Gudrun Bragadottir

Acute renal failure is NOT an "acute renal success"--a clinical study on the renal oxygen supply/demand relationship in acute kidney injury.

Objectives:Acute kidney injury occurs frequently after cardiac or major vascular surgery and is believed to be predominantly a consequence of impaired renal oxygenation. However, in patients with acute kidney injury, data on renal oxygen consumption (RVO2), renal blood flow, glomerular filtration, and renal oxygenation, i.e., the renal oxygen supply/demand relationship, are lacking and current views on renal oxygenation in the clinical situation of acute kidney injury are presumptive and largely based on experimental studies. Design:Prospective, two-group comparative study. Setting:Cardiothoracic intensive care unit of a tertiary center. Patients:Postcardiac surgery patients with (n = 12) and without (n = 37) acute kidney injury were compared with respect to renal blood flow, glomerular filtration, RVO2, and renal oxygenation. Interventions:None Measurements and Main Results:Data on systemic hemodynamics (pulmonary artery catheter) and renal variables were obtained during two 30-min periods. Renal blood flow was measured using two independent techniques: the renal vein thermodilution technique and the infusion clearance of paraaminohippuric acid, corrected for renal extraction of paraaminohippuric acid. The filtration fraction was measured by the renal extraction of 51Cr-EDTA and the renal sodium resorption was measured as the difference between filtered and excreted sodium. Renal oxygenation was estimated from the renal oxygen extraction. Cardiac index and mean arterial pressure did not differ between the two groups. In the acute kidney injury group, glomerular filtration (−57%), renal blood flow (−40%), filtration fraction (−26%), and sodium resorption (−59%) were lower, renal vascular resistance (52%) and renal oxygen extraction (68%) were higher, whereas there was no difference in renal oxygen consumption between groups. Renal oxygen consumption for one unit of reabsorbed sodium was 2.4 times higher in acute kidney injury. Conclusions:Renal oxygenation is severely impaired in acute kidney injury after cardiac surgery, despite the decrease in glomerular filtration and tubular workload. This was caused by a combination of renal vasoconstriction and tubular sodium resorption at a high oxygen demand.

Renal oxygenation and haemodynamics in acute kidney injury and chronic kidney disease.

Acute kidney injury (AKI) is a major burden on health systems and may arise from multiple initiating insults, including ischaemia‐reperfusion injury, cardiovascular surgery, radiocontrast administration and sepsis. Similarly, the incidence and prevalence of chronic kidney disease (CKD) continues to increase, with significant morbidity and mortality. Moreover, an increasing number of AKI patients survive to develop CKD and end‐stage renal disease. Although the mechanisms for the development of AKI and progression to CKD remain poorly understood, initial impairment of oxygen balance likely constitutes a common pathway, causing renal tissue hypoxia and ATP starvation that, in turn, induce extracellular matrix production, collagen deposition and fibrosis. Thus, possible future strategies for one or both conditions may involve dopamine, loop diuretics, atrial natriuretic peptide and inhibitors of inducible nitric oxide synthase, substances that target kidney oxygen consumption and regulators of renal oxygenation, such as nitric oxide and heme oxygenase‐1.

Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury - true GFR versus urinary creatinine clearance and estimating equations

IntroductionEstimation of kidney function in critically ill patients with acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but challenging due to fluctuations in kidney function, creatinine metabolism and fluid balance. Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, the Cockcroft Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison to GFR measured by the infusion clearance of chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), in critically ill patients with early AKI after complicated cardiac surgery.MethodsThirty patients with early AKI were studied in the intensive care unit, 2 to 12 days after complicated cardiac surgery. The infusion clearance for 51Cr-EDTA obtained as a measure of GFR (GFR51Cr-EDTA) was calculated from the formula: GFR (mL/min/1.73m2) = (51Cr-EDTA infusion rate × 1.73)/(arterial 51Cr-EDTA × body surface area) and compared with the urinary CrCl and the estimated GFR (eGFR) from the three estimating equations. Urine was collected in two 30-minute periods to measure urine flow and urine creatinine. Urinary CrCl was calculated from the formula: CrCl (mL/min/1.73m2) = (urine volume × urine creatinine × 1.73)/(serum creatinine × 30 min × body surface area).ResultsThe within-group error was lower for GFR51Cr-EDTA than the urinary CrCl method, 7.2% versus 55.0%. The between-method bias was 2.6, 11.6, 11.1 and 7.39 ml/min for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. The error was 103%, 68.7%, 67.7% and 68.0% for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA.ConclusionsThe study demonstrated poor precision of the commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI, suggesting that this should not be used as a reference method when validating new methods for assessing kidney function in this patient population. The commonly used estimating equations perform poorly when estimating GFR, with high biases and unacceptably high errors.

Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study.

Objectives:Acute kidney injury develops in a large proportion of patients after cardiac surgery because of the low cardiac output syndrome. The inodilator levosimendan increases cardiac output after cardiac surgery with cardiopulmonary bypass, but a detailed analysis of its effects on renal perfusion, glomerular filtration, and renal oxygenation in this group of patients is lacking. We therefore evaluated the effects of levosimendan on renal blood flow, glomerular filtration rate, renal oxygen consumption, and renal oxygen demand/supply relationship, i.e., renal oxygen extraction, early after cardiac surgery with cardiopulmonary bypass. Design:Prospective, placebo-controlled, and randomized trial. Setting:Cardiothoracic ICU of a tertiary center. Patients:Postcardiac surgery patients (n = 30). Interventions:The patients were randomized to receive levosimendan, 0.1 µg/kg/min after a loading dose of 12 µg/kg (n = 15), or placebo (n = 15). Measurements and Main Results:The experimental procedure started 4–6 hours after surgery in the ICU during propofol sedation and mechanical ventilation. Systemic hemodynamic were evaluated by a pulmonary artery thermodilution catheter. Renal blood flow and glomerular filtration rate were measured by the renal vein retrograde thermodilution technique and by renal extraction of 51Cr-EDTA, respectively. Central venous pressure was kept constant by colloid/crystalloid infusion. Compared to placebo, levosimendan increased cardiac index (22%), stroke volume index (15%), and heart rate (7%) and decreased systemic vascular resistance index (21%), whereas mean arterial pressure was not affected. Levosimendan induced significant increases in renal blood flow (12%, p < 0.05) and glomerular filtration rate (21%, p < 0.05), decreased renal vascular resistance (18%, p < 0.05) but caused no significant changes in filtration fraction, renal oxygen consumption, or renal oxygen extraction, compared to placebo. Conclusions:After cardiac surgery with cardiopulmonary bypass, levosimendan induces a vasodilation, preferentially of preglomerular resistance vessels, increasing both renal blood flow and glomerular filtration rate without jeopardizing renal oxygenation. Due to its pharmacodynamic profile, levosimendan might be an interesting alternative for treatment of postoperative heart failure complicated by acute kidney injury in postcardiac surgery patients.

Low-dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post-cardiac surgery patients.

Background: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine‐dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and renal oxygen extraction (RO2Ex) in post‐cardiac surgery patients.

Renal oxygenation in clinical acute kidney injury

Renal oxygenation is defined as the relationship between renal oxygen delivery (DO2) and renal oxygen consumption (VO2) and it can easily be shown that the inverse of this relationship is equivalent to renal extraction of O2 (O2Ex). An increase in renal O2Ex means that renal DO2 has decreased in relation to renal VO2, i. e., renal oxygenation is impaired, and vice versa. When compared to other major organs, renal VO2 is relatively high, second only to the heart. In sedated, mechanically ventilated patients, renal VO2 is two-thirds (10 ml/min) that of myocardial oxygen consumption (15 ml/min) (Table 1) [1, 2]. Renal blood flow, which accounts for approximately 20 % of cardiac output, is three times higher than myocardial blood flow in this group of patients. Renal O2Ex in the non-failing kidney is therefore low, 10 %, compared with, e.g., the heart, in which O2EX is 55 % (Table 1).

Dopamine increases renal oxygenation: a clinical study in post-cardiac surgery patients.

Background: Imbalance of the renal medullary oxygen supply/demand relationship can cause ischaemic acute renal failure (ARF). The use of dopamine for prevention/treatment of ischaemic ARF has been questioned. It has been suggested that dopamine may increase renal oxygen consumption (RVO2) due to increased solute delivery to tubular cells, which may jeopardise renal oxygenation. Information on the effects of dopamine on renal perfusion, filtration and oxygenation in man is, however, lacking. We evaluated the effects of dopamine on renal blood flow (RBF), glomerular filtration rate (GFR), RVO2 and renal O2 demand/supply relationship, i.e. renal oxygen extraction (RO2Ex).

