Effect of hemorrhagic reduction in blood pressure on recovery from acute renal failure

Abstract

The effect of hemorrhagic reduction in systemic blood pressure (SBP) to 90 mm Hg for four hours on autoregulation of renal blood flow (RBF), renal function, and renal histology was examined in control rats, one week norepinephrine-induced acute renal failure (NE-ARF) rats with intact renal nerves, and one week NE-ARF rats with prior renal denervation. The results showed that in control rats, hemorrhagic SBP reduction to 90 mm Hg had no effect on autoregulation of RBF (autoregulatory index = 0.09 +/- 0.02), creatinine clearance, or renal histology. However, in one week NE-ARF rats with intact renal nerves, hemorrhagic reduction in SBP to 90 mm Hg was associated with marked impairment of autoregulation of RBF (autoregulatory index = 3.49 +/- 0.25), further reduction in creatinine clearance from 0.59 +/- 0.08 ml/min to 0.36 +/- 0.14 ml/min, and histologic evidence of recurrent ischemic injury. Renal denervation prior to SBP reduction improved autoregulation of RBF (autoregulatory index = 0.30 +/- 0.09), prevented the further reduction in creatinine clearance, and significantly ameliorated the deleterious effect on renal histology seen in innervated NE-ARF rats. These results suggest the potential importance of the loss of autoregulation of RBF on the course of NE-ARF, and further support the pathogenetic role of renal nerves in the loss of autoregulation.

Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure.

“…Indeed, the documentation that fresh tubular necrosis may be observed as late as 4 wk after the onset of ARF in patients (11) is compatible with this possibility. Moreover, the observation that in 7-d NE-induced ARF rats a lowering of RPP within the autoregulatory range is associated with tubular necrosis and the worsening of azotemia, while no detectable changes occur in normal rats, also supports this possibility (12). Since intracellular calcium is known to be an important mediator ofvascular contractility (14), and CEBs are known to attenuate experimental ARF in animals (22) as well as enhance cadaver graft survival in patients (23), the possibility exists that some ofthe vascular abnormalities in ischemic ARF may be modulated by perturbations in cell calcium.…”

“…Thus, subclinical ischemic episodes may cause tubular necrosis in a kidney recovering from ARF because of a renal vasoconstriction to relatively small reductions in RPP, hypersensitivity to RNS, and loss of renal vasodilatory influences. Support for this possibility has been reported recently in the rat where transient reduction in mean RPP from 120 to 90 mmHg caused recurrent azotemia and fresh areas of necrosis in ARF rats (12).…”

Angiotensin and thromboxane in the enhanced renal adrenergic nerve sensitivity of acute renal failure.

“…A potential role for accelerated renal adrenergic nerve activity in recurrent ischemic injury in the maintenance phase of NE-ARF was supported by experiments in which renal denervation was carried out before transient reduction in RPP. Unlike rats with intact renal nerves, those with renal denervation had neither recurrent increases in blood urea nitrogen or serum creatinine nor new ischemic lesions in the kidneys (22). These data appeared to implicate enhanced response to adrenergic nerve impulses in the abnormal vascular sensitivity to RPP manipulation in established ischemic ARF.…”

Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

“…For example, patients who have more severe or persistent AKD 11,96 , those with premorbid conditions that increase the risk of future CKD progression (for example, those with evidence of pre-existing CKD, diabetes and/or proteinuria), and those with recurrent disease or non-recovery (for example, those with congestive heart failure, cirrhosis, and/or malignancy with or without chemotherapy) might achieve greater benefit from earlier or more frequent surveillance than patients with a lower risk of future CKD 97,98 . This hypothesis is supported by data showing that rates of re-hospitalization and recurrent AKI are high among patients with similar risk factors 95,[98][99][100][101][102][103][104] .…”