Intraoperative and Postoperative Hemodynamic Predictors of Acute Kidney Injury in Pediatric Heart Transplant Recipients

Abstract

Acute kidney injury (AKI) is common after pediatric heart transplantation (HT) and is associated with inferior patient outcomes. Hemodynamic risk factors for pediatric heart transplant recipients who experience AKI are not well described. We performed a retrospective review of 99 pediatric heart transplant patients at Lucile Packard Children's Hospital Stanford from January 1, 2015, to December 31, 2019, in which clinical and demographic characteristics, intraoperative perfusion data, and hemodynamic measurements in the first 48 postoperative hours were analyzed as risk factors for severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage ≥ 2). Univariate analysis was conducted using Fisher's exact test, Chi-square test, and the Wilcoxon rank-sum test, as appropriate. Multivariable analysis was conducted using logistic regression. Thirty-five patients (35%) experienced severe AKI which was associated with lower intraoperative cardiac index ( p  = 0.001), higher hematocrit ( p  < 0.001), lower body temperature ( p  < 0.001), lower renal near-infrared spectroscopy ( p  = 0.001), lower postoperative mean arterial blood pressure (MAP: p  = 0.001), and higher central venous pressure (CVP; p  < 0.001). In multivariable analysis, postoperative CVP >12 mm Hg (odds ratio [OR] = 4.27; 95% confidence interval [CI]: 1.48–12.3, p  = 0.007) and MAP <65 mm Hg (OR = 4.9; 95% CI: 1.07–22.5, p  = 0.04) were associated with early severe AKI. Children with severe AKI experienced longer ventilator, intensive care, and posttransplant hospital days and inferior survival ( p  = 0.01). Lower MAP and higher CVP are associated with severe AKI in pediatric HT recipients. Patients, who experienced AKI, experienced increased intensive care unit (ICU) morbidity and inferior survival. These data may guide the development of perioperative renal protective management strategies to reduce AKI incidence and improve patient outcomes.

Introduction

Acute kidney injury (AKI) is common after heart transplantation (HT), occurring in 63 to 73% of pediatric HT recipients. ^{1 2 3 4} AKI has been associated with several important postoperative complications, including prolonged mechanical ventilation and inotrope need, hospital length of stay (LOS), and in-hospital mortality, as well as inferior long-term kidney outcomes. ^{5 6 7}

Although several studies have attempted to identify risk factors for AKI in this population, clinical predictors for postoperative AKI in HT patients are not well understood. ^{1 2 3 8} In 2016, MacDonald et al reported a 73% incidence of AKI in pediatric HT recipients, with pre-HT mechanical ventilation and higher baseline estimated creatinine clearance reported as independent risk factors ² ; however, this study did not examine the relationship between intraoperative or postoperative hemodynamics and kidney injury. Similarly, Menon et al, Williams et al, and Hollander et al reported AKI rates of 63, 65, and 72% in pediatric HT recipients, respectively, but clinical predictors for AKI were not identified in any of these studies. ^{1 8 9}

One problem is that studies of children, adolescents, and adults have focused primarily on presurgical risk factors such as low cardiac output, prior exposure to cardiopulmonary bypass (CPB), and history of ventricular assist device (VAD) use rather than intraoperative and postoperative hemodynamics which have been associated with AKI in children undergoing surgery for congenital heart disease (CHD). ^{10 11 12 13 14 15} Despite some similarities to these patients, children and adolescents undergoing HT are a subpopulation of pediatric cardiac surgical patients with unique risk factors who are likely at increased risk for AKI above their CHD surgery counterparts. ^{3 11 12 13 14 15} Postoperative systolic and diastolic dysfunction resulting in low cardiac output and/or systemic venous congestion coupled with exposure to nephrotoxic medications in patients with preexisting renal dysfunction from long-standing heart failure all may predispose HT patients to AKI. ^{9 16 17 18 19 20} Identification of hemodynamic predictors of AKI in pediatric HT patients may guide clinical practice aimed at reducing this frequent complication which has been associated with chronic kidney disease and inferior patient outcomes. ^{1 2 3 8}

