TUBULOINTERSTITIAL INJURY AND IMPAIRED RENAL-FUNCTION AFTER RECOVERY FROM ACUTE PUROMYCIN NEPHROSIS

Renal function was assessed at 2 and 8 wk after infusion of puromycin into the left renal artery of Munich Wistar rats. At 2 wk, albumin excretion averaged 90 +/- 12 mu g/min in the left kidney and 4 +/- 1 mu g/min in the right kidney. Unilateral nephrosis was accompanied by reduction in the glomerular filtration rate (GFR) (left, 0.71 +/- 0.04; right, 1.31 +/- 0.02 ml/min) and by impaired excretion of sodium (FE(Na); left, 0.025 +/- 0.004; right, 0.064 +/- 0.006%). Reductions in GFR and FE(Na) in the nephrotic kidney were not reversed by acute angiotensin II receptor blockade with losartan. At 8 wk, albumin excretion averaged 6 +/- 1 in the left kidney and 8 +/- 1 mu g/min in the right kidney. Recovery from nephrosis was accompanied by persistent reduction in GFR (left, 1.05 +/- 0.05 right, 1.41 +/- 0.05 ml/min) and impairment of sodium excretion in the previously nephrotic left kidney (left, 0.031 +/- 0.004; right, 0.051 +/- 0.004%). Losartan again did not return GFR and FEN, toward normal. The reductions in GFR and FEN, in the previously nephrotic left kidney were associated with structural changes, including intratubular casts, an increased fractional volume of the interstitium (left, 25 +/- 1; right, 15 +/- 1%), decreased fractional volume of tubules (left, 66 +/- 2; right, 77 +/- 1%), and glomerular collapse (left, 15 +/- 2; right, 1 +/- 1%). These findings suggest that tubulointerstitial. injury can cause persistent reduction in GFR and impairment of sodium excretion after recovery from acute nephrosis.