Acute decrease in renal microvascular PO2 during acute normovolemic hemodilution.
ABSTRACT Large differences in the tolerance of organ systems to conditions of decreased O(2) delivery such as hemodilution exist. The kidney receives approximately 25% of the cardiac output and O(2) delivery is in excess of the oxygen demand under normal circumstances. In a rat model of acute normovolemic hemodilution (ANH), we studied the effect of reduced hematocrit on renal regional and microvascular oxygenation. Experiments were performed in 12 anesthetized male Wistar rats. Six animals underwent four steps of ANH (hematocrit 25, 15, 10, and <10%). Six animals served as time-matched controls. Systemic and renal hemodynamic and oxygenation parameters were monitored. Renal cortical (c) and outer medullary (m) microvascular PO(2) (microPO(2)) and the renal venous PO(2) (P(rv)O(2)) were continuously measured by oxygen-dependent quenching of phosphorescence. Despite a significant increase in renal blood flow in the first two steps of ANH, cmicroPO(2) and mmicroPO(2) dropped immediately. From the first step onward oxygen consumption (VO(2(ren))) became dependent on oxygen delivery (DO(2(ren))). With a progressive decrease in hematocrit, a significant correlation between microPO(2) and VO(2(ren)) could be observed, as well as a PO(2) gap between microPO(2) and P(rv)O(2). Furthermore, there was a high correlation between VO(2(ren)) and RBF over a wide range of flows. In conclusion, the oxygen supply to the renal tissue is becoming critical already in an early stage of ANH due to the combination of increased VO(2(ren)), decreased DO(2(ren)), and intrarenal O(2) shunt. This has clinical relevance as recent publications reporting that hemodilution during surgery forms a risk factor for postoperative renal dysfunction.
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ABSTRACT: Chronic kidney disease (CKD) is characterized by irreversible pathological processes that result in the development of end-stage renal disease (ESRD). Accumulating evidence has emphasized the important role of chronic hypoxia in the tubulointerstitium in the final common pathway that leads to development of ESRD. The causes of chronic hypoxia in the tubulointerstitium are multifactorial and include mechanisms such as hemodynamic changes and disturbed oxygen metabolism of resident kidney cells. Epidemiological studies have revealed an association between CKD and systemically hypoxic conditions, such as chronic obstructive pulmonary disease and sleep apnea syndrome. In addition to tubulointerstitial hypoxia, glomerular hypoxia can occur and is a crucial factor in the development of glomerular disorders. Chemical compounds, polarographic sensors, and radiographical methods can be used to detect hypoxia. Therapeutic approaches that target chronic hypoxia in the kidney should be effective against a broad range of kidney diseases. Amelioration of hypoxia is one mechanism of inhibiting the renin-angiotensin system, the current gold standard of CKD therapy. Future therapeutic approaches include protection of the vascular endothelium and appropriate activation of hypoxia-inducible factor, a key transcription factor involved in adaptive responses against hypoxia.Nature Reviews Nephrology 09/2010; 6(11):667-78. · 7.94 Impact Factor
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ABSTRACT: Because of disturbed renal autoregulation, patients experiencing hypotension-induced renal insult might need higher levels of mean arterial pressure (MAP) than the 65 mmHg recommended level in order to avoid the progression of acute kidney insufficiency (AKI). In 217 patients with sustained hypotension, enrolled and followed prospectively, we compared the evolution of the mean arterial pressure (MAP) during the first 24 hours between patients who will show AKI 72 hours after inclusion (AKIh72) and patients who will not. AKIh72 was defined as the need of renal replacement therapy or "Injury" or "Failure" classes of the 5-stage RIFLE classification (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) for acute kidney insufficiency using the creatinine and urine output criteria. This comparison was performed in four different subgroups of patients according to the presence or not of AKI at the sixth hour after inclusion (AKIh6 as defined as a serum creatinine level above 1.5 times baseline value within the first six hours) and the presence or not of septic shock at inclusion.The ability of MAP averaged over H6 to H24 to predict AKIh72 was assessed by the area under the receiver operating characteristic curve (AUC) and compared between groups. The MAP averaged over H6 to H24 or over H12 to H24 was significantly lower in patients who showed AKIh72 than in those who did not, only in septic shock patients with AKIh6, whereas no link was found between MAP and AKIh72 in the three others subgroups of patients. In patients with septic shock plus AKIh6, MAP averaged over H6 to H24 or over H12 to H24 had an AUC of 0.83 (0.72 to 0.92) or 0.84 (0.72 to 0.92), respectively, to predict AKIh72 . In these patients, the best level of MAP to prevent AKIh72 was between 72 and 82 mmHg. MAP about 72 to 82 mmHg could be necessary to avoid acute kidney insufficiency in patients with septic shock and initial renal function impairment.Critical care (London, England) 06/2011; 15(3):R135. · 4.72 Impact Factor
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ABSTRACT: : Acute kidney injury (AKI) is a serious complication of cardiac surgery, and preoperative anemia and perioperative erythrocyte transfusion are important risk factors. Prophylactic erythrocyte transfusion in anemic patients may, therefore, protect against AKI. : In this unblinded, parallel-group, randomized pilot trial, 60 anemic patients (hemoglobin 10-12 g/dL) undergoing cardiac surgery with cardiopulmonary bypass were randomized (1:1) to prophylactic transfusion (2 units of erythrocytes transfused 1 to 2 days before surgery (n = 29) or standard of care (transfusions as indicated; n = 31). Between-group differences in severity of perioperative anemia, transfusion, and AKI (more than 25% drop in estimated glomerular filtration rate) were measured. The relationships between transfusion, iron levels, and AKI were also measured. : Perioperative anemia and erythrocyte transfusions were lower in the prophylactic transfusion group--median (25th, 75th percentiles) for nadir hemoglobin was 8.3 (7.9, 9.1) versus 7.6 (6.9, 8.2) g/dL (P = 0.0008) and for transfusion was 0 (0, 2) versus 2 (1, 4) units (P = 0.0002)--but between-group AKI rates were comparable (11 patients per group). In 35 patients with iron studies, perioperative transfusions were directly related to postoperative transferrin saturation (correlation coefficient 0.6; P = 0.0002), and high (more than 80%) transferrin saturation was associated with AKI (5/5 vs. 8/30; P = 0.005), implicating transfusion-related iron overload as a cause of AKI. : In anemic patients, prophylactic erythrocyte transfusion reduces perioperative anemia and erythrocyte transfusions, and may reduce plasma iron levels. Adequately powered studies assessing the effect of this intervention on AKI are warranted.Anesthesiology 03/2012; 116(3):613-21. · 5.16 Impact Factor