The pathogenesis of reflux nephropathy (chronic atrophic pyelonephritis)

The relationship between vesico-ureteric reflux and coarse renal scarring (atrophic pyelonephritis) has been studied in swine. Scars were observed to develop where reflux took place into the kidney substance via the renal papillae (intrarenal reflux). They were confined to these regions and were similar in size, distribution and other features peculiar to those found in the human from early childhood onwards. Intrarenal reflux was found to be related to the pressure within the urinary tract as well as to vesico-ureteric reflux. Infection was not an essential factor in scar-formation, but it appeared to intensify the scarring process. The histological findings were a progressive focal interstitial fibrosis confined to the zones of intrarenal reflux, extending from the capsule to the papillary tip, and varying in severity with pressure, time and the extent of intrarenal reflux. Nephron and tubular damage accompanied all grades of fibrosis, with the possible exception of the earliest. In many respects the histological changes closely resemble those due to obstruction, except they are focal in distribution. Added features are the early peripheral lymphocytic aggregations and interstitial fibrosis which appear to suggest that some "irritant"--possibly urine--reaches the interstitium and drains away via the lymphatic system. Many of the phenomena observed were strikingly similar to those present in children with the more severe grades of vesico-ureteric reflux. In some cases a mixture of generalized obstructive nephropathy and focal scarring developed; in others focal scarring took place with normal papillae elsewhere. The results are readily reproducible. The basic questions as to whether it is bladder pressure, or infection, or a mixture of the two which is responsible for scar-formation are discussed.