Abstract
Background
The clinical importance of contrast-associated acute kidney injury (CA-AKI), the most common complication after percutaneous coronary intervention (PCI), is debated.
Objectives
We aimed to assess the association between CA-AKI and long-term outcomes, overall and across the National Cardiovascular Data Registry (NCDR) AKI risk categories.
Methods
We analyzed patients undergoing PCI between September 2008 and October 2021 from a Japanese registry aligned with the NCDR and categorized them by the NCDR AKI risk score tertiles (low-risk [<4.9%], intermediate-risk [4.9%-6.7%], and high-risk [≥6.7%]) groups. CA-AKI was defined as a 0.3 mg/dL increase or 50% increase in creatinine or the initiation of dialysis. Cox regression analyses assessed the association between CA-AKI and 2-year major adverse cardiovascular events (MACE; all-cause mortality, acute coronary syndrome, heart failure hospitalization, or stroke), and interactions were tested to examine whether preprocedural risk modified the association of CA-AKI with outcomes.
Results
Of 7,916 patients, 723 (9.1%) developed CA-AKI; its incidence for low-risk, intermediate-risk, and high-risk groups was 2.3%, 7.3%, and 17.9%, respectively. CA-AKI was associated with an increased risk of MACE (adjusted HR [aHR]: 1.64; 95% CI: 1.37-1.97). The interaction between AKI risk profile and MACE was not significant (P interaction = 0.14), and a consistent association of CA-AKI and MACE across risk categories was observed (high-risk, aHR: 1.60; 95% CI: 1.30-1.98; intermediate, aHR: 1.64; 95% CI: 1.10-2.44; and low, aHR: 2.84; 95% CI: 1.43-5.65, respectively).
Conclusions
CA-AKI was associated with long-term outcomes across all AKI risk profiles in PCI patients, underscoring the importance of interventions to reduce periprocedural CA-AKI.
Key words: contrast-associated acute kidney injury, major adverse cardiovascular events, percutaneous coronary intervention, preprocedural risk score
Central Illustration
Contrast-associated acute kidney injury (CA-AKI) is the most frequent periprocedural complication of percutaneous coronary intervention (PCI).1, 2, 3, 4, 5 Importantly, it can be prevented with the use of adequate preprocedural hydration and contrast minimization. To prevent CA-AKI, the National Cardiovascular Data Registry (NCDR) CathPCI registry developed a CA-AKI prediction model with recommendations for safe contrast limits tailored to preprocedural risk.6 This risk model has been independently validated in other countries, underscoring its potential value as a foundation for implementing strategies to minimize CA-AKI through personalized strategies of contrast reduction that can balance patients' risks for CA-AKI with the goals of complete revascularization.7, 8, 9 Further, in a randomized trial, preprocedural use of this model significantly reduced the rate of CA-AKI in high-risk patients.10
CA-AKI as a quality improvement target requires further evidence of its long-term prognostic significance. Although preprocedural risk assessment for PCI has been recommended, the relationship between patient-specific preprocedural CA-AKI risk and long-term outcomes following CA-AKI has not been sufficiently investigated. Limited data describing its enduring clinical impact may diminish motivation to implement preventive strategies.11, 12, 13 One challenge is that CA-AKI is defined by a laboratory threshold (eg, an increase in serum creatinine ≥0.3 mg/dL), which may not inherently resonate with clinicians as clinically meaningful. In addition, most prevention efforts have focused on high-risk patients, leaving relatively little attention to those deemed low-risk, reflecting a gap in understanding CA-AKI's impact across the full spectrum of individuals undergoing PCI.14,15 Although this focus has aided in reducing CA-AKI incidence to some extent, relying on high-risk cohorts alone may overlook broader opportunities for improving outcomes.10 From a quality initiative perspective, understanding the prognostic implication of CA-AKI in a comprehensive spectrum of patients is essential to determine whether prevention strategies should be expanded to include a wider patient population, ultimately enhancing the quality of care.
To address this issue, we leveraged an all-comer registry for patients undergoing PCI to examine the association between the incidence of CA-AKI and long-term adverse clinical outcomes across a broad CA-AKI risk spectrum. Furthermore, we assessed whether the strength of this association differs according to patients' baseline CA-AKI risk.
