Indomethacin Inhibits Renal Functional Adaptation to Nephron Loss

Abstract

Immediately after unilateral nephrectomy, the glomerular filtration rate (GFR) and urinary excretion rate increase in the remaining transplanted rat kidney. In a previous study, we found that GFR in a transplanted kidney was reduced through an activation of the tubuloglomerular feedback control. Excision of the rat’s own remnant kidney then reduced feedback sensitivity and thereby allowed GFR to rise. The present study aimed at investigating whether prostaglandins are involved in this functional adaptation. Clearance and micropuncture experiments were performed before and after administration of indomethacin and after subsequent unilateral nephrectomy. GFR and the urinary excretion rate of electrolytes and water were measured. From proximal tubular stop-flow pressure (P_SF) measurements the feedback characteristics were determined as the maximal stop-flow pressure response (ΔP_SF) to an increase in distal flow and the turning point (TP), i.e. the end proximal flow rate that caused 50% reduction of ΔP_SF. The results showed that following nephrectomy the tubuloglomerular feedback sensitivity was decreased, with an increased TP and reduced ΔP_SF. Pretreatment with indomethacin (2 mg/kg BW) prevented not only the change in feedback sensitivity at nephrectomy but also the rise in GFR. These results suggest that the prostaglandins play a possible role as one link in the chain of adaptive events occurring immediately after nephron loss.