Redistribution Of Intrarenal Blood Flow Research Articles

Causes and management of urinary system problems in children on long-term home invasive mechanical ventilation.

Many ventilator-dependent children have comorbid conditions including urinary tract disorders. We aimed to present a focused review of the literature describing the causes and management of urinary system problems in children with long-term home mechanical ventilation. We performed a literature search in PubMed/MEDLINE, Scopus, and Web of Science with keywords "children," "home mechanical ventilation," "urinary system," "urinary tract," "neurogenic bladder," "clean intermittent catheterization," "urinary tract infection," "urolithiasis," and "acute kidney injury." We included original articles, reviews, guidelines, and case reports published in English. Ventilator-dependent children may have neurogenic bladder/bowel dysfunction which renders them prone to urinary tract infection, high bladder pressure, vesicoureteral reflux, hydronephrosis, and renal dysfunction. These children require bladder catheterization, medications affecting parasympathetic/sympathetic nervous systems, or surgical procedures to prevent urinary infections, and to maintain continence and renal functions. However, bladder catheterization or surgical procedures like augmentation cystoplasty may also be complicated with urinary infections, urolithiasis, or urethral strictures. Urolithiasis frequency is also increased due to immobilization-related hypercalciuria, hypocitraturia caused by antiepileptic drugs, urinary stasis, and urinary infections. On the other hand, mechanical ventilation can impair renal function by reduction of cardiac output, redistribution of intrarenal blood flow and stimulation of sympathetic and hormonal pathways. Children requiring long-term invasive home mechanical ventilation may have other comorbid conditions, including urinary system diseases, which become manifest as these patients are being kept alive due to the advances in ventilation strategies. These children must be carefully observed for urological complications and managed accordingly to prevent kidney injury.

Re: Effect of Alprostadil in the Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of 36 Randomized Controlled Trials

Contrast-induced nephropathy (CIN) is the third leading cause of acquired acute renal injury in hospitalized patients. Alprostadil plays a role in the maintenance and redistribution of intrarenal blood flow and the excretion of electrolytes and water. However, the effectiveness of alprostadil in preventing CIN remains controversial. Thirty-six articles with a total of 5495 patients were included in this study. Both groups (experimental group and control group) received standard hydration therapy. In the experimental group, patients received different doses of alprostadil. Serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), cystatin C, creatinine clearance rate (CCr), and β2-microglobulin (β2-MG) were measured at 24, 48, and 72 hours after contrast media injection. The incidence of CIN in the experimental group was significantly lower than that in the control group (6.56% vs 16.74%). The level of SCr, cystatin C, BUN, and β2-MG in the experimental group was lower than those in the control group; CCr and eGFR in the experimental group were higher than those in the control group. This study demonstrated that alprostadil may reduce the incidence of CIN in patients undergoing coronary angiogram and/or percutaneous coronary intervention.

Effect of Alprostadil on the Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of 36 Randomized Controlled Trials.

Contrast-induced nephropathy (CIN) is the third leading cause of acquired acute renal injury in hospitalized patients. Alprostadil plays a role in the maintenance and redistribution of intrarenal blood flow and the excretion of electrolytes and water. However, the effectiveness of alprostadil in preventing CIN remains controversial. Thirty-six articles with a total of 5495 patients were included in this study. Both groups (experimental group and control group) received standard hydration therapy. In the experimental group, patients received different doses of alprostadil. Serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), cystatin C, creatinine clearance rate (CCr), and β2-microglobulin (β2-MG) were measured at 24, 48, and 72 hours after contrast media injection. The incidence of CIN in the experimental group was significantly lower than that in the control group (6.56% vs 16.74%). The level of SCr, cystatin C, BUN, and β2-MG in the experimental group was lower than those in the control group; CCr and eGFR in the experimental group were higher than those in the control group. This study demonstrated that alprostadil may reduce the incidence of CIN in patients undergoing coronary angiogram and/or percutaneous coronary intervention.

An Ovine Model for Studying the Pathophysiology of Septic Acute Kidney Injury.

The development of acute kidney injury (AKI) is both a significant and independent prognostic factor of mortality in patients with sepsis, but its pathophysiology remains unclear. Herein, we describe an ovine model of sepsis evoked by the administration of live Escherichia coli in which there is hypotension, peripheral vasodilatation with a large increase in cardiac output; a similar hyperdynamic state to that commonly reported in humans. Interestingly, in this sheep model of sepsis, despite an increase in global kidney blood flow, there is a progressive reduction in renal function. Although renal hyperperfusion develops, renal tissue hypoxia due to redistribution of intrarenal blood flow may contribute to the pathogenesis of septic AKI. We have, therefore, developed a novel methodology to chronically implant combination probes to monitor intrarenal tissue perfusion and oxygen tension during the development of septic AKI in conscious sheep with hyperdynamic sepsis.

Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury

Norepinephrine is the principal vasopressor used to restore blood pressure in sepsis, but its effects on intrarenal oxygenation are unknown. To clarify this, we examined renal cortical, medullary, and urinary oxygenation in ovine septic acute kidney injury and the response to resuscitation with norepinephrine. A renal artery flow probe and fiberoptic probes were placed in the cortex and medulla of sheep to measure tissue perfusion and oxygenation. A probe in the bladder catheter measured urinary oxygenation. Sepsis was induced in conscious sheep by infusion of Escherichia coli for 32 hours. At 24 to 30 hours of sepsis, either norepinephrine, to restore mean arterial pressure to preseptic levels or vehicle-saline was infused (8 sheep per group). Septic acute kidney injury was characterized by a reduction in blood pressure of ∼12 mmHg, renal hyperperfusion, and oliguria. Sepsis reduced medullary perfusion (from an average of 1289 to 628 blood perfusion units), medullary oxygenation (from 32 to 16 mmHg), and urinary oxygenation (from 36 to 24 mmHg). Restoring blood pressure with norepinephrine further reduced medullary perfusion to an average of 331 blood perfusion units, medullary oxygenation to 8mmHg and urinary oxygenation to 18 mmHg. Cortical perfusion and oxygenation were preserved. Thus, renal medullary hypoxia caused by intrarenal blood flow redistribution may contribute to the development of septic acute kidney injury, and resuscitation of blood pressure with norepinephrine exacerbates medullary hypoxia. The parallel changes in medullary and urinary oxygenation suggest that urinary oxygenation may be a useful real-time biomarker for risk of acute kidney injury.

Cortical and Medullary Tissue Perfusion and Oxygenation in Experimental Septic Acute Kidney Injury.

To determine whether there is a decrease in renal cortical or medullary perfusion and oxygenation in a conscious large animal model of hyperdynamic septic shock with acute kidney injury. Interventional animal study. University-affiliated research institute. Eight merino ewes. Sheep were surgically instrumented with pulmonary and renal artery flow probes in the renal cortex and medulla, combination fiber-optic probes comprising a fluorescence optode to measure tissue PO2, and a laser-Doppler probe to assess tissue perfusion. Sepsis was induced by infusion of live Escherichia coli for 24 hours followed by 24-hour recovery. In unanesthetized normal sheep, resting levels of cortical and medullary tissue PO2 were 29.5 ± 4.4 and 29.1 ± 4.3 mm Hg, respectively. During infusion of E. coli, hyperdynamic sepsis developed with hypotension, tachycardia, increased cardiac output, increased renal blood flow, oliguria, decreased creatinine clearance, and increased serum creatinine. Renal oxygen delivery increased while renal oxygen consumption was unchanged. During sepsis, cortical tissue PO2 increased from 29.4 ± 4.3 to 36.3 ± 3.5 mm Hg (p < 0.001), whereas medullary oxygenation decreased from 29.6 ± 4.7 to 13.1 ± 2.7 mm Hg (p < 0.001). Cortical perfusion was not significantly changed, but medullary perfusion decreased (671 BPU [500-900 BPU] to 480 BPU [349-661 BPU]; geometric mean [95% CI]; p < 0.001). In a large animal model of hyperdynamic sepsis, renal hyperemia was associated with preserved cortical oxygenation and perfusion, but decreased medullary oxygenation and perfusion. Medullary hypoxia due to intrarenal blood flow redistribution may be one of the factors causing acute kidney injury in sepsis.

Renal Blood Flow Redistribution During Acute Kidney Injury

We describe a case of acute kidney injury with decreased kidney perfusion in which contrast-enhanced computed tomography of the abdomen was performed for a nonrenal indication. This imaging procedure showed intrarenal blood flow redistribution from the cortex to the medulla that reversed after recovery of kidney function. Renal blood flow redistribution was described first almost a century ago in experimental models of renal ischemia, but clinical imaging studies are scarce. We provide a clear example of this phenomenon using contrast-enhanced computed tomography.