Methods
Study setting
The Japan Cardiovascular Database-Keio Inter-Hospital Cardiovascular Studies (JCD-KiCS) PCI registry is a prospective, multi-institutional registry that prospectively collects data on consecutive patients undergoing PCI from 15 facilities, primarily large tertiary medical centers.16,17 The JCD-KiCS registry data collection is based on the data elements and definitions of the NCDR CathPCI Registry (version 4.1.2). This registry has been thoroughly developed and validated for AKI prediction models, providing an ideal environment for analyzing this hypothesis.7,8
Participants are followed up to 2 years from the index PCI, and reported cardiovascular events, bleeding events, and all-cause mortality are confirmed through medical records, telephone, and postal mail annually. Each hospital's institutional review board reviewed and approved the study protocol, and all the participants provided written consent. These analyses were also approved by the institutional review board committee of Keio University (reference number: 20080073). We followed the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.
Study population and eligibility criteria
Consecutive patients who underwent PCI from July 2008 to October 2021 who were discharged alive were included (Figure 1). We calculated the NCDR AKI risk score to predict CA-AKI risk for each participant using the NCDR risk model and categorized patients by tertile—low-risk, intermediate-risk, and high-risk.6 This NCDR AKI risk score was developed with recommendations for safe contrast limits tailored to preprocedural risk.6,14 Importantly, the score has also been previously validated in a Japanese dataset.8
Figure 1.
Flow Chart of the Study
Study population and eligibility criteria are shown. AKI = acute kidney injury; JCD-KiCS = Japan Cardiovascular Database-Keio Inter-Hospital Cardiovascular Studies; NCDR = National Cardiovascular Data Registry; PCI = percutaneous coronary intervention.
Those on dialysis before PCI (n = 520), missing pre-PCI creatinine levels (n = 892), and those without postprocedure creatinine levels (n = 383) were excluded, while 1,658 patients were excluded because the NCDR AKI risk score could not be calculated due to missing values. Supplemental Table 1 compares the eligible patients and those excluded due to missing data. The choice of supportive pharmacological treatments, mechanical assistance, contrast use, and the interventional approach were determined at the physicians' discretion.
Definition of AKI and risk stratification of CA-AKI
As defined by the NCDR CathPCI Registry, CA-AKI was defined as a 0.3 mg/dL increase or 50% increase in creatinine or the initiation of dialysis within 30 days of PCI,7 based on the Kidney Disease Improving Global Outcomes consensus criteria. The baseline creatinine was defined as the highest value within 30 days before PCI. Clinical research coordinators collected creatinine levels after PCI from hospital records and outpatient visits within 30 days of PCI. We calculated the estimated glomerular filtration rate (mL/min per 1.73 m2) using the Modification of Diet in Renal Disease Equation for Japanese Patients proposed by the Japanese Society of Nephrology.18
Primary and secondary outcomes
The primary outcome was the 2-year occurrence of major adverse cardiovascular events (MACE), defined as all-cause mortality, acute coronary syndrome (ACS), heart failure hospitalization, or stroke. Secondary outcomes included each individual MACE component. All patients were followed until death or the date of last follow-up. ACS included ST-segment elevation myocardial infarction, non-ST-elevation myocardial infarction, and admissions for unstable angina.
