Maria Tholén- Acute kidney injury after cardiac surgery and heart transplantation - monitoring, prevention and treatment

Link directly to the doctoral thesis

ABSTRACT

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Background: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery and heart transplantation, leading to increased morbidity and mortality. To date, there are neither proven clinical real-time kidney monitoring techniques, nor effective preventive measures or treatments of AKI for these patients.

Aims and methods: This thesis evaluated whether the non-invasive technique, near-infrared spectroscopy (NIRS), can accurately assess renal tissue oxygenation in patients during cardiac surgery. Renal vein oxygen saturation (SrvO2) was compared to renal tissue oxygenation (rSO2) by NIRS. Furthermore, the effects of the inodilator, levosimendan (0.1 µg/kg/min, n=16), on renal blood flow (RBF) and glomerular filtration rate (GFR) were compared to placebo (n=13) in patients with AKI post cardiac surgery. In addition, the renoprotective effect of the atrial natriuretic peptide (ANP) was studied in patients undergoing heart transplantation. Seventy patients undergoing heart transplantation were randomized to receive either ANP (50 ng/kg/min) (n=33) or placebo (n=37) starting after induction of anaesthesia and continued for 4 days after heart transplantation. The primary end-point was measured GFR (mGFR) at day 4, assessed by plasma clearance of 51Cr-EDTA. Finally, the correlation, accuracy and agreement between estimated GFR (eGFR) and measured GFR (mGFR) were tested after heart transplantation.

Results: Renal rSO2, as assessed by NIRS, was correlated to (r=0.61. p<0.001), and in agreement with invasively measured SrvO2 with an acceptable error of 17.6%. In hemodynamically stable patients with AKI after cardiac surgery, levosimendan increased RBF (p=0.011), but had little or no effect on GFR (p=0.079). During ongoing ANP infusion, median (IQR) mGFR at day 4 postoperatively was 60.0 (57.0) and 50.1 (36.3) mL/min/1.73 m2 (p=0.705) and the need for dialysis was 21.6% and 9.1% (p=0.197) for the placebo and ANP groups, respectively. The incidences of AKI for the placebo and the ANP groups were 76.5% and 63.6%, respectively (p=0.616). The accuracy of eGFR to assess mGFR was 51%. The bias was 11.2 ± 17.4 mL/min/1.73 m2, indicating that eGFR underestimated renal function (mGFR). The limits of agreement were -23.0 to 45.4 mL/min/1.73 m2 and the error 58%. The concordance rate between eGFR and mGFR was 72%

Conclusions: There is a good correlation and agreement between non-invasively measured renal tissue oxygenation and invasively measured renal vein oxygen saturation during cardiac surgery. In post cardiac surgery AKI, levosimendan induces a vasodilation of both afferent and efferent arterioles increasing renal blood flow with little or no effect on renal function. Prophylactic infusion of ANP during and after heart transplantation does not seem to attenuate postoperative renal dysfunction or decrease the incidence of AKI. eGFR underestimated mGFR and the agreement between eGFR and mGFR was poor. Furthermore, the ability of eGFR to assess changes in mGFR, postoperatively, was low. Thus, eGFR is not a good enough marker to assess renal function after heart transplantation.