Nitric Oxide Mediates Redistribution of Intrarenal Blood Flow during Bacteremia

The normal or hyperdynamic circulatory response during the early phases of the systemic septic response is associated with renal microvascular constriction and can result in renal dysfunction. Intrarenal redistribution of blood flow from the outer cortex to the medulla appears to account for decreased glomerular filtration in spite of normal or elevated renal blood flow, but the mechanisms of this response are not well described. Nitric oxide is recognized as an important regulator of regional blood flow during both normal and pathologic conditions including sepsis, and we hypothesized that alterations in nitric oxide contribute to redistribution of renal blood flow during sepsis. The current study used laser Doppler fluximetry and clearance of p-aminohippuric acid (effective renal plasma flow, ERPF) to study intrarenal distribution of blood flow during basal conditions and during normodynamic Escherichia coli bacteremia, with and without inhibition of nitric oxide. Inhibition of nitric oxide in normal animals resulted in a decrease in ERPF (-19%) with a decrease in cortical flux (-39%) without alteration of medullary flux. Bacteremia resulted in a decrease in cortical flow (-17%), an increase in medullary flow (36%), and a modest reduction (-9%) in ERPF. Inhibition of nitric oxide synthase during bacteremia worsened cortical flow (-43%), reversed the increase in medullary flux (-42%), and further impaired ERPF (-28%). These data suggest that nitric oxide regulates renovascular tone during normal conditions and bacteremia, and indicate that it is a prime mediator of intrarenal redistribution of blood flow during sepsis.

Distribution of systemic blood flow in lambs with an aortopulmonary shunt during strenuous exercise.

We studied regional blood flows with radioactive-labeled microspheres in 12 7-wk-old lambs with an aortopulmonary left-to-right shunt [59 +/- 3% (SE) of left ventricular (LV) output] and in 11 control lambs, at rest and during exercise at 80% of predetermined peak O2 consumption. At rest, systemic blood flow was similar in the two groups. Blood flow to the heart and diaphragm was substantially higher in the shunt than in the control lambs. Blood flow to the other organs was not significantly different between the two groups. During exercise, systemic blood flow increased substantially but less in shunt (81%) than in control lambs (134%). Blood flow to the heart and diaphragm increased, that to the heart still being higher in shunt than in control lambs. Blood flow to the brain did not change, whereas that to the kidneys and splanchnic organs decreased to the same extent (25%) in shunt and control lambs. Intrahepatic and intrarenal blood flow redistribution in the shunt lambs persisted during exercise. In conclusion, myocardial blood flow is not increased at the expense of one particular organ, nor is it associated with an essential change in exercise-induced redistribution in shunt lambs.

Effect of partial nephrectomy on mercuric chloride-induced acute renal failure

We investigated the effect of partial nephrectomy on mercuric chloride (HgCl2)-induced acute renal failure (ARF) in rats. HgCl2 (2 mg/kg) was subcutaneously injected to male Wistar rats 2 days or 2 weeks after either partial nephrectomy or sham surgery. Both deterioration of renal function (serum creatinine, creatinine clearance, and fractional excretion of sodium) and renal tubular damage due to HgCl2-induced ARF were inhibited by 5/6 nephrectomy. A moderate inhibitory effect was also noted by uninephrectomy. The levels of renal tissue ATP and total nucleotide did not increase 12 and 48 hours after uninephrectomy. These results suggest that partial nephrectomy is effective in suppressing the development of HgCl2-induced ARF. The mechanisms of the protection are not explained completely by a consequence of hypertrophy or an acceleration of intracellular energy metabolism. Intrarenal blood flow redistribution may be involved in one of the mechanisms.

Redistribution of renal blood flow in patients with liver cirrhosis: The role of renal PGE 2

Cirrhotic patients frequently show a decrease in renal blood flow and redistribution of the flow from the outer cortex to the juxtamedullary cortex. The cause of the maintenance of juxtamedullary perfusion is not presently known. Prostaglandin E2 (PGE2) has its vasodilating effect on medullary and juxtamedullary vessels where it is synthesized. Therefore, its increased production, frequently shown in cirrhotics, could be responsible for the relative preservation of juxtamedullary blood flow. To verify this hypothesis we examined 13 cirrhotic patients. In these patients we determined mean renal blood flow (MRBF), blood flow in the 1st compartment (ICBF) and in the 2nd compartment (IICBF) with the 133-Xenon washout technique and PGE2 plasma levels in the renal veins (PGE2V). MRBF and ICBF were significantly reduced as compared to control subjects (P less than 0.01); IICBF resulted unaltered. Significant correlation was found between IICBF and PGE2V (P less than 0.01). Our data confirm the decrease in renal blood flow and the redistribution of intrarenal blood flow in cirrhotic patients. The maintenance of IICBF is likely to be a consequence of PGE2 renal production.