Statistical analysis
Continuous variables are presented as the mean ± SD, and categorical variables are presented as counts and proportions. Baseline patient and treatment characteristics were compared between those with and without CA-AKI. Given the large sample size, baseline characteristics were compared using standardized differences, where an absolute difference of more than 10% was considered important. Cumulative survival probabilities for MACE and all-cause mortality among those with and without CA-AKI were calculated overall and across CA-AKI risk tertiles using Kaplan-Meier curves and groups were compared using the log-rank test. Cumulative incidence curves for ACS, heart failure hospitalization, and stroke were calculated and compared using Gray test, considering death as a competing risk. Cox proportional hazards models were used to estimate the adjusted HRs (aHRs) and 95% CIs of outcomes to define the independent association of CA-AKI and each MACE outcome. Covariates were selected to align with previous studies15,19 as the primary model (model 1): age, sex, body mass index, hypertension, diabetes mellitus, hyperlipidemia, chronic kidney disease, peripheral vascular disease, cerebrovascular event, smoking, anemia, previous PCI, previous heart failure, and the indication for the first index PCI. To ensure the robustness of our results, we constructed an additional model that incorporated contrast volume for PCI (model 2) and another model that excluded variables already used in the NCDR AKI risk score to mitigate the risk of overfitting due to overlapping variables (model 3). In models 1 and 3, there were 174 cases (2.2%) with missing data, while in model 2, 1,638 cases (20.7%) had missing data. We performed a complete case analysis for these models, and in the present analysis, we proceeded without multiple imputations due to the relatively small proportion of missing data in models 1 and 3. To examine whether the association of CA-AKI with subsequent MACE varied by baseline AKI risk, we tested an interaction between CA-AKI and risk categories. Additionally, to assess temporal changes in the incidence and prognosis of CA-AKI, we analyzed annual trends in CA-AKI incidence and contrast volume (2008-2021) to assess potential relationships between contrast usage practices and CA-AKI rates over time. Additionally, we divided the study period into 2 epochs: early period (≤2014) and late period (≥2015), corresponding with the middle year of this cohort. We constructed Cox models with an interaction term between CA-AKI status and time period and performed stratified analyses for each period separately. We examined the proportionality assumption using Schoenfeld residuals and found no instances where the assumption was violated. Analyses were performed using R version 4.2.3 (R Foundation for Statistical Computing), and a two-sided P value <0.05 threshold was used to determine statistical significance.
Results
Among the 7,916 patients, the mean age was 68.6 ± 11.8 years, 6,121 (77.3%) were men and 723 patients (9.1%) developed CA-AKI. The median follow-up duration was 2.0 years (mean: 1.8, Q1-Q3: 2.0-2.0, range: 0.0-2.0). Table 1 presents the baseline characteristics and procedural information, according to the occurrence of CA-AKI. Patients with CA-AKI were older and had a higher prevalence of heart failure, peripheral vascular disease, cerebrovascular events, hypertension, diabetes, chronic kidney disease, and a history of PCI.
Table 1.
Baseline Characteristics of Study Participants, Stratified by the Incidence of CA-AKI
| CA-AKI (n = 723) |
No CA-AKI (n = 7,193) |
Standardized Difference (Percentage Points) |
|
|---|---|---|---|
| Patient characteristics | |||
| Age (y), median (IQR) | 73.0 (64.0, 80.0) | 69.0 (61.0, 77.0) | 23.8 |
| Male, n (%) | 540 (74.7) | 5,581 (77.6) | 6.8 |
| Previous medical history | |||
| Myocardial infarction, n (%) | 97 (13.4) | 1,011 (14.1) | 1.9 |
| Heart failure, n (%) | 86 (11.9) | 539 (7.5) | 14.9 |
