Early detection of contrast-associated acute kidney injury after coronary angiography: A predictive value of osteopontin

Abstract

BACKGROUND

Contrast-associated acute kidney injury (CA-AKI) is a common and serious complication of percutaneous coronary intervention (PCI). It is linked to higher rates of morbidity and mortality. Early detection of patients at risk is crucial for implementing timely preventive actions. Osteopontin (OPN), a multifunctional glycoprotein highly expressed in kidney tissue, has been suggested as a potential biomarker for AKI. However, its role in CA-AKI remains unclear.

AIM

To evaluate the predictive value of serum OPN levels for early identification of CA-AKI in patients undergoing PCI and to compare its diagnostic performance with the Mehran risk score and traditional clinical predictors.

METHODS

A prospective, non-randomized comparative study was conducted at Assiut University Hospitals between March 2023 and March 2024. A total of 155 patients who underwent elective or primary PCI were enrolled. Exclusion criteria included chronic kidney disease, prior CA-AKI, cardiogenic shock, obstructive uropathy, malignancy, or nephrotoxic drug use. Serum OPN was measured immediately before and after PCI by ELISA alongside routine renal function tests. CA-AKI was defined as ≥ 0.3 mg/dL absolute or ≥ 50% relative rise in serum creatinine within 7 days post-contrast. The primary outcomes were the rate of CA-AKI after PCI and changes in OPN levels. Patients with CA-AKI were compared with patients without CA-AKI. Logistic regression and receiver operating characteristic curve analyses were performed to assess predictors and diagnostic accuracy.

RESULTS

CA-AKI occurred in 20 patients (12.9%). These patients were significantly older (59.54 ± 8.67 years) than those without CA-AKI (48.19 ± 7.89 years; P < 0.001). Patients with CA-AKI had significantly higher OPN levels before and after PCI compared with those without CA-AKI (P < 0.001). Independent predictors of CA-AKI included pre-PCI OPN [odds ratio (OR) = 3.22], post-PCI OPN (OR = 2.90), contrast volume (OR = 1.22), and Mehran score (OR = 3.10). Pre-PCI OPN > 69.6 ng/mL demonstrated 86.8% accuracy (area under the curve of 0.80). Combining OPN with the Mehran score produced a diagnostic accuracy of 88% (area under the curve of 0.95).

CONCLUSION

Elevated OPN levels, both before and after PCI, independently predicted CA-AKI and enhanced the predictive power of the Mehran score. Routine assessment of OPN may provide an effective strategy for early risk stratification in patients undergoing PCI.

Key Words: Acute kidney injury; Contrast; Contrast-associated acute kidney injury; Coronary angiography; Nephropathy; Osteopontin

Core Tip: Serum osteopontin (OPN) is a strong and independent biomarker for predicting contrast-associated acute kidney injury after percutaneous coronary intervention. Its combination with the Mehran risk score offers the highest diagnostic accuracy. The current study presented novel evidence that OPN levels, measured before and after percutaneous coronary intervention, were significantly elevated in patients with contrast-associated acute kidney injury, identifying OPN as a robust and independent predictor (alongside the Mehran score and contrast volume). Integrating OPN with the Mehran score yielded a diagnostic accuracy of 88%, suggesting that OPN should be incorporated into risk stratification strategies for timely preventive interventions.

INTRODUCTION

Percutaneous coronary intervention (PCI) is a widely performed diagnostic and therapeutic procedure that requires the administration of iodinated contrast media[1,2]. Despite advances in contrast formulation and periprocedural care, contrast-associated acute kidney injury (CA-AKI) remains a frequent and clinically significant complication of PCI. It is associated with increased morbidity, prolonged hospitalization, and higher mortality[1,3].

The reported incidence of CA-AKI varies widely due to differences in diagnostic criteria, patient risk profiles, and procedural characteristics. Established risk factors include advanced age, diabetes mellitus, baseline renal dysfunction, hemodynamic instability, and higher contrast volume. Early identification of patients at high risk is therefore essential to enable timely preventive strategies and improve clinical outcomes[2,4].

