Evaluation of the tubuloglomerular feedback system in human subjects

It has been shown in animals that GFR decreases after administration of a carbonic anhydrase inhibitor (CAI) because of activation of the tubuloglomerular feedback. However, the magnitude of this response has never been studied in healthy subjects, nor has the possibility of inhibiting tubuloglomerular feedback with frusemide (FRU). Changes in CCr, V, CNa, CCl, CH2O, CLi were studied before and after acute administration of acetazolamide (ACZ) to 11 normal subjects or FRU to 9 normal subjects. Both ACZ and FRU increased V, CNa, CCl and CLi. Only FRU decreased CH2O. ACZ but not FRU decreased CCr, despite lesser increases of V, CLi and CH2O+CCl (rough indexes of distal delivery). The magnitude of the GFR decrease after comparable increases in distal delivery varied greatly between subjects. There was a tendency for the subjects with lower basal GFRs to show tubuloglomerular feedback responses of lesser magnitude than those with higher GFRs. These results show that it is possible to study tubuloglomerular feedback and its sensitivity in humans using CAIs. FRU blocks the tubuloglomerular feedback response. Its sensitivity appears to vary widely in normal subjects.