Tubuloglomerular feedback: its physiological and pathophysiological significance.

The mammalian nephron has a unique structure called juxtaglomerular apparatus (JGA); the primary function of the JGA includes tubuloglomerular feedback. Why is such a structure necessary? Analyses of available data strongly suggest that JGA has evolved to provide a fine tuning of the autoregulation of glomerular hemodynamics and high glomerular filtration rate in the face of very limited salt intake of our terrestrial environment, a function essential to allow a wide range of fluid and electrolyte intake with stable milieu interieur. Salt intake in excess is unique only to recent human cultures: salt intake is ordinarily less than 1 to 2 g per 60 kg of body weight in wildlife, including paleolithic humans. Any mutation or alteration of JGA function leading to renal salt conservation or maladaptive to high salt intake will not manifest in a low salt intake and thus would have been beneficial or inconsequential for survival in a natural environment, respectively. Thus, the mutation or alteration will be carried to subsequent generations. However, such altered function will result in essential hypertension or a maladaptation of JGA to high salt intake, which is a unique behavior of human civilizations of recent centuries. The kidney has not adapted to high salt intake through our evolution.