Osteopontin (OPN) is a multifunctional glycoprotein involved in inflammatory signaling and tissue remodeling[5,6]. The kidney exhibits high OPN expression, particularly in the loop of Henle and the distal tubules. OPN may signal various biological pathways in AKI[5,7] with rapid upregulation in response to acute tubular and ischemia-reperfusion injuries, oxidative stress, and inflammatory activation[5,8,9]. Experimental and clinical studies have demonstrated elevated circulating and urinary OPN levels in AKI of diverse etiologies with levels correlating with injury severity and adverse outcomes[10-12]. These findings suggest a dual role for OPN, acting both as a mediator and a biomarker of AKI.

The literature may definitively establish the clinical utility of OPN as a reliable biomarker for various biological activities and diseases, including CA-AKI[13-15]. OPN has been extensively studied for its role in surgeries, inflammatory diseases, malignancy, and nephrotoxicity, revealing its potential as a valuable biomarker for monitoring inflammation and metabolic disorders[7,14]. Additionally, OPN plays a crucial role in bacterial infections in which it can prevent bacterial adhesion[16,17].

In contrast to other biomarkers used for CA-AKI, the evidence for OPN in CA-AKI is limited with only a few experimental and clinical studies suggesting its potential utility[10,18,19]. However, small sample sizes, heterogeneous patient populations, inconsistent biomarker measurements, lack of prospective design, inconsistent timing of OPN measurement, limited validation of predictive ability, absence of integration with clinical scores, and limited data in PCI and CA-AKI settings are among the shortcomings identified in the previous studies[20-22].

The present study addressed most of these gaps by providing prospective data on OPN levels in patients exposed to iodinated contrast, evaluating its association with subsequent renal impairment, and comparing it with existing predictors.

MATERIALS AND METHODS

Study design

A prospective non-randomized comparative study was conducted at the Department of Cardiology and Department of Internal Medicine, Assiut University Hospitals (Egypt), from March 2023 to March 2024. The aim was to identify the predictors of CA-AKI after PCI with specific evaluation of the role of serum OPN.

Patient selection

Any patient aged 18 years or older who was scheduled for primary or elective PCI was eligible for the study. Exclusion criteria included a history of previous CA-AKI, chronic kidney disease, cardiogenic shock, congestive heart failure, obstructive uropathy, malignancy, and recent exposure to nephrotoxic agents.

Based on the previously reported frequency of CA-AKI of 4%-15%[3], a total of 155 patients who underwent PCI were recruited to achieve the minimum sample size. The sample size was calculated using OpenEpi version 3 with the following assumptions: 5% alpha error; 80% power of the study; and a 95% confidence interval.

Clinical assessments

Full history and clinical examination included general, chest, cardiac, neurological, and lower limb examinations. A comprehensive medical profile was obtained from all subjects, including age, sex, diabetes mellitus, hypertension, body mass index, previous PCI, and smoking.

The following laboratory data were obtained within 24 h before PCI: Complete blood count; serum creatinine; urea; random blood sugar; and hepatitis serology. Additionally, the glomerular filtration rate was calculated using the EPI-CKD equation[23].

Also, an abdominal ultrasound was performed to assess the echogenicity of the kidneys and the presence of obstructive uropathy, using a real-time electronic 3.75 MHz convex-type scanner attached to a high-resolution ultrasound machine (Aplio; Toshiba Medical Systems Corporation, Tochigi, Japan). Additionally, a 12-lead electrocardiogram was performed in all patients.

Echocardiography was performed on all patients in B-mode using the Siemens ACUSON X700 scanner (Siemens, Germany) and a 2.5 MHz transducer. This intervention followed the guidelines of the American Society of Echocardiography. End-diastolic and end-systolic left ventricle volumes were measured using a two-dimensional reference sector according to Simpson’s method. Left ventricle ejection fraction was calculated using standard methods.

