Abstract 41: Changes In Renal Oxygen Consumption With High-salt Diet Differ Between Sprague Dawley And Dahl Salt Sensitive Rats.

It has appeared evident that blood flow to the renal cortex which is required for glomerular filtration far exceeds the delivery of O 2 required for tubular metabolic needs. Yet, the metabolic needs of kidneys are second only to the heart per gram tissue and changes in O 2 extraction and utilization have not been directly measured in face of enhanced workloads such those imposed by high salt (HS) diets. We have developed techniques enabling continuous 24 hr/d monitoring of renal blood flow (RBF; Transonic flow probe) together with blood pressure (BP, 24hr/d) and intermittent sampling of arterial and renal venous blood over 21 days. O 2 content (mL/dL) was determined as 1.31 х Hemoglobin (Hb) (g/dL) х HbO 2 (%) + 0.003 х PaO 2 (mmHg); O 2 consumption (ml/min) was determined as RBF (ml/min) х (arterial-renal venous O 2 content difference). Sprague Dawley rats (SD; n=7; 10 wk age) were compared to Dahl salt-sensitive (SS; n=6; 8 wk age) rats fed 0.4% NaCl and during the 21 days of 4.0% NaCl (HS) diet. Beginning 7 days following surgery, RBF and BP were recorded 24 hr/day, and arterial and renal venous blood sampled for determination of blood gases (ABL800 FLEX radiometer) at 7, 14 and 21 of the HS diet. Average 24 hr mean BP of SD rats increased with the HS diet from 111±2 to 119±5 mmHg and SS rats rose from 121±5 to 155±9 mmHg (p<0.05); average 24 hr RBF of SD rats rose from 9.2±0.6 to 11.7 + 0.6 ml/min (p<0.05) while SS rats exhibited little change (7.0±0.6 to 7.0 + 0.9). RBF when expressed per gram kidney weight (gkw; determined in separate groups of rats) remained unchanged in both SD and SS rats in response to the HS diet. SS rats exhibited lower levels of RBF gkw than SD rats (p<0.05). Expressed either as absolute values or gkw, O 2 extraction and consumption was increased significantly in SD rats but not SS rats fed the HS diet. The results of the study indicate that despite high levels of RBF per tissue weight, increased metabolic work imposed by a HS diet resulted in a significant increase of RBF, O 2 extraction and consumption in normal rats. In contrast, SS rats exhibited lower levels of RBF but failed to increase either O 2 delivery or extraction. This failure may contribute importantly to altered metabolic substrate utilization in SS rats fed a HS diet, progression of ischemic related injury and hypertension.

Renal hemodynamics, function and oxygenation in critically ill patients and after major surgery

The present review outlines the available data from the work of our group on renal hemodynamics, function and oxygenation in critically ill patients with acute renal dysfunction such as in postoperative acute kidney injury, early clinical septic shock, in patients undergoing cardiac surgery with cardiopulmonary bypass or in patients undergoing liver transplantation. We also provide information on renal hemodynamics, function and oxygenation in patients with chronic renal impairment due to congestive heart failure. This review will argue that the common denominator, for these groups of patients, is that renal oxygenation is impaired in all groups caused by a lower renal oxygen delivery or a pronounced increase in renal oxygen consumption.

Alterations in regional kidney oxygenation during expansion of extracellular fluid volume in conscious healthy sheep