| Peripheral vascular disease, n (%) | 67 (9.3) | 533 (7.4) | 6.7 |
| Cerebrovascular event, n (%) | 78 (10.8) | 582 (8.1) | 9.2 |
| Hypertension, n (%) | 575 (79.5) | 5,193 (72.2) | 17.3 |
| Diabetes, n (%) | 318 (44.0) | 2,635 (36.6) | 15.0 |
| Hyperlipidemia, n (%) | 427 (59.1) | 4,450 (61.9) | 6.0 |
| Chronic kidney disease, n (%) | 263 (36.4) | 1,284 (17.9) | 42.6 |
| PCI, n (%) | 88 (12.2) | 1,266 (17.6) | 15.4 |
| Coronary artery bypass grafting, n (%) | 28 (3.9) | 289 (4.0) | 1.8 |
| Body mass index, median (IQR) kg/m2 | 23.5 (21.4, 26.0) | 23.8 (21.8, 26.1) | 11.5 |
| Smoking, n (%) | 254 (35.1) | 2,488 (34.6) | 2.4 |
| Anemia, n (%) | 252 (34.9) | 967 (13.4) | 51.7 |
| Heart failure on admission, n (%) | 200 (27.7) | 799 (11.1) | 42.8 |
| Clinical presentation | 59.4 | ||
| STEMI, n (%) | 428 (59.2) | 2,372 (33.0) | |
| NSTEMI/unstable angina, n (%) | 178 (24.6) | 2,147 (29.8) | |
| Chronic coronary syndrome, n (%) | 117 (16.2) | 2,674 (37.2) | |
| Cardiogenic shock, n (%) | 65 (9.0) | 276 (3.8) | 21.2 |
| Cardiac arrest, n (%) | 41 (5.7) | 161 (2.2) | 17.7 |
| Intra-aortic balloon pump, n (%) | 142 (19.6) | 392 (5.4) | 43.9 |
| Creatinine level, median (IQR), mg/dL | |||
| Before procedure | 1.00 (0.80, 1.30) | 0.90 (0.70, 1.10) | 30.9 |
| After procedure | 1.50 (1.10, 2.20) | 0.90 (0.80, 1.10) | 76.3 |
| Procedural characteristics | |||
| Access site | 20.4 | ||
| Radial | 398 (55.0) | 3,239 (45.0) | |
| Femoral | 318 (44.0) | 3,867 (53.8) | |
| Brachial | 7 (1.0) | 83 (1.2) | |
| Contrast volume, median (IQR), mL | 152.0 (115.8, 210.0) | 150.0 (110.0, 198.0) | 11.5 |
| Target vessel number | 19.5 | ||
| 1 vessel | 611 (84.5) | 6,534 (90.8) | |
| 2 vessels | 102 (14.1) | 593 (8.2) | |
| 3 vessels | 10 (1.4) | 65 (0.9) | |
| Lesion location | |||
| Left anterior descending artery | 416 (57.5) | 3,718 (51.7) | 12.0 |
| Right coronary artery | 200 (27.7) | 2,264 (31.5) | 8.7 |
| Left circumflex artery | 95 (13.1) | 1,098 (15.3) | 6.5 |
| Left main trunk | 34 (4.7) | 268 (3.7) | 5.4 |
CA-AKI = contrast-associated acute kidney injury; NSTEMI = non-ST-elevation myocardial infarction; PCI = percutaneous coronary intervention; STEMI = ST-elevation myocardial infarction.
Patients were then divided into 3 groups based on NCDR AKI risk tertiles, resulting in 2,591 (32.7%) in the low-risk group (predicted CA-AKI risk: 1.9%-4.9%), 2,723 (34.4%) in the intermediate-risk group (predicted CA-AKI risk: 4.9%-6.7%), and 2,602 (32.9%) in the high-risk group (predicted CA-AKI risk: ≥6.7%) (Supplemental Figure 1). The incidence of CA-AKI across these tertiles was 2.3%, 7.3%, and 17.9%. Supplemental Table 2 provides an overview of the baseline characteristics across these groups.
Association between the incidence of CA-AKI and two-year outcomes
Long-term clinical outcomes are presented in Table 2. The incidence of MACE was significantly higher in patients with CA-AKI (22.7% vs 10.6%, P < 0.001) than those without, largely driven by all-cause mortality (10.4% vs 3.7%, P < 0.001) and heart failure hospitalization (11.6% vs 4.0%, P < 0.001). The incidence rates of ACS and stroke were not significantly different (3.5% vs 3.0%, P = 0.59, and 2.2% vs 1.5%, P = 0.19).
Table 2.
Cumulative Incidence of Major Adverse Cardiovascular Events and Components at 2 Years by CA-AKI Status
| Outcome | CA-AKI (n = 723) Incidence Rate (95% CI)a |
No CA-AKI (n = 7,193) Incidence Rate (95% CI)a |
P Valuea |
|---|---|---|---|
| MACE | 22.7 (19.6, 25.7) | 10.6 (9.9, 11.3) | <0.001 |
| All-cause mortality | 11.2 (8.8, 13.6) | 4.1 (3.6, 4.5) | <0.001 |
| Acute coronary syndrome | 3.7 (2.3-5.2) | 3.3 (2.9-3.7) | 0.51 |
| Heart failure hospitalization | 12.5 (10.0-14.9) | 4.3 (3.8-4.8) | <0.001 |
| Stroke | 2.4 (1.2-3.6) | 1.6 (1.3-1.9) | 0.14 |
CA-AKI = contrast-associated acute kidney injury; MACE = major adverse cardiovascular events.
P values were calculated using the log-rank test for MACE and all-cause mortality and Gray test for acute coronary syndrome, heart failure hospitalization, and stroke.
