In our retrospective analysis, we found that AKI was a frequent complication of HTx, with an incidence of 36.1%. We also showed that a relatively short CPB time and increased intraoperative urine volume could prevent the occurrence of AKI. Furthermore, AKI requiring RRT was an independent risk factor for mortality after HTx. Finally, AKI requiring RRT was associated with an increased risk for short-term mortality but not long-term mortality.
Severe AKI is an important independent contributor to mortality in the HTx population. Accumulating evidence indicates that AKI requiring RRT could be a strong predictor of adverse clinical outcomes. In Renata’s study, patients with AKI, especially those requiring RRT (46.9%), had higher hospital mortality (16%) than those without AKI [14]. However, after hospital discharge, AKI was not associated with poor long-term outcomes. With a median follow-up after hospital discharge of 6.7 years, overall survival at 1, 5, and 10 years was 95.4%, 85.1%, and 75.4% and 85.2%, 69.8% and 63.5% among patients with AKI stages 2 and 3, respectively [14]. Fortrie’s findings showed that one-year mortality rates in patients without AKI and with AKI stages 1, 2, and 3 were 4.8%, 7.6%, 11.8%, and 14.7%, respectively.7 In an extensive follow-up of 471 HTx patients over a period up to 26 years, no association was found between the development of AKI and long-term mortality or chronic RRT dependence [15]. In this study, we found that one-year mortality in patients with AKI was 26.92%, and the incidence rate of AKI requiring RRT was 50%. Moreover, overall survival in patients without AKI at 1, 3, and 5 years was higher than that in AKI patients.
In contrast to the high overall incidence of AKI, the need for RRT in our study was 18.05%. This is similar to previous studies reporting a need for RRT in 6–29% of patients [2, 4, 6]. A recent analysis indicated that AKI requiring RRT had a 1-year mortality rate of 59.2% [16]. In Boyle’s study, AKI requiring RRT was associated with a mortality rate of 50% compared to 1.4% in patients without AKI [17]. We estimated an increased risk for mortality, with a hazard ratio of 6.402 in AKI patients requiring RRT. These results could be explained by the fact that patients with severe AKI are less likely to achieve full recovery of kidney function, even with RRT, than patients with mild AKI. In fact, some AKI patients requiring RRT develop at least one other serious complication (sepsis, graft failure, or acute myocardial infarction), which can lead to early mortality during the postoperative care period. In our study, there was a nonsignificant tendency toward an increase in long-term mortality in AKI patients requiring RRT, which is consistent with previous reports.3 Therefore, the impact of RRT appears to be lost at long-term follow-up. This result indicated that recovery of kidney function prior to hospital discharge was associated with decreased long-term mortality risk.
The interactions between the heart and kidney systems have become a matter of great concern [18]. The difference between arterial driving pressure and venous outflow pressure must remain sufficiently large for adequate renal blood flow and glomerular filtration. The low-resistance nature of the renal vasculature and parenchyma and the very low oxygen tension in the outer medulla also explain the unique sensitivity of the kidneys to hypotension-induced injury [2, 19]. Thus, both hemodynamic instability and antecedent hypotension should be considered in the consultative evaluation of a patient with developing AKI.
Several factors have been suggested to contribute to the development of postoperative AKI. In general, the most common cause in the early postoperative period is ischemic-reperfusion injury [20]. Intraoperatively, maintenance of a mean arterial pressure (MAP) > 60–65 mmHg, reduction in CPB time, minimization of blood transfusion and avoidance of nephrotoxic agents may prevent AKI [2, 21]. Moreover, increased central venous pressure (CVP) was associated with a reduced GFR and all-cause mortality. Right atrial pressure strongly predicts the development of AKI early after HTx and can be used as an early AKI indicator [22]. Finally, postoperatively, chloride-restricted fluid management was associated with less AKI and RRT [23]. In our opinion, a relatively short CPB time and increased intraoperative urine volume play important roles in preventing the occurrence of AKI after HTx.
The performance and usefulness of different AKI scoring systems with regard to mortality vary greatly [24]. The KDIGO criteria are widely applied in the analysis of AKI in HTx patients. However, the emphasis on SCr and urine volume may exaggerate the severity of AKI. In addition, according to the RIFLE criteria, AKI encompasses the entire spectrum of the syndrome, from minor changes in renal function to the requirement of RRT. Thus, AKI does not simply represent acute renal failure but is a more general description [25]. Since the AKIN criteria are not sensitive enough to capture all episodes of AKI in cardiac surgery patients, they are not widely used for HTx patients [26]. We consider to evaluate this issue in future clinical trials.
A growing body of evidence suggests a disconnect between SCr and adverse outcomes in certain clinical circumstances. SCr can be influenced by volume overload, nutrition, steroids, and muscle trauma; thus, relying solely on SCr for the diagnosis of AKI can be problematic, especially in critically ill patients [27]. In fact, low to moderate SCr levels are anticipated and tolerated and seem unrelated to significant renal injury [28]. Kidney tubular injury biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), plasma cystatin-C (CyC) and kidney injury molecule 1 (KIM-1), can predict the development of AKI [8, 29]. Additionally, NGAL has shown a promising correlation with irreversible renal dysfunction. Thus, these novel biomarkers of early kidney damage represent a new dimension in improving the accuracy of AKI and its treatment targets for the future.
We acknowledge that several limitations exist in this study. The inherent limitation is that it was a retrospective, single-center study that enrolled a small number of patients. Furthermore, the small sample size made it difficult to detect small effects and prevented the use of multivariate analysis. In addition, patients were relatively old and likely to suffer from comorbid conditions, such as diabetes mellitus and hypertension. These comorbidities may interfere with the analysis of the long-term survival rates in AKI requiring RRT. Finally, the indication for dialysis is standardized; however, to some extent, it depends on the physician treating the individual patient, which may have acted as a confounder in our study.