Reset tubuloglomerular feedback permits and sustains glomerular hyperfunction after extensive renal ablation

Abstract

To determine the contribution of the tubuloglomerular feedback (TGF) system to glomerular hyperfunction after extensive loss of renal mass, TGF was assessed in anesthetized Sprague-Dawley rats 7 days after 5/6 reduction of renal mass (2/3 infarction of 1 kidney plus contralateral nephrectomy) or sham surgery. Five-sixths renal ablation significantly increased single-nephron (SN) glomerular filtration rate (GFR) 57%, late proximal tubule fluid flow 58-63%, and maximal proximal tubule stop-flow pressure (PSF) 24%. Despite these increments, 5/6 ablation did not increase TGF activation, as judged by the difference between proximally and distally measured SNGFR values, nor did it affect maximal TGF responses, measured as change in PSF during forward microperfusion of the loop of Henle. However, 5/6 ablation increased the late proximal perfusion rate eliciting half-maximal PSF suppression (V1/2) from 27.3 +/- 1.6 to 45.7 +/- 2.4 nl/min (P less than 0.001), a change closely matching the increment in native late proximal tubule fluid flow from 26.6 +/- 2.2 to 43.8 +/- 2.1 nl/min (P less than 0.001). Unilateral nephrectomy increased V1/2 less dramatically than did 5/6 ablation, thus showing that the effects of renal ablation on TGF are proportional to the degree of ablation. We conclude that extensive renal ablation resets TGF operation in a way that permits and helps sustain glomerular hyperfunction.