Association between CA-AKI and two-year outcomes stratified by baseline risk profile
Kaplan-Meier curves regarding MACE were plotted and compared by log-rank tests for the entire cohort and within each risk group (Figure 2). Supplemental Figure 2 illustrates the Kaplan-Meier curves for death and the cumulative incidence curves for other individual MACE components (heart failure hospitalization, ACS, and stroke), with death treated as a competing event. Patients with CA-AKI experienced significantly higher rates of MACE and other adverse endpoints compared to those without CA-AKI in the entire cohort (log-rank P < 0.001). When stratified by CA-AKI risk profile, the association remained significant across all risk profiles, including the low-risk, intermediate-risk, and high-risk groups (Central Illustration).
Figure 2.
Kaplan-Meier Survival Estimates for MACE for All Patients and Stratified by CA-AKI Risk Groups
(A) Across the entire cohort, patients with CA-AKI had significantly higher incidence rates of MACE. (B and C) In the high- and intermediate-risk groups, patients with CA-AKI demonstrated significantly higher rates of MACE compared to patients without CA-AKI. (D) Within the low-risk group, no statistically significant difference was observed in long-term MACE. CA-AKI = contrast-associated acute kidney injury; MACE = major adverse cardiovascular events.
Central Illustration.
Study Design and Main Results
aHR = adjusted HR; other abbreviations as in Figures 1 and 2.
Table 3 presents the aHRs and 95% CIs describing the independent association of CA-AKI and MACE within each risk tertile. The association also remained significant in all risk groups (high-risk, aHR: 1.60; 95% CI: 1.30-1.98; intermediate-risk, aHR: 1.64; 95% CI: 1.10-2.44; and low-risk, aHR: 2.84; 95% CI: 1.43-5.65, respectively). The interactions between the primary outcome and AKI risk were not significant (P-interaction = 0.14), indicating a consistent effect of CA-AKI on MACE regardless of preprocedure CA-AKI risk. The Cox proportional hazards analysis adjusted for other models (models 2 and 3) also presented similar results, demonstrating the robustness of our findings (Supplemental Tables 3 and 4). The incidence rate of CA-AKI and the number of PCI procedures throughout the entire study period are shown in Supplemental Figure 3; the incidence rate of CA-AKI remained generally constant. CA-AKI was associated with increased MACE risk in both early periods (aHR: 1.46; 95% CI: 1.16-1.84; P = 0.001) and late periods (aHR: 2.08; 95% CI: 1.55-2.79; P < 0.0001). The interaction between CA-AKI and time period was not statistically significant (P-interaction = 0.21), indicating no significant change in CA-AKI's prognostic implication.
Table 3.
Multivariable-Adjusted Models Evaluating the Association Between CA-AKI and 2-Year Outcomes, Stratified by CA-AKI Risk Groups
| Model 1 | Adjusted HR | 95% CI | P Value |
|---|---|---|---|
| All patients (n = 7,742) | |||
| Major adverse cardiac events | 1.64 | 1.37-1.97 | <0.001 |
| All-cause mortality | 1.96 | 1.48-2.58 | <0.001 |
| Acute coronary syndrome | 1.06 | 0.68-1.64 | 0.81 |
| Heart failure hospitalization | 1.90 | 1.46-2.48 | <0.001 |
| Stroke | 1.44 | 0.83-2.51 | 0.19 |
| Low-risk group (n = 2,560) | |||
| Major adverse cardiac events | 2.84 | 1.43-5.65 | 0.003 |
| All-cause mortality | 3.96 | 1.37-11.5 | 0.011 |
| Acute coronary syndrome | 2.64 | 0.95-7.37 | 0.064 |
| Heart failure hospitalization | 4.85 | 1.28-18.4 | 0.020 |
| Stroke | NA | 0.00-Inf | 1.00 |
| Intermediate-risk group (n = 2,672) | |||
| Major adverse cardiac events | 1.64 | 1.10-2.44 | 0.015 |
| All-cause mortality | 1.76 | 0.90-3.46 | 0.10 |
| Acute coronary syndrome | 1.06 | 0.46-2.45 | 0.89 |
| Heart failure hospitalization | 2.99 | 1.58-5.64 | 0.001 |
| Stroke | 1.81 | 0.70-4.67 | 0.22 |
| High-risk group (n = 2,510) | |||
| Major adverse cardiac events | 1.60 | 1.30-1.98 | <0.001 |
| All-cause mortality | 1.89 | 1.38-2.59 | <0.001 |
| Acute coronary syndrome | 0.88 | 0.49-1.58 | 0.67 |
| Heart failure hospitalization | 1.69 | 1.27-2.25 | <0.001 |
| Stroke | 1.49 | 0.74-3.00 | 0.27 |
Adjusted for age, sex, body mass index, smoking, chronic kidney disease, hypertension, hyperlipidemia, diabetes mellitus, previous cerebrovascular disease, previous peripheral arterial disease, previous percutaneous coronary intervention, anemia, previous heart failure, and indication for the index percutaneous coronary intervention.
