On the mechanism of the splay in the glucose titration curve in advanced experimental renal disease in the rat.

Glucose titration studies were performed in rats with unilateral chronic pyelonephritis before and after removal of the contralateral control kidneys. Identical studies were performed in animals with unilateral partial renal infarction in which the experimental kidneys had a marked reduction in nephron population but no anatomic deformation in the surviving nephrons. In the initial studies, both groups of animals were free of clinical and chemical abnormalities of uremia. In the follow-up studies uremic abnormalities were present. Minimal splay was observed in the titration curves in the initial studies; marked splay was present in the group data from the same kidneys in the subsequent studies. Thus a marked reduction in the nephron population was associated with the evolution of splay in both groups of animals. In association with the increase in splay, the mean values for maximal glucose transport increased; thus a defect in glucose transport can be excluded as the basis of the splay. Glomerular filtration rate increased proportionately more than the maximal transport of glucose; hence the ratios of glomerular filtration rate to maximal glucose transport increased consistently. The possibility of asymmetric hypertrophy of glomerular and tubular functions among the nephron population imposed by scar tissue or other anatomic deformities was considered, but the results in the animals with partially infarcted kidneys militate against this explanation. The splay also could reflect an asymmetric alteration in the distribution of glomerulotubular balance among the residual units initiated by functional adaptations. Finally, the splay could relate to an alteration in the kinetics of glucose transport without any change in the level of functional homogeneity. The possible nature of these has been considered in the text.