TUBULOGLOMERULAR FEEDBACK - ITS PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL SIGNIFICANCE

The mammalian nephron has a unique structure called juxtaglomerular ap paratus (JGA); the primary function of the JGA includes tubuloglomerul ar 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 fil tration rate in the face of very limited salt intake of our terrestria l environment, a function essential to allow a wide range of fluid and electrolyte intake with stable milieu interieur. Salt intake in exces s is unique only to recent human cultures: salt intake is ordinarily l ess than 1 to 2 g per 60 kg of body weight in wildlife, including pale olithic humans. Any mutation or alteration of JGA function leading to renal salt conservation or maladaptive to high salt intake will not ma nifest in a low salt intake and thus would have been beneficial or inc onsequential 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 beha vior of human civilizations of recent centuries. The kidney has not ad apted to high salt intake through our evolution.