Evidence for activation of tubuloglomerular feedback following nephrectomy in human subjects.

The intrarenal regulation of glomerular filtration rate (GFR) following a reduction in renal mass was evaluated in six normal subjects, studied before and 4 to 6 weeks after undergoing unilateral nephrectomy, performed for the purpose of living-related transplantation. The role of the tubuloglomerular feedback (TGF) system in regulating the final GFR on both occasions was assessed by determining the increase in GFR over baseline levels following blockade of TGF by a single dose of bumetanide, care being taken to replace sodium and water losses. Before donor nephrectomy, baseline GFR was 115 +/- 7 mL/min, which increased by 9.5% +/- 2.5% to 126 +/- 9 mL/min following the removal of TGF. Four to six weeks following donor nephrectomy, the baseline GFR was 83 +/- 8 mL/min, confirming significant hyperfiltration in the remaining kidney. After administration of bumetanide, the GFR increased by 15.6% +/- 3.1% to 96 +/- 9 mL/min. This greater fractional increase (P < 0.025) indicates an increase in tonic TGF activity in the uninephrectomized state compared with that demonstrated before nephrectomy. The results suggest that the hyperfiltration response following unilateral nephrectomy is limited by an appropriately activated TGF system. This phenomenon may be of importance in the maintenance of Na and water homeostasis, as well as limiting the pathological consequences that may result from, or be exacerbated by, an excessively high filtration rate in the remaining nephrons. Thus, dietary or therapeutic maneuvers that impair the TGF response may be best avoided following a reduction in renal mass.