Mehran risk score: The Mehran risk score is a clinical tool used to predict the risk of contrast-induced nephropathy (CIN) after PCI or cardiac catheterization[24]. Based on the total score, patients were classified into: Low risk (approximately 7.5% risk of CIN) in the range of 0-5 points; moderate risk (approximately 14% risk of CIN) in the range of 6-10 points; high risk (approximately 26% risk of CIN) in the range of 11-15 points; and very high risk (approximately 57% risk of CIN) with scores ≥ 16 points.

Measurement of OPN level: OPN was measured by OPN-ELISA (TX, United States). The kit is a sandwich ELISA for in vitro quantitative measurement of OPN in human serum.

Timing of blood testing: All blood tests were performed immediately before the angiographic procedure through a centrally placed vascular access sheath. However, serum creatinine, blood urea nitrogen, and OPN were measured directly before and after the angiographic procedure. The change of serum creatinine level was monitored for 7 days after the procedure.

The CA-AKI was defined as an absolute increase of ≥ 0.3 mg/dL or a ≥ 50% relative increase in serum creatinine after coronary angiography. This level was compared with the preprocedural serum creatinine level. The time was defined as within 7 days after the coronary angiography procedure to avoid missing late CA-AKI when no alternative etiology for AKI was identified[25].

Study outcomes

The primary outcomes were the rate of CA-AKI after coronary angiography and the change in the pre-angiography and post-angiography OPN serum levels up to 7 days after the procedure.

Ethical approval

This prospective study was approved by the Ethics Committee of the Faculty of Medicine, Assiut University (Approval No. 17200785). Additionally, it was registered in Clinical Trials under the number NCT05547581. Written consent was obtained from patients for participation in the study.

Statistical analysis

Data were summarized by mean ± SD for numerical data and by n (%) for categorical data. The significance of the difference was calculated using the χ² test and Student’s t test. The correlation between OPN and variables was determined using Pearson correlation.

Logistic regression analysis was used to assess possible predictors of CA-AKI. In addition, the receiver operator characteristics curve was used to determine the optimal cutoff point of the OPN/Mehran score for predicting CA-AKI. A cutoff value of less than 0.05 was considered for the probability of chance with a 95% confidence interval. All statistical tests were done by IBM SPSS version 20.

RESULTS

Baseline and clinical characteristics

The study observed two significant differences between the CA-AKI group and the non-CA-AKI group in terms of baseline data and clinical findings. As in Table 1, the CA-AKI group had a significantly higher mean age compared with the non-CA-AKI group (P < 0.001). The patients with CA-AKI presented with significantly higher glycosylated hemoglobin A1c levels (P = 0.01). Otherwise, both groups were comparable in the baseline data, drug intake, clinical findings, laboratory results, and electrocardiogram findings (Tables 1 and 2).

Table 1 Baseline demographic and clinical characteristics of the studied group based on the development of contrast-associated acute kidney injury.

