Nature of the renal injury following total renal ischemia in man.

Abstract

As bstract. The effects of total renal ischemia (TRI) of 15-87 min duration due to suprarenal clamping of the aorta were studied in 15 mannitol-treated patients undergoing abdominal aortic surgery. 15 patients undergoing similar surgery but requiring only infrarenal clamping served as controls. 1-2 h following TRI, GFR was reduced to only 39% of that in controls, 23±5 vs. 59±7 ml/min (P < 0.001). This could not be ascribed to impaired renal plasma flow (RPF), which was mildly reduced to 331±71 and was not different from the value in controls, 407±66 ml/min. However, impaired PAH extraction (43±7%) and isosthenuria, not present in controls, suggest a primary role for tubular injury in lowering GFR at this time.24 h following TRI, the GFR remained depressed below controls, 45±8 vs. 84±8 ml/min (P < 0.005), while the transglomerular sieving of neutral dextrans was significantly enhanced (radius interval, 24-40 A). A theoretical analysis of transcapillary solute exchange revealed that these findings could be largely explained by a selective reduction of either RPF (-61%) or of transmembrane hydraulic pressure difference (-18%) below control values. Alternately, a combination of these two factors with changes of smaller magnitude could explain the findings. In contrast, a selective increase in oncotic pressure or decrease ofthe glomerular ultrafiltration coefficient could be excluded as a cause of hypofiltration 24 h after TRI. These observations lead us to suggest that the transient azotemia observed following TRI is due to a self-limited

Backleak, tight junctions, and cell- cell adhesion in postischemic injury to the renal allograft.

“…The reason for the finding that 3% of tubule cells have exfoliated into the lumen in our living donor control group is obscure. We speculate that handling of the donor kidney and the vascular pedicle before nephrectomy results in sufficient ischemic injury to account for this observation (5). We also note with interest that both on the day of transplant and on day 7 after transplant, we rarely observed an exposed segment of tubule basement membrane among the thousands of tubule cells that we examined by light or electron microscopy.…”

“…Studies of postischemic ARF in experimental animals that have used the techniques of nephron micropuncture have identified a reduction in filtration pressure, owing to a combination of afferent arteriolar constriction and tubular obstruction, as the major mechanism by which GFR is lowered (1)(2)(3). More indirect techniques point also to dissipation of filtration pressure as a principal cause of filtration failure in hemodynamically induced forms of ARF in humans (4)(5)(6).…”

Acute kidney injury: We’ve got the diagnosis, now what?

“…It takes 24-48 hr for the GFR to return to baseline, during which the SCr progressively increases until creatinine excretion again exceeds creatinine production. 12 Thus, in the early postoperative period after major aortic surgery, it is quite possible to observe an increasing SCr (and by definition AKI) while renal function is actually improving. In general, increases in SCr lag many hours or days behind declines in GFR, and it may take two to five days after an acute injury to the kidney before the SCr reaches a new steady state that reflects the nadir GFR.…”

“…Le DFG prend 24 à 48 heures pour revenir à la ligne de base, au cours desquelles la SCr augmente progressivement jusqu'à ce que, de nouveau, l'excrétion de créatinine dépasse sa production. 12 Ainsi, au cours de la période postopératoire précoce après chirurgie aortique majeure, il n'est pas rare d'observer une augmentation de la SCr (et, par définition, une LRA) alors que la fonction rénale est en fait en train de s'améliorer. D'une manière générale, les élévations de la SCr sont en retard de plusieurs heures ou jours derrière la baisse du DFG et il peut falloir de deux à cinq jours après une lésion aiguë du rein avant que la SCr n'atteigne à nouveau un nouvel état stable reflétant le nadir du DFG.…”

The Metamorphosis of Acute Renal Failure to Acute Kidney Injury

“…While this model may parallel human AKI after aortic surgery or renal transplantation, it greatly exaggerates the degree of tubular injury compared with that in the limited number of available human renal biopsies and is probably less relevant to AKI that does not follow hypoperfusion (Heyman et al (2010)). Even in this model there is limited understanding of how major pathophysiological events in AKI are integrated, for example, the mechanism and timing of the switching "off" and "on" of Myers et al (1984)), most of our experimental interventions have been validated only in this and nephrotoxic animal models ). While there is a great deal of information about a large number of cellular (tubular and endothelial) events and the autonomic, inflammatory and renal vascular responses in experimental ischemia-reperfusion injury (Devarajan (2006); Heemskerk et al (2009)), there is little corroborative and time-relevant clinical pathophysiological data.…”