Results of this pilot trial showed that, for patients undergoing partial nephrectomy for renal cancer, goal-directed fluid and blood pressure management reduced AKI by about 40%. However, the trial was under-powered. Large randomized controlled trials are required to confirm our results.
In the present study, AKI occurred in 20.8% of control group patients. This was lower than we expected [5], but was still within the reported range [5–8, 24, 25]. Two reasons might explain the unexpected lower incidence of AKI in our control group patients. The first one is the diagnostic criteria. AKI is usually diagnosed within 7 postoperative days according to the KDIGO criteria. In the study center, most patients were discharged within 3 to 4 days after partial nephrectomy, diuretics were often used during surgery and it was difficult to monitor urine output per hour in the ward. Therefore, we diagnosed AKI only according to serum creatinine change within 3 postoperative days. This might have underestimated the rate of AKI development. However, recent studies showed that the majority of surgery-related acute kidney injury occurred within 48 hours of surgery [26]. Secondly, the improvement of surgeons’ skill and surgical technique helped preserve renal function. For example, the durations of renal hilus clamping and surgery were shorter in our patients than in previous studies [8, 24, 25].
Routine circulatory management during partial nephrectomy is to maintain blood pressure change within 20% from baseline and urine output > 0.5 ml/kg/h. However, the incidence of AKI remains high after surgery [8, 24, 25]. Experience from kidney transplantation suggested that maintaining adequate renal hydration and higher blood pressure after reperfusion (i.e., CVP > 8 mmHg and MAP > 95 mmHg) are beneficial for graft function [14, 15, 18]. Similar hemodynamic therapy may also relieve ischemia-reperfusion injury and protect renal function after partial nephrectomy.
Kidney is more sensitive to inadequate hydration compared with other organs. As Myles et al. [27] reported, restrictive fluid therapy is associated with a higher risk of AKI in renal transplant recipients. Static cardiac filling pressures such as CVP correlate poorly with the intravascular volume [28]; and hydration according to static parameters may induce excessive fluid infusion [29]. Better hemodynamic monitoring can be achieved with LiDCOrapid, a minimal invasive device that can monitor SVV, cardiac output and cardiac index through pressure contour analysis [30]. As a dynamic parameter, SVV is capable to reflect volume responsiveness and replace CVP [19, 28]. It was found that the optimal cutoff value of SVV is 6% and can be used as an alternative to CVP of 8 mmHg during kidney transplantation [19]. Therefore, SVV was maintained < 6% in this pilot trial as a hydration goal.
Cardiac output is an indicator of oxygen delivery and organ perfusion but is often compromised during general anesthesia. Studies showed that low-dose inotropic therapy is associated with an improved global oxygen delivery and tissue oxygenation [11]. However, in the study of Pearse et al. [12], cardiac-output guided hemodynamic management did not reduce complications including AKI after major gastrointestinal surgery. To be noted, dopexamine, a β2-agonist with both inotropic and vasodilator effects, was infused to obtain cardiac inotropy in the above study; blood pressure was ignored and might even be lower than usual due to the vasodilator effects of dopexamine, and as a result renal perfusion pressure was not guaranteed. In clinical practice, dopamine is also frequently used to increase blood pressure during kidney transplantation. But studies indicate that dopamine does not improve kidney function; on the contrary, it may produce potential harmful effects [31]. In this pilot study, dobutamine was adopted to maintain normal cardiac output and MAP > 95 mmHg in the intervention group; norepinephrine was infused if necessary.
This pilot study was the first to explore the effect of goal-directed circulatory management on renal function after partial nephrectomy. It seems that circulatory management with the goals of SVV < 6%, MAP > 95 mmHg and CI 3.0–4.0 L/min/m2 based on LiDCOrapid hemodynamic monitoring didn’t significantly reduce postoperative AKI when compared with routine circulatory management, very possibly due to under-powered sample size. However, the relative risk reduction of AKI approaches 40%, which cannot be ignored and is clinically important. Our trial was underpowered because AKI incidence was lower than expected, and intervention reduced AKI by 40% rather than anticipated 52%. With the baseline AKI incidence of 20.8% and treatment effect of 40%, 626 patients would be required to provide 80% power. Further studies with larger sample sizes are needed to confirm our results.
Our study confirmed that patients’ overall renal function declined after surgery and, of those who developed AKI, most had mild renal injury. Our results were similar to previous studies [8]. Severe AKI is associated with increased mortality [32]; furthermore, mild AKI also negatively affected long-term functional recovery after partial nephrectomy and may increase the proportion of CKD upstaging [33, 34].
There are some limitations in this trial. First, as a single-center study, the generalizability of our results may be limited. Second, interventions could not be blinded to anesthesiologists taking care of patients, which may bring bias. To reduce the related bias, anesthesiologists did not participate in patient recruitment and postoperative follow-up; whereas investigators who performed follow-ups were masked from study group assignment. Third, as a pilot study, the limited sample size diminished study power.