Variables	CA-AKI (n = 20)	Non-CA-AKI (n = 135)	P value
Age (years)	59.54 ± 8.67	48.19 ± 7.89	0.001
Sex
Male	15 (75.0)	95 (70.4)	0.984
Female	5 (25.0)	40 (29.6)
BMI (kg/m2)	24.60 ± 4.40	25.77 ± 3.11	0.870
Smoking	4 (20.0)	20 (14.8)	0.756
Diabetes mellitus	14 (70.0)	100 (74.0)	0.772
Hypertension	6 (35.0)	40 (29.6)	0.161
Chest pain			0.094
Typical	15 (75.0)	108 (80.0)
Atypical	5 (25.0)	27 (20.0)
Heart rate (beats/minute)	80.46 ± 15.51	82.11 ± 15.98	0.343
DBP (mmHg)	90.90 ± 6.78	89.11 ± 8.91	0.304
SBP (mmHg)	118.56 ± 9.34	117.78 ± 14.78	0.882
ECG findings			0.092
Anterior infarction	16 (80.0)	108 (80.0)
Inferior infarction	2 (10.0)	15 (11.1)
Posterolateral infarction	2 (10.0)	12 (8.9)
Prior PCI	3 (15.0)	20 (14.8)
Drug intake			0.342
ACE inhibitors	8 (40.0)	50 (37.0)	0.650
ARBs	4 (20.0)	35 (26.0)	0.390
Beta blocker	16 (80.0)	108 (80)	0.090
Loop diuretics	6 (30.0)	41 (30.4)	0.210
Nitrates	10 (40.0)	55 (40.7)	0.780
CCB	5 (25.0)	34 (25.2)	0.570
Statins	16 (80.0)	110 (81.5)	0.070
Aspirin	17 (85.0)	115 (85.2)	0.330
MRA	2 (10.0)	15 (11.1)	0.710

Data are presented as mean ± SD or n (%). BMI: Body mass index; DBP: Diastolic blood pressure; SBP: Systolic blood pressure; ECG: Electrocardiogram; PCI: Percutaneous coronary intervention; ACE: Angiotensin-converting enzyme; CCB: Calcium channel blocker; MRA: Mineralocorticoid receptor antagonist; CA-AKI: Contrast-associated acute kidney injury; ARBs: Angiotensin II receptor blockers.

Table 2 Laboratory findings in both groups of patients based on acute kidney injury.

Variables	CA-AKI (n = 20)	Non-CA-AKI (n = 135)	P value
Blood count
Hb (g/dL)	11.25 ± 1.97	11.16 ± 1.26	0.349
Leucocytes (103/μL)	9.86 ± 4.57	7.75 ± 5.43	0.098
Platelets (103/μL)	209.05 ± 74.13	192.94 ± 98.51	0.238
Kidney function tests
Serum creatinine (mg/dL)	1.12 ± 0.09	1.09 ± 0.10	0.176
Urea (mg)	9.24 ± 2.17	8.18 ± 6.89	0.582
eGFR (mL/minute/1.73 m2)	99.84 ± 3.41	97.77 ± 2.65	0.092
Liver function tests and markers
ALT (U/L)	22.28 ± 6.11	25.70 ± 8.01	0.251
AST (U/L)	23.46 ± 8.85	26.23 ± 9.15	0.972
Bilirubin (mg/dL)	0.71 ± 0.04	0.78 ± 0.02	0.221
Albumin (g/dL)	3.78 ± 0.48	3.80 ± 0.49	0.923
Positive HCV antibodies	0	2 (1.5)	0.542
Positive HBsAg	1 (5.0)	1 (0.8)	0.813
Glycosylated Hb (%)	8.38 ± 0.98	6.45 ± 0.72	0.010
Lipid profile
Cholesterol (mg/dL)	197.60 ± 37.16	171.93 ± 29.28	0.563
HDL (mg/dL)	45.64 ± 12.21	54.32 ± 15.89	0.432
LDL (mg/dL)	103.79 ± 34.78	95.13 ± 24.38	0.670
Triglyceride (mg/dL)	152.39 ± 54.46	144.36 ± 35.40	0.581
Cardiac markers
Troponin (ng/mL)	8.11 ± 2.22	7.46 ± 3.30	0.762
Creatine kinase (U/L)	568.98 ± 123.78	501.23 ± 189	0.112
CK-MB (ng/mL)	15.55 ± 2.19	14.90 ± 3.19	0.118

Data are presented as mean ± SD or n (%). eGFR: Estimated glomerular filtration rate; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HCV: Hepatitis C virus; HBsAg: Hepatitis B virus surface antigen; Hb: Hemoglobin; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; CK-MB: Creatine kinase MB; CA-AKI: Contrast-associated acute kidney injury.