CA-AKI = contrast-associated acute kidney injury; NA = not applicable.
Discussion
Understanding the long-term risks associated with CA-AKI can be an important motivator for quality improvement efforts seeking to improve the safety of PCI. To better define these long-term risks, we examined the association of CA-AKI with 2-year MACE. Our main finding was that CA-AKI was associated with long-term MACE outcomes among all AKI risk profiles. These differences in MACE were primarily driven by increased risks for mortality and heart failure hospitalization, with a weaker association with ACS and stroke. When stratifying by CA-AKI risk, the association remained statistically significant across all risk profiles, including the low-risk group. Furthermore, there was no interaction between CA-AKI and 2-year MACE by preprocedural risk, suggesting that efforts to minimize CA-AKI should be undertaken for all patients undergoing PCI. Collectively, these results highlight that the current definition of CA-AKI, even if defined by a nominal increase in postprocedural creatinine, is associated with increased long-term risk for adverse clinical events and underscores the importance of CA-AKI prevention strategies.
Our study significantly extends the current understanding of the association between CA-AKI and outcomes. While many previous studies have focused on the immediate, in-hospital outcomes of patients, our research extends this prior work to describe the association of CA-AKI with long-term outcomes.20 In a large U.S. cohort, Tsai et al21 were able to show an increased rate of bleeding, recurrent myocardial infarction, and mortality during the initial PCI hospitalization. Similar findings of worse in-hospital events with CA-AKI during peripheral interventions have also been described.22 Mohebi et al15 investigated the association between CA-AKI and prognosis after 2 years, demonstrating that CA-AKI increased the mortality rate by 77%, an effect that was amplified by chronic kidney disease. This impact of CA-AKI on mortality is consistent with our current findings. Our analysis stratified by risk profile emphasizes that CA-AKI should not be underestimated even in low-risk groups. These findings indicate that CA-AKI is associated with worse long-term outcomes and highlight the potential importance of quality improvement efforts to reduce this periprocedural complication.
Another strength of this study is demonstrating the long-term association between CA-AKI and heart failure hospitalization following successful PCI. The speculated mechanisms through which CA-AKI exacerbates heart failure encompass myocardial damage from oxidative stress, activation of the renin-angiotensin-aldosterone system, fluid overload, acidemia, and uremia.23 In the era of PCI in patients with high-risk coronary artery disease, prioritizing the long-term risk of heart failure has become increasingly important.24 Consistent with prior research, our study demonstrated that patients with CA-AKI have a risk of heart failure that is approximately 2-fold higher than that of patients without CA-AKI.25,26 Our results advocate for management that concurrently acknowledges the risk of heart failure in high-risk individuals, thus substantiating the necessity for outpatient care that is attuned to the potential onset of heart failure.
Importantly, patients who develop CA-AKI have a number of risk factors that are also associated with worse long-term outcomes,15,27,28 and it is not possible to exclude the possibility that developing CA-AKI is more of a marker than a mediator of worse long-term events. Arguing against this, however, is that there remained an independent association between CA-AKI and subsequent clinical events after multivariable adjustment and within CA-AKI risk groups where these risk factors are more balanced. The relationship suggests that similar insights can be advocated across all risk groups, as the interaction term between CA-AKI and MACE 2 years later was not significant in any risk group. The aHR for CA-AKI was numerically highest in the low-risk group, despite no significant interaction across risk strata. This finding suggests that, despite having fewer traditional risk factors, patients deemed “low-risk” should not be overlooked. When CA-AKI does occur in this population, it may confer a relatively large adverse implication on long-term outcomes, underscoring the importance of maintaining vigilance for all patients undergoing PCI, even those classified as low-risk. The findings of this study, using the NCDR AKI risk score, can be prospectively implemented in clinical settings using the NCDR AKI bedside risk score, which has been updated to include “safe contrast limits” to reduce CA-AKI risk by preprocedural AKI risk.29 Further works to implement these tools are needed.