Expansion of extracellular fluid volume with crystalloid solutions is a common medical intervention, but its effects on renal cortical and medullary oxygenation are poorly understood. Therefore, we instrumented sheep under general anesthesia to enable continuous measurement of systemic and renal hemodynamics, global renal oxygen delivery and consumption, and intrarenal tissue perfusion and oxygen tension (Po2) in conscious animals ( n = 7). The effects of three sequential intermittent infusions of 500 ml of compound sodium lactate solution, administered at hourly intervals, were determined. Volume expansion induced transient increases in mean arterial pressure (+7 ± 2%), central venous pressure (+50 ± 19%), and cardiac output (+15 ± 3%). There were sustained increases in renal medullary tissue Po2 (+35 ± 10%) despite increases in global renal oxygen consumption (+66 ± 18%) and renal oxygen extraction (+64 ± 8%). Volume expansion did not significantly alter renal blood flow, renal oxygen delivery, or medullary perfusion. The sustained increase in medullary Po2 was paralleled by increased bladder urine Po2 (34 ± 4%). Cortical perfusion and Po2 did not change significantly. Our findings indicate that extracellular fluid volume expansion can increase renal medullary oxygenation, providing a potential mechanistic basis for its use as prophylaxis against iatrogenic acute kidney injury. They also indicate that continuous measurement of bladder urine Po2 could be used to monitor the effects of volume expansion on medullary oxygenation. However, the mechanisms mediating increased medullary oxygenation during volume expansion remain to be determined.

Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated hemorrhage

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and hemorrhage. We found that losartan does not cause renal cortical hypoxia after hemorrhage in rats because of decreased renal vascular resistance, but we did not evaluate resuscitation. We aimed to study losartan’s effect on renal cortical and medullary oxygenation, as well as norepinephrine’s vasopressor effect in a model of resuscitated hemorrhage. After 7 days of losartan (60 mg·kg−1·day−1) or control treatment, male Wistar rats were hemorrhaged 20% of their blood volume and resuscitated with Ringerʼs acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation were measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated hemorrhage. A smaller increase of renal vascular resistance in the losartan group translated to a smaller decrease in cortical oxygen tension, but no significant difference was seen in medullary oxygen tension, either between groups or after hemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in control- and losartan-treated rats. Losartan does not decrease renal oxygenation after resuscitated hemorrhage because of a smaller increase in renal vascular resistance. Further, losartan does not decrease the efficiency of norepinephrine as a vasopressor, indicating that blood pressure may be managed effectively during losartan treatment.

Accounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia

We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension ([Formula: see text]) or microvascular oxygen tension (µPo2) were within ±1 SE of the mean value observed experimentally. The predicted [Formula: see text] or µPo2 in response to ischemia-reperfusion injury, acute hemodilution, blockade of nitric oxide synthase, or uncoupling mitochondrial respiration, were within ±2 SE observed experimentally. We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted [Formula: see text] and µPo2. The model parameters analyzed were as follows: 1) the major determinants of renal oxygen delivery ([Formula: see text]) (arterial blood Po2, hemoglobin concentration, and renal blood flow); 2) the major determinants of renal oxygen consumption (V̇o2) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (β)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of [Formula: see text] and µPo2 to the major the determinants of [Formula: see text] and V̇o2. The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease.

Adaptive changes in GFR, tubular morphology, and transport in subtotal nephrectomized kidneys: modeling and analysis

Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevations in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat. Model simulations indicate that nephrectomy-induced SNGFR increase and tubular hypertrophy go a long way to normalize excretion, but alone are insufficient to fully maintain salt balance. We then identified increases in the protein density of Na+-K+-ATPase, Na+-K+-2Cl− cotransporter, Na+-Cl− cotransporter, and epithelial Na+ channel, such that the UNX and 5/6-NX models predict urine flow and urinary Na+ and K+ excretions that are similar to sham levels. The models predict that, in the UNX and 5/6-NX kidneys, fractional water and salt reabsorption is similar to sham along the initial nephron segments (i.e., from the proximal tubule to the distal convoluted tubule), with a need to further reduce Na+ reabsorption and increase K+ secretion primarily along the connecting tubules and collecting ducts to achieve balance. Additionally, the models predict that, given the substantially elevated filtered and thus transport load among each of the surviving nephrons, oxygen consumption per nephron segment in a UNX or 5/6-NX kidney increases substantially. But due to the reduced nephron population, whole animal renal oxygen consumption is lower. The efficiency of tubular Na+ transport in the UNX and 5/6-NX kidneys is predicted to be similar to sham.