Ureteral obstruction reverses glomerular proliferation in immune complex glomerulonephritis

We investigated an effect of ureteral obstruction on a progressive immune complex glomerulonephritis in murine lupus erythematosus. Unilateral ureteral obstruction for 8 days significantly decreased the expanded glomerular mesangial area, as measured by computer-assisted morphometry (4.44 +/- 0.33 x 10(-4) mm2 to 3.60 +/- 0.34 x 10(-4) mm2, P < .05), and reduced the staining for IgG, C3, and extracellular matrix components, whereas the nephritis was exacerbated in the contralateral non-obstructed kidney. The renal concentration of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) in the obstructed kidneys 8 days after obstruction significantly exceeded that of kidneys in sham-operated controls (344.2 +/- 83.9 pg/mg tissue protein vs 50.0 +/- 27.5 pg/mg tissue protein, P < .01; 71.9 +/- 11.4 pg/mg tissue protein vs 9.5 +/- 2.3 pg/mg tissue protein, P < .01), whereas thromboxane B2 (TxB2) levels were similar in the two groups (33.9 +/- 4.5 pg/mg tissue protein vs 31.3 +/- 2.6 pg/mg tissue protein). Next, an experiment was performed to evaluate the role of renal eicosanoids in the amelioration in the immune complex glomerulonephritis after ureteral obstruction. Treatment with the cyclooxygenase inhibitor indomethacin abolished the decrease in mesangial area induced by ureteral obstruction (7.7% +/- 6.9%). CV-4151, a thromboxane synthetase inhibitor, had no effect on the decrease in mesangial area (-25.8% +/- 6.8%, P < .05). We conclude that unilateral ureteral obstruction quickly decreased the mesangial expansion in immune complex glomerulonephritis, and vasodilatory eicosanoids such as PGE2 and PGI2 at least partly contribute to the amelioration of glomerular histology.