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The strong association between childhood urinary tract infection (UTI), vesicoureteric reflux (VUR) and kidney scarring has been recognised for many years,1 2 but their relationship is inconsistent. This is in part because many infants with UTIs only have non-specific symptoms and are not diagnosed, in part because children may scar while they have VUR and subsequently outgrow it,3 and in part because some dysplastic lesions are present from birth. The relationship was also in part unexplained because some kidneys were recognised not to scar despite having VUR and recurrent UTIs. Particularly striking are children with severe bilateral VUR where one kidney is extensively damaged and the other is pristine. Ransley and Risdon’s piglet experiments in the 1970s provided a possible explanation for these variations.4
By inducing unilateral VUR surgically in piglets and then introducing a bladder infection, Ransley and Risdon showed that the combination of VUR and a UTI caused coarse renal damage which closely resembled human kidney scarring, with dead segments adjacent to unaffected ones.4 They then showed that this pattern was related to the morphology of the individual renal pyramids: segments with nipple-shaped tips did not scar, whereas flattened and compound ones did. In the latter, the refluxing infected urine entered the parenchyme via the collecting ducts (intra-renal reflux) causing inflammation and the subsequent death of that segment.5 They showed that just one brief UTI could cause permanent damage6 (the “big-bang” concept). They also showed that about 70% of children’s kidneys had similar, apparently vulnerable papillae, predominantly at the poles where human kidney scars are commonest.7 Thus, Ransley and Risdon provided a model that explained much about renal scarring in children, apparently justifying the clinical term “reflux nephropathy”.8
In the 1980s it was suggested that UTIs could occasionally initiate scarring …
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