Our study results emphasize the persistent association between CA-AKI and long-term outcomes across all risk scores, suggesting comprehensive clinical assessment should be universally applied. Our observation that even patients with low preprocedural risk showed significant associations between CA-AKI and subsequent MACE extends previous work, such as the cluster-randomized study by James et al10 that demonstrated reduced adverse outcomes with the NCDR risk model implementation, which excluded patients with predicted AKI risk below 5%. The substantial potential for AKI prevention, as shown by Canadian research where NCDR risk model use substantially reduced AKI incidence, should inspire wider implementation of CA-AKI reduction strategies.30,31 Despite developing various risk models potentially affecting clinical practice, current cardiovascular guidelines do not adequately incorporate risk stratification into standard clinical protocols.32, 33, 34 Future clinical trials incorporating real-world implementation of risk models may advance our understanding beyond the current evidence surrounding CA-AKI prevention. These findings should motivate such efforts and refute perceptions that CA-AKI is not an important outcome to address.
Study Limitations
Our study has several potential limitations. First, as an observational study, there is always a risk for unmeasured confounding, even though we adjusted for many possible confounding factors, including those identified in prior studies. Second, this cohort may not have had sufficient event numbers for ACSs or strokes and may have lacked enough power to detect these outcomes. Longer follow-up and larger studies would help support the observed associations. Third, this registry includes a subset of Japanese hospitals, and its generalizability throughout Japan or worldwide is unknown. Fourth, we did not systematically collect long-term renal outcomes such as progression to end-stage renal disease or dialysis initiation, as the JCD-KiCS registry primarily focuses on cardiovascular outcomes. This limitation prevents us from fully elucidating whether CA-AKI acts as an intermediate factor leading to poor outcomes through renal disease progression or is merely a marker of systemic vulnerability. Analysis of such renal endpoints could have provided additional insights into the causal pathway between CA-AKI and subsequent MACE. Fifth, this study has no information on the types of contrast used during PCI, and data regarding the administration of contrast through other modalities, such as contrast computed tomography, have not been considered. Sixth, we performed a complete case analysis without multiple imputations for missing data. While this approach is straightforward and preserves the original characteristics of the data, it may introduce bias if data are not missing completely at random. Finally, there is a slight difference in defining postprocedural creatinine between the JCD-KiCS and NCDR CathPCI registries. In the United States, this value is defined as the highest measurement during the hospitalization after the procedure. Conversely, the JCD-KiCS registry extracts this highest value throughout the 30-day follow-up period. Given that creatinine typically peaks 3 to 5 days postcontrast administration,35 our registry's approach minimizes the possibilities of underestimating the true incidence of CA-AKI.
Conclusions
Our study demonstrates a strong and independent association between the incidence of CA-AKI and long-term clinical outcomes. This finding underscores the importance of proactive quality improvement efforts to reduce the incidence of CA-AKI. Integrated, patient-centered approaches to improve long-term outcomes by tailoring preventive strategies to risk are a promising strategy to mitigate CA-AKI and potentially improve the long-term outcomes of patients undergoing PCI.
Perspectives.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: In light of the potential long-term benefits of preventing CA-AKI, aggressive quality improvement efforts, likely targeting preprocedural hydration and tailoring contrast limits to risk, are needed and should be prioritized to improve the safety of all patients requiring PCI.
TRANSLATIONAL OUTLOOK: CA-AKI is not merely a transient periprocedural complication but can have serious, prolonged risks, reinforcing the need to refine risk models that facilitate early detection and targeted intervention. Incorporating novel biomarkers and refined decision support tools into routine PCI practice may help clinicians personalize strategies to reduce CA-AKI.
Funding support and author disclosures
The article processing charge in this study were supported by a Grant-in-Aid for Young Scientists (Japan Society for the Promotion of Science KAKENHI; 22K16067). This research was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (KAKENHI No. 20H03915). Dr Kohsaka has received speaker fees from Pfizer and has received institutional research grant support from AstraZeneca. The funders did not play a role in the study design, data collection, data analysis, publication decision, or manuscript preparation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Acknowledgments
The authors appreciate the contributions of all the investigators and clinical coordinators involved in the JCD-KiCS registry.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For supplemental tables and figures, please see the online version of this paper.
Supplemental data
References
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