The purpose of this study was to identify perioperative and postoperative hemodynamic risk factors for AKI in HT recipients and to describe the relationship between AKI and intensive care unit (ICU) morbidity, as well as mortality in this population. We hypothesized that lower intraoperative cardiac index, lower postoperative mean arterial pressure (MAP), and higher postoperative central venous pressure (CVP) would predict early AKI. We also hypothesized that early AKI would be associated with intensive care morbidity, including longer duration of intubation and ICU LOS.

Materials and Methods

Study Population and Patient Selection

We retrospectively reviewed a contemporary cohort of all patients who received orthotopic HT at Lucile Packard Children's Hospital, Stanford between January 1, 2015, and December 31, 2019. Patients were excluded from the analysis if they underwent multiorgan transplant, required extracorporeal membrane oxygenation, or died within 7 days of HT, or for whom perfusion data were not available. Data were collected until August 1, 2021.

Predictor Variables

Baseline demographics, including age, sex, and race, were obtained retrospectively from the medical record. Clinical data, including pretransplant cardiac diagnosis, pretransplant systemic ventricular function, history of pretransplant mechanical circulatory support, listing status at HT, and total days spent on the waitlist and donor graft ischemic time were also recorded. Operative variables collected while on CPB included cardiac index and MAP which were recorded by the perfusionist at 5-minute intervals during the bypass period. Additional intraoperative independent variables collected during the CPB period included hematocrit (HCT; goal, 30–40%), renal near-infrared spectroscopy (NIRS) saturation, lowest body temperature, and intravenous (IV) phenylephrine administration to maintain blood pressure. The number of values collected varied by patient but typically ranged between 35 and 60 for all values except for NIRS which typically had fewer recorded values and were not available for every patient. Postoperatively, the variables, systolic blood pressure (SBP), diastolic blood pressure (DBP), MAP, and CVP, were collected via indwelling pressure catheters from the time of ICU admission through 48 hours postoperatively, starting at a minimum of every 15 minutes and spacing out to no less than hourly as patients stabilized. From these, mean perfusion pressure (MPP; defined as mean MAP – mean CVP) and mean diastolic perfusion pressure (DPP; defined as mean DBP – mean CVP) were calculated. The mean of each of these values over the data collection period was then calculated by dividing the sum of all values for each data point by the number of values recorded (i.e., “mean MAP” = the mean of all MAP values for that patient).

Outcome Variables

The primary outcome variable was the development of AKI in the first 7 postoperative days. As with other studies in nonrenal pediatric solid organ transplantation and critically ill children, AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria. ^{1 5 6 8 21 22 23} The urine output criteria was not used. Severe AKI was defined as AKI stage 2 or greater (≥2 times of baseline). Baseline preoperative serum creatinine was defined as the preoperative value recorded closest to the time of HT, usually drawn within 24 hours prior to surgery. Estimated glomerular filtration rate was calculated using the Schwartz formula. ^{24 25} Clinical outcome variables included post-HT intubation days, post-HT ICU LOS, post-HT hospitalization LOS, and death from any cause at any point post-HT through the end of the data collection period.

Perfusion Strategy

All transplants were performed on CPB using standard cannulation techniques; no cases required deep hypothermic circulatory arrest. Patients were cooled to a target temperature of 28°C and perfusion flow rates maintained at 100 mL/kg or a cardiac index of 1.8 L/min/m ² with a goal MAP of at least 60 mm Hg while at reduced temperature. Higher flow rates were targeted during rewarming, with perfusion flow rates up to 200 mL/kg or a cardiac index greater than 2.4 L/min/m ² . IV phenylephrine titrated at 5-µg increments was given at the discretion of the perfusionist to maintain target blood pressures while on CPB.

