The principal findings of this single-centre, retrospective PSM study can be summarized as follows. (1) AKI of any severity occurred in 40.3% of all CABG patients aged older than 70 years, with AKIN stage 1 accounting for most AKI cases(71.8%). New onset of dialysis was applied in 2.3% of all patients. (2) Comparing with on-pump CABG, off-pump CABG was neither associated with decreased rate or severity of postoperative AKI nor with decreased long-term new onset of dialysis or mortality in such cohort. (3) Postoperative in-hospital AKI increased the rate of new onset of dialysis and decreased the survival rate in long-term follow-up.
PSM analysis provided the opportunity to rule out confusion by providing balanced baseline and procedural characteristics except the application of CPB. Certainly there was no significant difference in other factors, including the experience of surgeons. The univariate factor analysis manifested that the two PSM groups had similar in-hospital mortality and most of morbidities.
AKI occurs in up to 30% of patients undergoing CABG, depending on the underlying definition[13]. The rate of new onset of renal dialysis following cardiac surgery ranged from 1-6%[14]. Veterans Affairs Randomized On/Off Bypass (ROOBY) trial showed new renal dialysis within 30 days postoperatively was 0.9%[15]. Garg et al. performed a detailed analysis evaluating kidney function of the CORONARY patient population, overall 1.2% of these patients needed new renal dialysis[16,17]. In our study, AKI was a common complication that occurred in 40% of all patients, and 2.3% needed renal dialysis. The incidence in our study was higher than that reported in the literatures. In addition, the incidence of new renal dialysis for AKI patients was 4.5% in our study, which was obviously higher than the average. The same result was obtained by Wilko Reents et al., they promoted a study named” The German Off Pump Coronary Artery Bypass Grafting in Elderly Patients (GOPCABE)”, which only enrolled patients aged 75 years or older to CABG with or without CPB[18]. It is therefore reasonable to assume that the relative high rate of AKI and new renal dialysis in our study was mainly due to the high proportion of particularly vulnerable elderly patients with preexisting kidney dysfunction, as was shown in table1, average baseline GFR was only about 81ml/min/1.73m2. As is reported that age and preoperative renal dysfunction are both independent risk factors of AKI[19].
CPB still contributes to renal injury due to multiple perturbations in renal physiology and function as mentioned before. Off-pump technique seems to be a logical step toward preventing postoperative AKI. However, the effect of off-pump CABG on kidney function is still discussed controversially in literatures[20,21]. The largest single randomized trial (CORONARY) found an absolute 4.1% risk reduction of AKI for off-pump CABG, but the reduction was contributed only by decreased occurrence of AKI stage 1, more severe stages of AKI or new renal dialysis were of no significant differences between the two groups, our center was also one of the collaborators of the CORONARY study[16]. A meta-analysis of 37 randomized controlled trials (n =3,449) and 22 risk-adjusted observational studies (n =293,617) concluded that the benefit for off-pump CABG was only in the observational studies, but the difference was not significant in the aggregate randomized trials[22].
In this study we also found that compared with on-pump CABG, off-pump CABG was not associated with decreased rate or severity of AKI in elderly patients. We speculated the reasons were as follows: (1) The different definitions of AKI used in this study and methodological concerns precluded definitive conclusions from other trials. (2) Average CPB duration(mean time was 78.4 min) was relatively short, which attenuated pump-induced hemolysis, thereby releasing hemoglobin and free iron, and injuring the renal tubule[23]. (3) Relative high perfusion pressure was kept to guarantee the renal perfusion, especially in elderly patients undergoing on-pump surgery[24]. (4) The inflammatory response did not differ greatly between on-pump and off-pump groups[25,26]. (5) When performing the anastomosis of the lateral vessels, transient circulatory failure and global hypoperfusion (renal malperfusion) often occurred during the off-pump surgery. (6) Atheroembolism caused by aortic manipulation(cross and side clamping) is another possible reason of renal impairment, which may occur in both on- and off-pump surgery. (7) On-pump technique provided improved complete revascularization, so it is conducive to the recovery of cardiac function and renal perfusion. (8) There are no active treatments for AKI, and therefore, perioperative preventative strategies seem particularly promising. Keep adequate hydration and avoid the use of diuretics; minimize the use of medications with adverse effects on renal function; keep an optimal hemodynamic status and correct the acid-base or metabolic imbalance. All of the aboved strategies might offset the differences in renal impairment between the two groups.
As expected, the follow-up demonstrated that in-hospital AKI patients showed a trend to higher new onset of dialysis (2.4% vs 0.2%, p=0.004) and lower long-term survival (89.5% vs 94.2%, p=0.012) compared with non-AKI patients in this study. Cox regression manifested that postoperative in-hospital AKI was a significant variable related to the new onset of dialysis and long-term mortality, and the HR was 1.83 and 1.31 respectively (95%CI 1.12-2.86, p=0.007; 95%CI 1.17-2.58, p = 0.015). This study was consistent with our previous study and some other studies which demonstrated that development of AKI was associated with high short-term and long-term morbidity and mortality[18,27]. AKI has been associated with progression to chronic kidney disease(CKD) and dialysis in many reports[28]. CKD and dialysis might exert negative efferts on the long-term survival inevitably especially in elderly patients[29]. Unfortunately, there are no pharmacologic agents known to reduce the risk of AKI or treat established AKI. Therefore, AKI patients after CABG need to strengthen the follow-up of nephropathy, more strictly management of the risk factors of coronary artery disease postoperatively.
Limitations
Firstly, a retrospective, non-randomized single-centre analysis over a long period of time and with different surgeon’s procedures on patients undergoing CABG is subjected to the effects of selection bias,for example, low percentage of female patients and high percentage of patients with good ventricular function, baseline GFR was>80%. Although PSM is implemented, a prospective, multi-centre study involving larger sample size is needed. Secondly, the GFR was derived by using the MDRD formula, which was not designed for determining GFR. Thirdly, the initial RIFLE criteria do not include the creatinine increase within 48 hours for defining the mildest form of AKI, whereas the RIFLE categories injury and loss are similar to AKIN stage 2 and 3, respectively. AKI defined according to the RIFLE criteria may therefore avoid an iatrogenic hemodilution but may miss more subtle changes of kidney function[18]. Finally, on-pump CABG is usually associated with more grafts and more transfusions, but after PSM with off-pump group, some on-pump cases have to be excluded.