenesis of renal
scarring in
vesicoureteral reflux. The present studies were designed to investigate the immunopathogenic role of
Tamm-Horsfall protein in a rabbit model of
tubulointerstitial nephritis, and in a swine model of reflux nephropathy. The immune responses to
Tamm-Horsfall protein in patients with recurrent
nephrolithiasis were also examined, as were the antigenic similarities between
Tamm-Horsfall protein and
protein-containing components of uropathic bacteria. The results of these studies indicate that autoimmune responses to
Tamm-Horsfall protein may occur after exposure to
Tamm-Horsfall protein by intravenous challenge in rabbits, and by urinary reflux in pigs, as well as in recurrent
nephrolithiasis in man.(ABSTRACT TRUNCATED AT 250 WORDS)