Redistribution of intra-renal blood flow (IRBF) by atriopeptin-II (r-ANF), theophylline or furosemide in the cat

Redistribution of intra-renal blood flow (IRBF) by atriopeptin-II (r-ANF), theophylline or furosemide in the cat

Redistribution of intrarenal blood flow after carotid artery occlusion in the rat.

As indicated by changes in microsphere distribution in the rat, acute bilateral carotid artery occlusion (CAO) was found to cause a small but significant increase in outer cortical flow fraction. When renal perfusion pressure was kept constant, no redistribution occurred upon CAO. In denervated kidneys the redistribution induced by CAO did not differ from that observed in contralateral control kidneys. Animals pretreated with prostaglandin inhibitors showed a significant redistribution in the 'unprotected' right kidney and a minor increase in outer cortical flow fraction in the normotensive kidney. It is concluded that: (1) the increase in outer cortical flow fraction induced by CAO in the rat is due to an increase in perfusion pressure, and (2) that this redistribution is independent of sympathetic vasoconstrictor stimuli, catecholamines and prostaglandins.

Renal handling of salt and water in the early stage of obstructive jaundice in rabbits.

Renal handling of salt and water in the early stage of obstructive jaundice was studied in rabbits 10 days after the ligation of the common bile duct (BDL). Sham-operated (SO) animals served as controls. No sodium retention was found in BDL rabbits, despite reduced renal perfusion and elevated plasma aldosterone level. A redistribution of intrarenal blood flow was not found. The filtration fraction did not change. A saline load resulted in decreases in arterial hematocrit and total serum proteins, and increases in urine output, urinary sodium excretion and osmolal clearance. Blood pressure, glomerular filtration rate (GFR), RPF, the filtration fraction and the intrarenal flow distribution were not significantly affected by the saline load. No significant difference was found in the natriuretic response to the saline load between the BDL and SO groups. After 60 h of water deprivation, there was no significant difference in urine-to-plasma osmolality ratios or renal tissue fluid osmolality between the BDL and SO animals. The findings indicate that renal handling of salt and water was well maintained in the early phase of obstructive jaundice in rabbits. The data also suggest the critical role of the redistribution of intrarenal blood flow rather than of GFR or aldosterone in determining sodium retention in obstructive jaundice.

The role of renal metabolism of PGE 2 in determining its activity as a renal vasodilator in the dog

Since the mammalian renal cortex avidly metabolizes prostaglandin E 2 (PGE 2), we examined the importance of renal metabolism of PGE 2 in determining its renal vascular activity in the dog. We used 13, 14 dihydro PGE 2 (DHPGE 2) as a model compound to study this because DHPGE 2 retains similar activity to the parent prostaglandin, PGE 2, but is a poorer substrate than PGE 2 for both the metabolism and the cellular uptake of the prostaglandins. Using dog renal cortical slices, we found that under similar experimental conditions, PGE 2 was metabolized several-fold faster than DHPGE 2. Both prostaglandins were metabolized to the 15 keto 13, 14 dihydro PGE 2, which was positively identified using GC-MS. In vivo, we infused increasing concentrations of DHPGE 2 into the renal artery of dogs and measured renal hemodynamic changes using radioactive microspheres. DHPGE 2 was a potent renal vasodilator beginning at an infusion rate of 10 −9g/kg/min. When compared to PGE 2, DHPGE 2 was about 10 times more potent in affecting renal vasodilation. The intrarenal redistribution of blood flow towards the inner cortex seen with DHPGE 2 was identical to that seen with PGE 2. We conclude that renal catabolism of PGE 2 is very important in limiting the in vivo biological activity of PGE 2, but regional differences in metabolism of PGE 2 within the cortex are an unlikely determinant of the pattern of redistribution of renal blood flow.

