The nature of experimental second-set kidney transplant rejection. 4. The disturbed haemodynamics and the general significance of failure to perfuse the outer cortical glomeruli in acute renal failure.

The second-set reaction can be mimiced from a haemodynamic point of view by pharmacological vasopressors, warm and cold ischaemic factors producing vasocontriction and by the Shwartzman reaction. The second-set kidney transplant reaction is assumed to be due to antibodies which, if so, are not dependent for their cytotoxicity on complement fixation and are uninfluenced by antihistamine drugs, steroids, immunosuppression, incoagulable blood, adequate hydration and rheomacrodex. Once started, the reaction continues until the vasoconstriction is so severe that no blood enters the kidney and complete disorganization of kidney function and structure ensues. The deposition of fibrin in the vessels and glomeruli follows the severe vasomotor upset which evokes afferent vasoconstriction. Fibrin is not prevented from being deposited when the recipient of a second-set kidney is fully Arvinized so that the blood is rendered incoagulable. The second-set kidney reaction is first heralded by vasoconstriction in the outer cortex associated with acute renal failure and, as such, fits into the general phenomenon of acute renal failure associated with underperfusion of the outer cortex. There is no evidence that underperfusion of the outer cortex is due to a hyperreactivity of special vessels with a different structure from the other vessels supplying this area. There is the fact, however, that the outer cortical vessels are highly reactive to stimuli of many kinds besides angiotensin. Certain unexplained features of acute renal failure in general may be reasonably explained by reference to the effects of underperfusion of the outer cortex. Acute renal failure associated with mild signs of tubule necrosis, for example, may be explained by the fact that although there is afferent underperfusion of the outer cortex there is generally maintained a good venular collateral nutrient supply (maintained capacitance) sufficient for the oxygen requirements of tubules which are not pumping sodium because there is no outer glomerular perfusion or filtration. The significance of the nephrogram in acute renal failure is discussed and explained on the basis of lack of outer cortical glomerular perfusion with adequate perfusion of inner cortical glomeruli. Although, normally, the kidney is perfused by an unusually large volume of blood the proportion of outer cortical perfusion determines the function of the kidney rather than total renal blood flow, oxygen consumption, A-V O2 differences and rate of transit time.