Feedback activation in rat nephrons by sera from patients with acute renal failure

Tubuloglomerular feedback (TGF) may be triggered by varying the distal electrolyte load. TGF may contribute to acute renal failure (ARF), but maximal TGF stimulation induces only relatively small alterations in single nephron GFR (SNGFR) and stop-flow pressure (SFP), whereas in ARF, GFR may cease, raising the possibility that substances eliciting greater TGF responses than do elelectrolytes occur in ARF. We have sought such substances in serum, urine, and peritoneal fluid from patients with ARF. Sera samples from 1 healthy subject, 4 ARF patients, and 2 other anuric patients were dialyzed against glucose to reduce electrolyte concentrations and perfused through Henle's loops in salt-deplete rats. With ARF sera, SFP fell from 35.6 +/- (SD) 3.5 to 20.9 +/- 3.4 mm Hg (P less than 0.005) and SNGFR from 28.5 +/- 8.7 to 12.6 +/- 7.3 nl/min (P less than 0.005). Furosemide (10(-4) M) did not abolish the response. Perfusion with other patients' sera had no effect on SFP. ARF urine or peritoneal fluid induced similar responses. Conclusion. In some ARF patients, substances present in serum activate TGF in the rat. These substances might contribute to development of certain forms of human ARF, particularly ARF associated with liver dysfunction (hepatorenal syndrome).