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1 Division of Nephrology, 2 Department of Radiology, 3 Department of Pathology, and 4 Department of Transplant Surgery, Stanford University School of Medicine, 5 Division of Biostatistics, Department of Health Research Policy, Stanford University, Stanford, California 94305; and 6 Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Postischemic injury in 38 recipients of 7-day-old cadaveric renal allografts was classified into
sustained (n = 15) or recovering (n = 23) acute renal failure (ARF) according to the prevailing inulin
clearance. Recipients of long-standing allografts that functioned
optimally (n = 16) and living transplant donors
undergoing nephrectomy (n = 10) served as functional
and structural controls, respectively. A combination of physiological
and morphometric techniques were used to evaluate glomerular filtration
rate and its determinants 1-3 h after reperfusion and again on
day 7 to elucidate the mechanism for persistent
hypofiltration in ARF that is sustained. Glomerular filtration rate in
the sustained ARF group on day 7 was depressed by 90%
(mean ± SD); the corresponding fall in renal plasma flow was
proportionately less. Neither plasma oncotic pressure nor the
single-nephron ultrafiltration coefficient differed between the
sustained ARF and the control group, however. A model of glomerular
ultrafiltration and a sensitivity analysis were used to compute the
prevailing transcapillary hydraulic pressure gradient (
P), the only
remaining determinant of P. This revealed that P varied between
27 and 28 mmHg in sustained ARF and 32-38 mmHg in recovering ARF
on day 7 vs. 47-54 mmHg in controls. Sustained ARF was
associated with persistent tubular dilatation. We conclude that
depression of P, perhaps due partially to elevated tubule pressure,
is the predominant cause of hypofiltration in the maintenance stage of
ARF that is sustained for 7 days.
filtration dynamics; glomerular morphometry; tubule morphometry; ultrafiltration coefficient; filtration pressure
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