Immunosuppression

All patients received induction therapy consisting of methylprednisone (15 mg/kg IV) intraoperatively followed by rabbit-antithymocyte globulin (1.5 mg/kg/IV daily × 5 days). Plasmapheresis (1.5 volume exchange) followed by IV immunoglobulin (2 g/kg) was given per protocol intraoperatively in the setting of alloantibody presensitization. Postoperatively, all patients received maintenance immunosuppressive therapy consisting of mycophenolate mofetil and solumedrol starting on postoperative day 0 and a calcineurin inhibitor (tacrolimus in 84 [85%], cyclosporine in 15 [15%]) initiated after AKI resolved between 3 and 7 days after HT. Initial tacrolimus and cyclosporine dosing were modulated to achieve target troughs of 10 to 12 or 300 to 350 ng/mL, respectively. Most patients were initiated on loop diuretics within 24 to 72 hours of surgery at the discretion of the attending ICU physician.

Statistical Analysis

Characteristics for the whole cohort, as well as for the groups of patients who did and did not develop AKI were tabulated using count (%) or median (interquartile range [IQR]). Univariate analysis was conducted using Fisher's exact test for binary variables, Chi-square test for categorical variables, and the Wilcoxon rank-sum test for continuous variables with statistical significance assessed at the p  < 0.05 level.

Multivariable analysis for the primary outcome (severe AKI) was conducted using logistic regression taking into account potential confounders in the relationship between perioperative and postoperative hemodynamic risk factors and AKI. To simplify the model and use the most clinically intuitive values, we used a predetermined set of intra- and postoperative characteristics believed to be clinically relevant. For further simplification, we used postoperative mean CVP and mean MAP rather than the calculated values MPP and DPP or DBP (a component of MAP). Similarly, because donor age, recipient age, and body surface area were highly collinear (Pearson's correlation coefficient = 0.8–0.92, p  < 0.001), only recipient age was included in the model. Furthermore, because the scale and clinical significance of 1-unit changes in cardiac index, MAP, CVP, and HCT varied widely, these measures were coded as binary variables for ease of interpretation of clinical impact. Dichotomization occurred on median value for all variables except for postoperative MAP which was dichotomized at <65 mm Hg (= 25th percentile), an important cut-off identified in other research studies. ²⁶ Lastly, because NIRS data were only available for 46 patients, the impact of lowest renal NIRS was assessed in a subsample of patients with NIRS data.

Multivariable outcomes for secondary outcomes (ventilator days, post-HT ICU days, and post-HT hospital days) were conducted using a Poisson's model for skewed data. Potential risk factors for secondary outcomes included severe AKI, as well as a predetermined set of preoperative characteristics which included recipient age, race, pre-HT diagnosis, pre-HT VAD support, and allograft ischemic time. For all multivariable models, results are reported as odds ratios (OR) or incident rate ratios (IRR) with 95% confidence intervals (CI) as appropriate.

Overall posttransplant survival in patients with and without a history of AKI are depicted with Kaplan–Meier curves. Patients who did not die were censored event free at the end of the data collection period. Comparison of HT survival between those with and without AKI groups was performed using the log-rank test.

Clinical data were collected using RedCap (version: 4.5.2, Vanderbilt University), a web-based application designed to support data capture for research studies. ²⁷ Statistical analysis was conducted using Stata version 16 (College Station, Texas, United States). The protocol for this study was approved by Stanford University's Institutional Review Board Panel on Medical Human Subjects (protocol no.: 9731). Individual consent was waived. The clinical and research activities being reported are consistent with the Principles of the Declaration of Istanbul as outlined in the “Declaration of Istanbul on Organ Trafficking and Transplant Tourism.”

Results

Demographics

A total of 133 transplants were performed during the study period. Of these, 15 (11%) were excluded (13 multiorgan transplants, 1 requiring extra corporeal membrane oxygenation, and 1 who died within 7 days from primary graft dysfunction). Of the remaining 118 patients, 99 (84%) had intraoperative perfusion data available and were included in the final analysis. Baseline characteristics for the study cohort are described in Table 1 .

