Response of the human kidney to clamp ischemia.

Abstract

365 Background: Structural changes in tubule cells during clamp ischemia are well characterized for animal models, but their timing and extent in the human kidney has not been established and may differ significantly. To better define the human response, we biopsied uninvolved areas of kidney in patients undergoing open partial nephrectomy for renal masses. Methods: Biopsies of 40 patients undergoing PN were obtained at specified time intervals: before renal artery clamping, then during periods ranging from 15 to 60 min. of warm and cold ischemia (80% > 30 min.), and then after 5 minutes of reflow. These biopsies were assessed for ultrastructure (N=39) and for immunofluorescence and rhodamine phalloidin staining (N=22). Results: During the clamp period, apical membrane structure was remarkably well preserved with only patchy brush border clubbing, fragmentation, desquamation and blebbing and not in all patients. Mitochondria developed progressive swelling, which paradoxically was more prominent in distal than proximal tubule cells. This resolved during the 5 minutes of reflow in most cells in most patients, but persistence of swelling and development of matrix condensation occurred occasionally. Using a composite 0-5 scale covering the full spectrum of ultrastructural changes, average scores were: Preclamp 1.02±0.07, End clamp 2.18±0.07, Post clamp 1.86±0.09. Consistent with the ultrastructure, staining for F-actin with rhodamine phalloidin was well preserved. Immunsotaining for phosphotyrosine, which reflects cellular ATP content was decreased in 68.4% of the clamp biopsises and 52.6% of the postclamp biopsies with larger changes in proximal tubules, however B1 integrin was decreased in only one post clamp biopsy. ICAM-1 expression in peritubular capillaries was increased in 46.7% of the clamp biopsies and 66.7% of post clamp biopsies. None of the patients developed acute kidney injury. Conclusions: These data provide the first detailed analysis of the structural response of the human kidney to clamp ischemia and document many of the expected structural alterations based on prior animal work, but indicate a greater than expected resistance to injury in this commonly used clinical application of clamp ischemia.