Redistribution of intrarenal blood flow following adh administration: Lack of inhibition by blockade of prostaglandin cyclooxygenase

The effect of prostaglandin synthesis inhibition on the redistribution of renal cortical blood flow in response to antidiuretic hormone (ADH) was examined using radioactive microspheres in water loaded, thiopental-anesthetized dogs. Microsphere injections were made during a control and an ADH infusion period (0.35 mU/kg/min following a 20 mU/kg bolus) both before and after indomethacin pretreatment (8 mg/kg intravenously). Urinary prostaglandin E 2 (PGE 2) excretion in each period was measured by gas chromatography-mass spectrometry. ADH caused a marked redistribution of flow toward inner cortical zones from 19±1 to 25±2 ml/min (mean ± SE, p < 0.01). Fractional flow to inner zones was also significantly increased. Indomethacin pretreatment had no effect on the ADH-induced redistribution (17±2 vs. 24±2 ml/min, p < 0.01), although urinary PGE 2 excretion was suppressed by indomethacin by 60%. It is concluded that prostaglandins do not mediate the redistribution of intrarenal blood flow accompanying ADH administration.

Effect of indomethacin on renal function in anaesthetized dogs.

The inhibitory action of indomethacin administered as a single-dose injection (4mg/kg) was examined under general anaesthesia in dogs, moderate volume expansion having been induced with physiological saline infusion. At 20 to 30 min after the administration of indomethacin, excretion of Na and water showed a fall of the same extent, GFR remaining stable and the effective plasma flow (CPAH) declining. RBF estimated by the 86Rb method decreased from 411 +/- 96 ml/min/100 g to 292 +/- 53 ml/min/100 g (p less than 0.01). This fall was coupled with an intrarenal redistribution of blood flow. While the cortical fraction of renal blood flow increased from 79% to 83.9% (p less than 0.001), its outer medullary fraction decreased from 17% to 13.2% (p less than 0.001) and its inner medullary fraction from 4.0% to 2.8% (p less than 0.05). The renal, primarily the medullary, vasculature is assumed on these grounds to be under the influence of a continuous secretion of prostaglandins which thus seem to be involved in the physiological control of intrarenal distribution of blood flow and of sodium and water excretion.

Mechanism of intrarenal blood flow redistribution after carotid artery occlusion.

Bilateral carotid artery occlusion results in an increase in mean arterial pressure, an increase in renal sympathetic nerve activity, and a redistribution of renal blood flow from inner to outer cortex. To elucidate the mechanism of the renal blood flow redistribution, carotid artery occlusion was performed in anesthetized dogs with the left kidney either having renal perfusion pressure maintained constant (aortic constriction) or having alpha-adrenergic receptor blockade (phenoxybenzamine); the right kidney of the same dog served to document the normal response. When renal perfusion pressure was maintained constant, renal blood flow distribution (microspheres) was unchanged by carotid artery occlusion. In the presence of renal alpha-adrenergic receptor blockade, carotid artery occlusion elicited the usual redistribution of renal blood flow from inner to outer cortex. The redistribution of renal blood flow observed after carotid artery occlusion is mediated by the increase in renal perfusion pressure rather than the increase in renal sympathetic nerve activity.

Renal blood flow during ureteral obstruction measured with 133Xe wash out, 86Rb uptake techniques and with an electromagnetic flowmeter.

In moderate mannitol diuresis in the dog the ratio RBF-86Rb uptake/RBF-electromagnetic flowmeter decreased during ureteral obstruction from 0.923 - 0.705. In the same animals the ratio RBF-133Xe wash-out/RBF-electromagnetic flowmeter increased from 0.932 - 1.365. With the rubidium technique a significant redistribution of intrarenal blood flow was observed. No similar flow changes were seen with the 133Xe wash-out technique. The two methods do not measure during ureteral obstruction the true RBF. The change of 86Rb uptake by the individual segments of renal tissue is not an unequivocal proof for the intrarenal redistribution of blood flow, but this possibility cannot be definitely excluded.

Effects of positive pressure ventilation on intrarenal blood flow in infant primates.

Extract: Measurement of intrarenal distribution of renal blood flow by injection of radionuclides in 3—5-day-old infant monkeys showed a preponderance of outer cortical over inner cortical flow with flow rates of 4.23 and 2.54 ml/min/g, respectively. Intermittent positive pressure ventilation (IPPV) causes a reversal of this flow pattern. The theoretical difference in nephron function in these two areas suggests that this reversal in intrarenal flow induced by IPPV may have important clinical implications. Speculation: Extrarenal stimuli such as IPPV causes a redistribution of intrarenal blood flow in infant primates. Any stimuli that results in increased production of epinephrine or similar compounds may be responsible for this redistribution by a local effect on outer cortical blood vessels. Our data further suggest that antidiuretic hormone may influence intrarenal blood flow in addition to altering tubular membrane permeability.