Table 1. Baseline demographics and clinical characteristics ( n  = 99) .

Variable	All Median (IQR) or number (%) n  = 99	No/mild AKI Median (IQR) or number (%) n  = 64	Severe AKI Median (IQR) or number (%) n  = 35	p -Value (univariate)	OR	95% confidence interval	p -Value (multivariable)
Age (y)	10 (2, 14)	12 (5, 15)	3 (0, 13)	0.005	0.97	0.85–1.11	0.64
Infant (0–0.99 years)	18 (18)	7 (17)	11 (31)	0.01
Child (1–11.99 years)	38 (38)	15 (23)	23 (66)	0.5
Adolescent/young adult (age ≥ 12 years)	43 (43)	34 (53)	9 (26)	0.009
Body surface area at transplant (m 2 )	1.1 (0.6, 1.5)	1.3 (0.7, 1.7)	0.7 (0.4, 1.1)	0.001
Sex (male)	55 (56)	34 (53)	21 (60)	0.5
Race
White	31 (31)	18 (28)	13 (37)	0.7
African American	10 (10)	7 (11)	3 (9)
Latino	42 (42)	27 (42)	15 (43)
Asian/Pacific Islander	14 (14)	10 (16)	4 (11)
Other	2 (2)	2 (3)	0 (0)
Pretransplant diagnosis
Congenital heart disease	50 (51)	27 (42)	23 (66)	0.04	1.01	0.33–3.08	1
Cardiomyopathy	49 (49)	37 (58)	12 (34)
Preoperative ventricular function (≥moderately depressed; n  = 51) a	24 (47)	15 (48)	9 (45)	0.8
VAD	47 (47)	32 (50)	15 (43)	0.5
Total VAD days ( n  = 47)	111 (70, 153)	119 (92, 149)	76 (27, 166)	0.2
Preoperative creatinine clearance (mL/min/1.73 m 2 )	138 (115, 177)	139 (117, 177)	138 (104, 177)	0.7
Total listing days	117 (60, 309)	106 (62, 339)	135 (39, 306)	0.9
Donor age (y)	11 (2, 16)	14 (4, 17)	5 (0, 13)	0.01
Graft ischemic time (min)	227 (184, 254)	216 (177, 258)	231 (209, 245)	0.5
Cardiopulmonary bypass time	206 (166, 254)	200 (160, 251)	206 (178, 254)	0.7
Days to CNI initiation	4 (3, 5)	3 (3, 4)	4 (3, 6)	0.003

Abbreviations: AKI, acute kidney injury; CNI, calcineurin inhibitor; IQR, interquartile range; OR, odds ratio; VAD, ventricular assist device.

^aPatients on systemic ventricular VAD support were not included. One additional patient with intractable arrhythmia and unknown ventricular function at the time of transplant was also excluded.

Sixty-four of 99 (65%) of patients developed AKI in the first 7 postoperative days. Of those, AKI was stage 1 in 29 (45%), stage 2 in 23 (36%), and stage 3 in 12 (19%) patients. Fifty-five percent of patients with AKI had severe disease. Of the 35 patients with severe disease, 20 (57%) developed severe AKI within 24 hours, 8 (23%) within 48 hours, and 4 (11%) within 72 hours. Four (4%) received continuous venovenous hemofiltration in the first postoperative week. Severe AKI developed prior to the administration of calcineurin inhibitors in all patients.

Patients who experienced severe AKI were younger, smaller, were more likely to be transplanted for CHD, and received younger donors than those without AKI ( p  = 0.001–0.01). We found no association between sex, race, pre-HT estimated creatinine clearance, pre-HT VAD use, pre-HT systemic ventricular function, wait list days, or allograft ischemic time and the subsequent development of severe AKI ( p  = 0.2–0.9; Table 1 ).

