Paleonephrology and reflux nephropathy. From the 'big bang' to end-stage renal disease

Urinary tract infections, in association with ureteral reflux or dysperistalsis, may lead to invasive renal parenchymal infection and residual scarring (reflux nephropathy). Such infections in infants are often not diagnosed during the acute phase. Late sequelae of reflux nephropathy include hypertension, proteinuria, or chronic renal failure. The latter may eventuate in the subset of patients with urinary tract infection and unilateral reflux extending to a solitary kidney or bilateral reflux. Proteinuria may herald the inexorable progression of glomerular sclerosis in patients destined to progress to end-stage renal disease, despite the absence of further recurrences of urinary tract infections. The mechanism of progression is probably similar to that occurring in other forms of chronic, diffuse parenchymal renal disease, which all have similar alterations in glomerular hemodynamics (an increase in glomerular capillary flow, pressure, and filtration). The consequent hyperfiltration per nephron may be related to the level of dietary protein intake or to some derivative of the protein load. Hyperfiltration appears to recapitulate the presumed renal hemodynamic response to the relatively high level of episodic meat consumption by paleolithic hunter-gatherers. A prudent therapeutic intervention in children with progressive reflux nephropathy may be a proportional reduction in protein intake.