Procedural and marker differences

In Figure 1 and Tables 3 and 4, significant differences were observed in both the key biomarker and procedural factors. OPN levels were significantly higher in the CA-AKI group (P < 0.001). Furthermore, the amount of contrast used during the procedure in the CA-AKI group was significantly higher than in the non-CA-AKI group (P < 0.001). Echocardiography and angiographic data did not show significant differences between the two groups.

Figure 1 Mean osteopontin levels in patients based on the incidence of contrast-associated acute kidney injury before and after percutaneous coronary intervention. CA-AKI: Contrast-associated acute kidney injury; PCI: Percutaneous coronary intervention; SD: Standard deviation.

Table 3 Kidney function and osteopontin levels before and after the percutaneous coronary intervention in both groups of patients.

Variables	CA-AKI (n = 20)	Non-CA-AKI (n = 135)	P value
Serum creatinine (mg/dL)
Before	1.12 ± 0.09	1.09 ± 0.10	0.170
After	1.89 ± 0.33	1.08 ± 0.18	0.001
Urea (mg)
Before	9.24 ± 2.17	8.18 ± 6.89	0.589
After	23.33 ± 5.66	7.54 ± 3.98	0.001
eGFR (mL/minute/1.73 m2)
Before	99.84 ± 3.41	97.77 ± 2.65	0.093
After	79.55 ± 7.99	99.11 ± 12.11	0.001
Osteopontin (ng/mL)
Before	76.11 ± 5.68	22.90 ± 9.19	0.001
After	89.56 ± 14.56	33.22 ± 8.56	0.001

Data are presented as mean ± SD. eGFR: Estimated glomerular filtration rate; CA: Contrast-associated; AKI: Acute kidney injury.

Table 4 Echocardiography and angiographic data of both groups.

Variables	CA-AKI (n = 20)	Non-CA-AKI (n = 135)	P value
Echocardiography
Aortic valve area (cm)	2.91 ± 0.45	2.89 ± 0.37	0.113
LVEDD (cm)	4.73 ± 0.60	5.07 ± 0.93	0.309
LVESD (cm)	3.53 ± 0.93	3.49 ± 0.72	0.750
Ejection fraction (%)	54.03 ± 3.78	55.43 ± 5.40	0.262
PASP (mmHg)	29.11 ± 2.56	28.90 ± 3.81	0.209
LV diastolic dysfunction	3 (15.0)	12 (8.9)	0.458
Type of PCI			0.230
Elective	16 (80.0)	110 (81.5)
Primary	4 (20.0)	25 (18.5)
Access			0.873
Femoral access	17 (85.0)	125 (92.6)
Radial access	3 (15.0)	10 (7.4)
Type of contrast			0.870
Scanlux	16 (80.0)	110 (81.5)
Ultravist	3 (15.0)	20 (14.8)
Telebrix	1 (5.0)	5 (3.7)
Amount of contrast (mL)	158.99 ± 29.88	112.94 ± 25.95	0.001
Killip classes > II	7 (35.0)	41 (30.4)	0.582
Culprit lesion			0.708
LAD	15 (75.0)	100 (74.0)
RCA	3 (15.0)	20 (14.8)
LCx	2 (10.0)	8 (6.0)
Oblique marginal	0	7 (5.2)

Data are presented as mean ± SD or n (%). LVEDD: Left ventricular end diastolic diameter; LVESD: Left ventricular end systolic diameter; PASP: Pulmonary artery systolic pressure; LV: Left ventricle; PCI: Percutaneous coronary intervention; LAD: Left anterior descending artery; RCA: Right coronary artery; LCx: Left circumflex artery; CA-AKI: Contrast-associated acute kidney injury.

