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Effect of leukocyte depletion on the function of the postobstructed kidney in the rat
K P Harris1, G F Schreiner, S Klahr
1Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Abstract:
We have observed an influx of leukocytes, predominantly macrophages, into the cortex and medulla of the kidney following ureteral obstruction. To examine the potential contribution of these infiltrating cells to the decrease in GFR and RPF that occurs following ureteral obstruction, 16 male Lewis rats (wt 246.4 +/- 4.0 g) were studied in the awake state three hours after unilateral release of 24 hours of bilateral ureteral obstruction (BUO). Eight rats were not irradiated, and eight rats received 1315 rads one day prior to the obstruction. The leukocyte infiltrate following 24 hours of ureteral obstruction was quantified with and without prior irradiation in an additional eight rats. Irradiation reduced cortical infiltration (27.05 +/- 3.07 x 10(5) vs. 1.2 +/- 0.83 x 10(5) cells/g tissue) and medullary infiltration (13.6 +/- 1.79 x 10(5) vs. 0.86 +/- 0.45 x 10(5) cells/g tissue) of leukocytes following BUO (P less than 0.001 for both) and increased postobstruction GFR (1.58 +/- 0.12 vs. 2.97 +/- 0.15 ml/min/kg body wt, P less than 0.001). Eleven rats, six of which received irradiation, underwent sham laparotomy without BUO in order to assess the effect of irradiation alone on renal function. Irradiation had no effect on the renal function of non-obstructed rats. Urinary excretion of thromboxane B2 increased following BUO and this rise was significantly blunted by irradiation prior to BUO (9.53 +/- 2.14 vs. 32.46 +/- 4.95 vs. 19.03 +/- 1.94 pg/min). Fractional excretion of sodium and water was reduced by irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Irradiation significantly reduced leukocyte infiltration in kidneys after ureteral obstruction, improving kidney function and blunting thromboxane B2 excretion. This suggests leukocytes contribute to obstruction-induced kidney injury.
Area of Science:
- Nephrology
- Immunology
- Renal Physiology
Background:
- Ureteral obstruction leads to kidney injury, characterized by leukocyte infiltration and decreased glomerular filtration rate (GFR) and renal plasma flow (RPF).
- The role of infiltrating leukocytes, particularly macrophages, in mediating kidney dysfunction following ureteral obstruction is not fully understood.
Purpose of the Study:
- To investigate the contribution of infiltrating leukocytes to the decline in GFR and RPF following bilateral ureteral obstruction (BUO).
- To assess the effect of irradiation on leukocyte infiltration and renal function after BUO.
Main Methods:
- Male Lewis rats underwent 24 hours of BUO, with some receiving irradiation prior to obstruction.
- Leukocyte infiltration in the renal cortex and medulla was quantified.
- GFR and urinary thromboxane B2 excretion were measured.
- Fractional excretion of sodium and water was assessed.
Main Results:
- Irradiation significantly reduced cortical and medullary leukocyte infiltration following BUO (P < 0.001).
- Irradiation increased post-obstruction GFR (P < 0.001) and blunted the rise in urinary thromboxane B2 excretion.
- Irradiation did not affect renal function in non-obstructed rats.
Conclusions:
- Leukocyte infiltration into the kidney following ureteral obstruction contributes to the observed decrease in renal function.
- Irradiation mitigates kidney injury following ureteral obstruction by reducing leukocyte infiltration and associated inflammatory responses.