MECHANISMS OF FILTRATION FAILURE DURING POSTISCHEMIC INJURY OF THE HUMAN KIDNEY - A STUDY OF THE REPERFUSED RENAL-ALLOGRAFT

Postischemic filtration failure in experimental animals results primar ily from depression of the transcapillary hydraulic pressure differenc e (Delta P), a quantity that cannot be determined in humans. To circum vent this limitation we determined the GFR and each of its remaining d eterminants in transplanted kidneys. Findings in 12 allografts that ex hibited subsequent normofiltration (group 1) were compared with those in 11 allografts that exhibited persistent hypofiltration (group 2). D eterminations were made intraoperatively in the exposed graft after 1- 3 h of reperfusion. GFR (6 +/- 2 vs 29 +/- 5 ml/min) and renal plasma flow by Doppler how meter (140 +/- 30 vs 315 +/- 49 ml/min) were signi ficantly lower in group 2 than group 1, Morphometric analysis of glome ruli obtained by biopsy and a structural hydrodynamic model of viscous flow revealed the glomerular ultrafiltration coefficient to be simila r, averaging 3.5 +/- 0.6 and 3.1 +/- 0.2 ml/(min.mmHg) in group 2 vs 1 , respectively. Corresponding values for plasma oncotic pressure were also similar, averaging 19 +/- 1 vs 21 +/- 1 mmHg. We next used a math ematical model of glomerular ultrafiltration and a sensitivity analysi s to calculate the prevailing range for Delta P from the foregoing mea sured quantities. This revealed Delta P to vary from only 20-21 mmHg i n group 2 vs 34-45 mmHg in group 1 (P < 0.001). Further morphometric a nalysis revealed the diameters of Bowman's space and tubular lumens, a s well as the percentage of tubular cells that were necrotic or devoid of brush border, to be similar in the two groups. We thus conclude (a ) that Delta P depression is the predominant cause of hypofiltration i n this form of postischemic injury; and (b) that afferent vasoconstric tion rather than tubular obstruction is the proximate cause of the Del ta P depression.