ALTERATIONS IN RENAL TUBULAR EXTRACELLULAR-MATRIX COMPONENTS AFTER ISCHEMIA-REPERFUSION INJURY TO THE KIDNEY

BACKGROUND: The kidney is unique in that after ischemic injury to the renal tubules, essentially complete regenerative repair can occur. However, the factors responsible for renal regeneration are poorly delineated. Despite the importance of extracellular matrix components in cell attachment, proliferation, migration, and differentiation (all potentially important factors in regeneration), alterations in renal tubular extracellular matrix components after renal ischemia-reperfusion injury have not been examined. EXPERIMENTAL DESIGN: Rats were subjected to bilateral renal pedicle clamping for 45 minutes and kidneys were taken at various time points for light microscopy and laminin, fibronectin and collagen IV immunofluorescence examination. Blood was taken for plasma urea nitrogen and creatinine determination. RESULTS: Plasma creatinine and urea nitrogen rose rapidly peaking on days 1 to 3 (peak creatinine 3.2 +/- 0.3 mg/dl). The corticomedullary junction showed severe tubular necrosis and desquamation. Renal corticomedullary tubular basement membrane laminin showed a dramatic decrease at 18 hours through 24 to 48 hours postischemia-reperfusion injury, followed by a marked increase through day 5. Fibronectin increased markedly at 4 hours in all areas of the kidney and this continued through day 5. Type IV collagen remained unchanged at all time points examined. CONCLUSIONS: This study documents alterations in renal tubular basement membrane laminin and fibronectin after renal ischemia-reperfusion injury, The ability of the extracellular matrix to modulate cell functions of potential importance in regeneration suggests that the alterations described may play a role in renal tubular regeneration after ischemic acute tubular necrosis.