Cardiac surgery and the kidney - studies on the effects of pharmacological interventions on renal perfusion, filtration and oxygenation

University dissertation from University of Gothenburg

Abstract: Acute kidney injury (AKI) commonly complicates cardiac surgery and is associated with high mortality. Renal ischemia is considered to be the major cause. There is a close association between glomerular filtration rate (GFR), tubular sodium reabsorption and renal oxygen consumption (RVO2) in humans. The filtered load of sodium is an important determinant of RVO2 and any agent that increases GFR has the potential to increase RVO2. An ideal agent to treat patients with AKI would be one that increases both renal blood flow (RBF) and GFR, with no impairment in renal oxygenation, defined as the renal oxygen supply/demand relationship, the inverse of this relationship being the renal extraction of O2 (RO2Ex). Data on the effects of pharmacological interventions on RBF, GFR and renal oxygenation, are scarce. Patients and methods: The renal vein thermodilution technique was used to analyse the effects of vasopressin (n=12) and the effects of levosimendan vs placebo (n=30), on RBF, GFR and renal oxygenation in post-cardiac surgery patients. The effects of mannitol on RBF, GFR and renal oxygenation were studied in patients (n=11) with AKI after cardiac surgery. The agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, in comparison to GFR, measured by the infusion clearance of 51Cr-EDTA, were evaluated in critically ill patients with AKI. Results: Vasopressin increased renal vascular resistance (RVR) and decreased RBF, while GFR, RVO2 and RO2Ex increased. Mannitol in AKI, increased urine flow, decreased RVR and increased RBF. Mannitol tended to increase GFR and RVO2 but did not change RO2Ex. Compared to placebo, levosimendan decreased RVR and increased RBF and GFR, while RVO2 and RO2Ex were not affected. Finally, the within-group error was higher for the urinary CrCl method than the 51Cr-EDTA clearance method. The urinary CrCl method and the estimating equations had high biases and high errors compared to GFR measured by 51Cr-EDTA. Conclusion: The vasopressin-induced increase in GFR was caused by post-glomerular renal vasoconstriction, accompanied by an increase in RVO2 and RO2Ex. Thus, vasopressin impaired renal oxygenation. Mannitol treatment of AKI induced a renal vasodilation and increased RBF. Mannitol did neither affect filtration fraction nor renal oxygenation, suggestive of balanced increases in perfusion/filtration and oxygen demand/supply. Levosimendan induced a vasodilation, preferentially of pre-glomerular resistance vessels, increasing both RBF and GFR without jeopardizing renal oxygenation. Levosimendan could therefore be a potentially useful agent for treatment of AKI in patients with heart failure. Assessment of GFR by the urinary CrCl method, had a poor precision in critically ill patients with AKI, and should not be used as a reference method, when validating new methods for assessing kidney function in this patient population. All the estimating equations performed poorly, when estimating GFR in these patients.

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