Intraoperative and Postoperative Predictors of Acute Kidney Injury

Intraoperative and postoperative risk factors for severe AKI are displayed in Table 2 . Intraoperatively, lower mean cardiac index and higher mean HCT were associated with severe AKI as was lower renal NIRS and lower body temperature while on CPB ( p ≤ 0.001).

Table 2. Intraoperative and postoperative risk factors for severe AKI ( n  = 99) .

Variable	All Median (IQR) or number (%) n  = 99	No/mild AKI Median (IQR) or number (%) n  = 64	Severe AKI Median (IQR) or number (%) n  = 35	p- Value (univariate)	OR	95% confidence interval	p- Value (multivariable)
Intraoperative (mean)
Cardiac index	2.9 (1.5, 4.2)	3.8 (2, 4.4)	1.9 (1, 3.3)	0.001	0.62	0.1–3.72	0.6
MAP	57 (52, 63)	57 (53, 62)	57 (51, 63)	0.7	1.86	0.67–5.17	0.2
Hematocrit	35 (32, 38)	34 (32, 37)	37 (35, 39)	<0.001	2.45	0.87–6.88	0.09
Lowest renal NIRS ( n  = 46)	66 (57, 75)	70 (63, 78)	60 (50, 68)	0.001
Phenylephrine given	68 (69)	47 (73)	21 (60)	0.2	0.89	0.3–2.61	0.83
Lowest body temperature (°C)	30 (26, 32)	32 (28, 32)	27 (25, 30)	<0.001
First 48 hours postoperatively (mean)
CVP	12 (10, 14)	11 (9, 13)	13 (12, 15)	<0.001	4.27	1.48–12.3	0.007
SBP	105 (95, 114)	107 (97, 114)	101 (92, 111)	0.1
DBP	58 (51, 62)	60 (55, 64)	52 (49, 59)	<0.001
MAP	73 (67, 77)	75 (70, 78)	68 (64, 75)	0.001	4.9	1.07–22.5	0.04
MPP	61 (55, 67)	64 (58, 68)	56 (51, 61)	<0.001
DPP	47 (41, 52)	50 (44, 54)	42 (36, 47)	<0.001

Abbreviations: AKI, acute kidney injury; CVP, central venous pressure; DBP, diastolic blood pressure; DPP, diastolic perfusion pressure; IQR, interquartile range; MAP, mean arterial pressure; MPP, mean perfusion pressure; NIRS, near-infrared spectroscopy; SBP, systolic blood pressure.

The median values for SBP, DBP, MAP, and CVP in the first 48 postoperative hours for those with and without severe AKI are shown in Fig. 1 . During this period, higher mean CVP and lower MAP were associated with severe AKI ( p ≤ 0.001). Mean SBP was not ( p  = 0.1; Table 2 ).

Fig. 1.

( A – D ): Patients with severe AKI (gray) had higher CVP and lower diastolic blood pressure, and MAP than those without AKI (black) during this period ( p ≤ 0.001). AKI, acute kidney injury; CVP, central venous pressure; MAP, mean arterial pressure.

Multivariable analysis for the primary outcome is displayed in Tables 1 and 2 . Among variables included in the model, postoperative mean CVP >12 mm Hg (OR = 4.27; 95% CI: 1.48–12.3; p  = 0.007) and mean MAP < 65 mm Hg (OR = 4.9; 95% CI: 1.07–22.5; p  = 0.04) retained significance ( Fig. 2A ). In the secondary model of patients with NIRS data, lowest renal NIRS <65% (OR = 8.4; 95% CI: 1.35–52.4, p  = 0.04) and phenylephrine use (OR = 0.05; 95% CI: 0.01–0.47, p  = 0.01) retained significance ( Fig. 2B ).

Fig. 2.

