To determine the effects of
mannitol on the postischemic kidney rats were subjected to 25 minutes of renal artery occlusion and immediately after vascular clamp release they received a 2-ml intravenous
mannitol bolus (20%). Equimolar
urea-injected rats and
sham-injected rats served as controls. Postischemic renal blood flow, tubular metabolic work (renal O2 consumption),
adenine nucleotide pools, renal
oxidant stress (tissue
glutathione,
malondialdehyde levels), and tubular cell/mitochondrial swelling (histomorphometry) were assessed at variable times during the early vascular reflow period (15 to 60 minutes). The severity of
acute renal failure was determined by serial blood
urea nitrogen and serum
creatinine studies (24, 48 hours), and by renal histology (48 hours).
Mannitol increased postischemic renal blood flow (2-fold), renal O2 consumptions (3-fold), and urine flow compared to
urea-injected and
sham-injected controls. Postischemic
glutathione levels were equally depressed (reduced 33%) in all three treatment groups.
Malondialdehyde did not rise.
Mannitol significantly lowered total
adenine nucleotide content without changing
ATP at 15 minutes post renal artery occlusion. At 60 minutes post renal artery occlusion,
mannitol- and
urea-treated groups had comparable
ATP levels, 25% higher than the noninjected controls.
Mannitol and
urea induced comparable decrements in proximal tubular cell swelling, returning cell volumes to normal values. However, mitochondrial swelling was unabated.
Mannitol and
urea caused significant and nearly identical degrees of functional and morphologic amelioration of renal injury.
CONCLUSIONS:
Mannitol administered after renal
ischemia ameliorates both functional and morphologic aspects of acute tubular injury despite dramatically increasing tubular aerobic work. This protection appears not to be due to early postischemic improvements in
adenine nucleotide content, to increased renal blood flow, to increased urine flow, or to a lessening of
oxidant stress. The data are consistent with the view that protection results from acute hypertonic solute loading which either directly or indirectly decreases tubular cell but not mitochondrial swelling.