Effects of Cardiopulmonary Bypass on Renal Perfusion, Filtration, and Oxygenation in Patients Undergoing Cardiac Surgery

Background: Acute kidney injury is a common complication after cardiac surgery with cardiopulmonary bypass. The authors evaluated the effects of normothermic cardiopulmonary bypass on renal blood flow, glomerular filtration rate, renal oxygen consumption, and renal oxygen supply/demand relationship, i.e., renal oxygenation (primary outcome) in patients undergoing cardiac surgery. Methods: Eighteen patients with a normal preoperative serum creatinine undergoing cardiac surgery procedures with normothermic cardiopulmonary bypass (2.5 l · min−1 · m−2) were included after informed consent. Systemic and renal hemodynamic variables were measured by pulmonary artery and renal vein catheters before, during, and after cardiopulmonary bypass. Arterial and renal vein blood samples were taken for measurements of renal oxygen delivery and consumption. Renal oxygenation was estimated from the renal oxygen extraction. Urinary N-acetyl-&bgr;-D-glucosaminidase was measured before, during, and after cardiopulmonary bypass. Results: Cardiopulmonary bypass induced a renal vasoconstriction and redistribution of blood flow away from the kidneys, which in combination with hemodilution decreased renal oxygen delivery by 20%, while glomerular filtration rate and renal oxygen consumption were unchanged. Thus, renal oxygen extraction increased by 39 to 45%, indicating a renal oxygen supply/demand mismatch during cardiopulmonary bypass. After weaning from cardiopulmonary bypass, renal oxygenation was further impaired due to hemodilution and an increase in renal oxygen consumption, accompanied by a seven-fold increase in the urinary N-acetyl-&bgr;-D-glucosaminidase/creatinine ratio. Conclusions: Cardiopulmonary bypass impairs renal oxygenation due to renal vasoconstriction and hemodilution during and after cardiopulmonary bypass, accompanied by increased release of a tubular injury marker.

Effects of acute plasma volume expansion on renal perfusion, filtration, and oxygenation after cardiac surgery: a randomized study on crystalloid vs colloid

BACKGROUND In the present randomized study, we evaluated the differential effects of a colloid and a crystalloid fluid on renal oxygen delivery (RD(O2)), glomerular filtration (GFR), renal oxygen consumption ((RV(O2))), and the renal oxygen supply-demand relationship (i.e., renal oxygenation) after cardiac surgery with cardiopulmonary bypass. METHODS Thirty patients with normal preoperative renal function, undergoing uncomplicated cardiac surgery, were studied in the intensive care unit in the early postoperative period. Patients were randomized to receive a bolus dose of either a crystalloid (Ringers-acetate 20 ml kg(-1), n=15) or a colloid solution (Venofundin) 10 ml kg(-1), n=15). Systemic haemodynamics were measured via a pulmonary artery catheter. Renal blood flow and GFR were measured by the renal vein retrograde thermodilution technique and by renal extraction of 51Cr-EDTA (=filtration fraction). Arterial and renal vein blood samples were obtained for measurements of renal oxygen delivery (RD(O2)) and RV(O2). Renal oxygenation was estimated from the renal oxygen extraction. RESULTS Despite an increase in cardiac index and renal blood flow with both fluids, neither of the fluids improved RD(O2), because they both induced haemodilution. The GFR increased in the crystalloid (28%) but not in the colloid group. The crystalloid increased the filtration fraction (24%) and renal oxygen extraction (23%), indicating that the increase in GFR, the major determinant of RV(O2), was not matched by a proportional increase in RD(O2). CONCLUSIONS Neither the colloid nor the crystalloid improved RD(O2) when used for postoperative plasma volume expansion. The crystalloid-induced increase in GFR was associated with impaired renal oxygenation, which was not seen with the colloid. CLINICAL TRIAL REGISTRATION NCT01729364.

Renal tubular injury during cardiopulmonary bypass as assessed by urinary release of N‐acetyl‐ß‐D‐glucosaminidase

Acute kidney injury (AKI) is a common complication with a major impact on morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB). The aim of the present study was to perform a detailed analysis on the release of the tubular injury biomarker N‐acetyl‐b‐D‐glucosaminidase (NAG) during and early after CPB and to describe independent predictors of maximal tubular injury. We hypothesized that renal tubular injury occurs early after the onset of CPB.