( A ) The odds of developing AKI were 4 times higher in those with a median mean CVP > 12 mm Hg (OR = 4.27; 95% CI: 1.48–12.3; p  = 0.007) and five times higher in those with a mean MAP < 65 mm Hg. ( B ) Among patients with NIRS data available ( n  = 46), the odds of developing severe AKI were eight times higher in patients with renal NIRS ≤65% ( p  = 0.04) and 20 times lower in those receiving phenylephrine while on CPB ( p  = 0.01). AKI, acute kidney injury; CI, confidence interval; CHD, congenital heart disease; CPB, cardiopulmonary bypass; CVP, central venous pressure; MAP, mean arterial pressure; NIRS, near-infrared spectroscopy; OR, odds ratio.

Acute Kidney Injury and Outcomes

In unadjusted analysis, patients who had severe AKI experienced more ventilator days, longer postoperative ICU LOS, and a longer posttransplant hospital LOS ( Table 3 ). Thirteen (13%) of patients died. The median time from transplant to death was 552 (IQR: 238, 1,250) days. Patients with AKI had inferior survival compared with those without AKI ( p  = 0.01; Fig. 3 ).

Table 3. Outcomes associated with severe AKI ( n  = 99) .

Variable	All Median (IQR) or number (%) n  = 99	No/mild AKI Median (IQR) or number (%) n  = 64	Severe AKI Median (IQR) or number (%) ( n  = 35)	p- Value (univariate)	OR/IRR	95% CI	p- Value (multivariable)
Posttransplant hospital days	20 (14, 40)	17 (13, 29)	31 (19, 62)	<0.001	2.39	2.23–2.58	<0.001
Days on ventilator	2 (1, 4)	2 (1, 3)	4 (2, 16)	<0.001	2.99	2.45–3.65	<0.001
Days in ICU	7 (6, 17)	7 (5, 11)	13 (6, 28)	0.005	1.58	1.41–1.76	<0.001

Abbreviations: AKI, acute kidney injury; CI, confidence interval; ICU, intensive care unit; IQR, interquartile range; IRR, incidence rate ratio; OR, odds ratio.

Fig. 3.

Survival was inferior in patients with severe AKI ( p  = 0.01). AKI, acute kidney injury.

Discussion

The present study identifies several clinical and hemodynamic risk factors for AKI in pediatric HT patients. Patients who were younger and smaller, as well as those transplanted for CHD, were at increased risk. Intraoperative low cardiac index, lower body temperature, higher HCT, and lowest renal NIRS were associated with post-HT AKI as were lower MAP and higher CVP in the first 48 hours postoperatively. Notably, the odds of developing severe AKI were four times greater in patients with a mean CVP >12 mm Hg and nearly five times greater in those with a mean MAP <65 mm Hg in the early postoperative period. In contrast, AKI was not associated with preoperative systemic ventricular function or creatinine clearance and occurred prior to the administration of calcineurin inhibitors.

We also found that patients with severe AKI had increased morbidity, including more ventilator days, more posttransplant ICU days, and longer post-HT hospital stay. Taken together, these findings suggest that intra- and postoperative decreases in renal perfusion resulting from lower cardiac output and/or venous congestion play a more important role in the development of early renal dysfunction than preoperative characteristics which are then associated with inferior patient outcomes.

Our findings that lower cardiac index and MAP, as well as higher CVP predispose pediatric HT patients to AKI, are consistent with similar findings in adults undergoing heart surgery. ^{28 29 30} Decreased arterial pressure coupled with increased CVP results in a decreased transrenal pressure gradient and reduced renal blood flow which may be particularly dangerous for the HT patient beyond the renal risks associated with conventional heart surgery. In HT, ischemic injury to the donor allograft during organ transfer places the patient at risk for diastolic heart failure, venous congestion, and decreased renal perfusion which then leads to reduced urine output and fluid retention. Worsening fluid overload then precipitates further injury to the donor heart from myocardial stretch setting-off a dangerous cycle of more venous congestion, decreased renal blood flow, and worsening renal failure. In addition, chronic hypoxia, prior AKI events, preexisting chronic kidney disease, CPB, and direct renal injury from nephrotoxic immunosuppressive agents all likely contribute to the high rates of AKI seen in children undergoing HT. ^{3 31 32 33 34 35 36}

