The value and limitations of L-arginine infusion on glomerular and tubular function in the ischemic/reperfused kidney.
OBJECTIVE
The nitric oxide precursor, L-arginine, has been shown to have a salutary effect on ischemia and reperfusion injury in skeletal muscle, skin, and intestines. Because L-arginine also increases renal blood flow, glomerular filtration, and urine flow in experimental animals with normal renal function, we postulated that L-arginine may also improve renal function after renal ischemic injury.


METHODS
Eighteen adult New Zealand white rabbits weighing 3 to 3.5 kg were subjected to bilateral normothermic renal ischemia by clamping both renal pedicles for 1 hour followed by 2 hours of reperfusion. The animals were randomized into three groups: group I (control, n = 6) received no additional treatment; group II (pretreatment, n = 6) received systemic intravenous L-arginine at 150 mg/kg over 20 minutes before induction of ischemia; group III (posttreatment, n = 6) received systemic intravenous L-arginine at 150 mg/kg over 20 minutes from the onset of reperfusion. Urine flow, creatinine clearance (CCR), fractional excretion of sodium (FENa), and renal failure index (RFI) were calculated before ischemia and 2 hours after reperfusion, by use of standard formulas. The changes of the various renal parameters were compared among the three groups.


RESULTS
Bilateral normothermic renal ischemia for 1 hour produced a significant deterioration of glomerular filtration as evidenced by a CCR decrease from 11.1 +/- 1.8 to 2.49 +/- 0.9 ml/min (p < 0.01), FENa increase from 2.9% +/- 1.0% to 20.8% +/- 1.5% (p < 0.01) and RFI increase from 4.0 +/- 1.3 to 28.8 +/- 2.6 (p < 0.01). Pretreatment with L-arginine (group II) minimized the deleterious effects caused by ischemia on glomerular filtration (CCR of 2.49 +/- 0.9 ml/min in group I vs 4.95 +/- 2.5 ml/min in group II, p < 0.05) and tubular function (FENa of 20.8% +/- 1.5% in group I vs 13.0% +/- 5.6% in group II and RFI of 28.8 +/- 2.6 in group I vs 18.6 +/- 8.0 in group II, p < 0.05). Infusion of L-arginine at the onset of reperfusion (group III) produced a significant diuretic effect (urine flow from 32.6 +/- 13.4 ml/hr in group I to 63.3 +/- 18.8 ml/hr in group III, p < 0.05) and also minimized glomerular damage (CCR from 2.49 +/- 0.9 ml/min in group I to 4.80 +/- 1.2 ml/min in group III, p < 0.05); however, no beneficial effect was observed on tubular function.


CONCLUSIONS
Induction of nitric oxide production by systemic L-arginine infusion can best preserve glomerular and tubular function in the ischemic/reperfused kidney when given before the ischemic insult.
Dagher
F
F
Maimonides Medical Center, Division of Vascular Surgery, Brooklyn, New York 11219.
Pollina
R M
RM
Rogers
D M
DM
Gennaro
M
M
Ascer
E
E
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply; D007678:Kidney Glomerulus / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis*; D011817:Rabbits; D011897:Random Allocation; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*
D009569:Nitric Oxide; D001120:Arginine