One interesting finding of this study was the association between lower body temperature while on CPB and AKI. Hypothermia is a recognized risk factor for AKI following cardiac surgery in adults and is likely injurious to the kidneys in two ways. ³⁴ First, hypothermic CPB leads to increased afferent arteriolar pressure, tubular hypoxia, and impaired renal blood flow autoregulation, all of which promote renal medullary ischemia. ^{33 37 38} Second, patient rewarming, particularly in the setting of CPB, aortic cross-clamping, blood product transfusions, and the use of IV inotropic medications for postsurgical recovery, all promote immune activation, oxidative stress, and inflammation, leading to renal reperfusion injury and postoperative AKI. ^{32 34 39 40 41 42 43} Our study is the first to identify a similar association in children undergoing HT and suggests that avoidance of overcooling while on CPB may be a strategy to avoid AKI in this population.

As with other studies in critically ill patients, we found that AKI was associated with increased ICU morbidity, including increased ventilator days and Cardiovascular Intensive Care Unit (CVICU) LOS. ^{2 6 44 45} The present study builds on the literature by also identifying an association with severe AKI and post-HT hospital LOS. Although beyond the scope of this study, it is plausible that AKI predisposes HT patients to ongoing venous congestion and elevated diastolic heart failure that slow myocardial recovery and exacerbate pulmonary edema, necessitating longer postoperative intubation and slower weaning of intensive care therapies.

Our study also found that patients with AKI had inferior survival. This finding is similar to that reported by Menon et al but differs from Williams et al who did not observe increased mortality in patients with a history of AKI ^{1 8} ; however, that study included a broader cohort of solid organ transplant recipients and included AKI events at any point of posttransplant. Our findings of inferior survival in an exclusive cohort of HT patients underscore the important impact of early AKI on patient outcomes in this specific population, even when renal replacement therapy is not required. Given that not all mortalities occurred in the early postoperative period, the mechanism by which early AKI and associated hemodynamic disturbances predisposes patients to increased intermediate-term mortality is unclear.

With the identification of hemodynamic risk factors for AKI in pediatric HT patients, this study offers an opportunity for quality improvement interventions in intra- and postoperative patient management to reduce AKI rates in children undergoing HT. Alternative intraoperative management strategies that favor renal blood flow, increased use of intraoperative renal NIRS with renal arterial oxygen saturation targets, and diligent adherence to “renal protective” MAP and CVP targets in the early postoperative period, all carry the potential to reduce AKI incidence in this population. Given the relationship between AKI and patient outcomes identified in this study, these renal protective maneuvers may also have downstream benefits of reduced ventilator and ICU days and improved patient survival.

Limitations

The present study is limited by its retrospective design and single-center nature, limiting generalizability. Furthermore, we did not include the urine output criteria for AKI and relied on estimated glomerular filtration rate (GFR) rather than measured creatinine clearance which may have resulted in underestimated AKI incidence. This study also did not analyze hemodynamics before or after CPB in the operating room or the effect of intraoperative hypotensive events, nor did it analyze the impact of postoperative inotrope use on AKI. Nevertheless, the present study demonstrates the relationship between intraoperative and postoperative hemodynamics and AKI development, as well as the impact of early AKI on patient outcomes. This study also underscores the potential benefit of “renal protective” hemodynamic management strategies in this at-risk population, an important area for future study.

Conclusion

The present study demonstrates the relationship between intraoperative and postoperative hemodynamics and AKI development, as well as the impact of early AKI on patient outcomes. Patients, who experienced AKI, experienced increased ICU morbidity and inferior survival. These data may guide perioperative renal protective management strategies to reduce AKI incidence and improve patient outcomes.