Risk score and correlations

In Tables 5 and 6, the CA-AKI group demonstrated a significantly higher mean Mehran risk score compared with the non-CA-AKI group (P < 0.001). Consequently, the risk stratification was markedly different: The patients with CA-AKI were predominantly in the moderate (5%), high (70%), and very high (25%) risk categories while 85.2% of the patients without CA-AKI were in the low-risk category.

Table 5 Mehran risk scores of enrolled patients in both groups.

Variables	CA-AKI (n = 20)	Non-CA-AKI (n = 135)	P value
Total score	14.11 ± 3.48	4.90 ± 1.23	0.001
Class			0.001
Low risk	0	115 (85.2)
Moderate risk	1 (5.0)	20 (14.8)
High risk	14 (70.0)	0
Very high risk	5 (25.0)	0

Data are presented as mean ± SD or n (%). CA-AKI: Contrast-associated acute kidney injury.

Table 6 Correlations of osteopontin levels with other variables.

Variables	Before PCI		After PCI
	r	P value	r	P value
Age (years)	0.04	0.980	0.11	0.870
Body mass index (kg/m2)	0.10	0.450	0.09	0.270
SBP (mmHg)	-0.05	0.620	-0.08	0.470
DBP (mmHg)	-0.19	0.090	-0.09	0.390
Hemoglobin (g/dL)	-0.06	0.560	-0.02	0.840
Leucocytes (103/μL)	0.11	0.560	0.13	0.490
Platelets (103/μL)	0.09	0.200	-0.10	0.510
Serum creatinine (mg/dL)	0.45	0.001	0.42	0.001
Blood urea (mg)	0.23	0.040	0.30	0.020
eGFR (mL/minute/1.73 m2)	-0.33	0.030	-0.42	0.001
Alanine aminotransferase (U/L)	0.08	0.120	-0.11	0.890
Aspartate aminotransferase (U/L)	0.09	0.120	0.19	0.110
Bilirubin (mg/dL)	0.11	0.310	0.01	0.070
Albumin (g/dL)	0.21	0.560	-0.07	0.090
Glycosylated hemoglobin (%)	0.10	0.190	0.21	0.610
Cholesterol (mg/dL)	0.05	0.650	0.14	0.200
High-density lipoprotein (mg/dL)	0.14	0.210	0.24	0.400
Low-density lipoprotein (mg/dL)	-0.13	0.230	0.01	0.990
Triglyceride (mg/dL)	0.21	0.060	0.06	0.580
Troponin (ng/mL)	0.11	0.090	0.07	0.100
Creatine kinase (U/L)	0.09	0.100	0.11	0.380
CK-MB (ng/mL)	0.04	0.220	0.10	0.180
Aortic valve area (cm)	0.04	0.690	0.01	0.900
LVEDD (cm)	-0.01	0.870	-0.21	0.060
LVESD (cm)	0.12	0.560	0.09	0.760
Ejection fraction (%)	-0.18	0.210	-0.11	0.590
PASP (mmHg)	0.18	0.450	0.17	0.110
Amount of contrast (mL)	0.20	0.090	0.11	0.210
Mehran score	0.45	< 0.001	0.47	< 0.001

Data are presented as mean ± SD or n (%). SBP: Systolic blood pressure; DBP: Diastolic blood pressure; eGFR: Estimated glomerular filtration rate; CK-MB: Creatine kinase MB; PASP: Pulmonary artery systolic pressure; LVEDD: Left ventricular end diastolic pressure; LVESD: Left ventricular end systolic pressure; PCI: Percutaneous coronary intervention.

The analysis revealed a clear relationship between the new biomarker and kidney function. It showed that serum OPN had positive correlations with blood urea and creatinine and a negative correlation with the glomerular filtration rate. Critically, OPN also had a strong positive correlation with the Mehran score (Table 6).

Predictors and diagnostic accuracy

The multivariable regression analysis identified the independent predictors for CA-AKI after PCI: OPN levels before PCI [odds ratio (OR) = 3.22], OPN levels after PCI (OR = 2.90), the amount of dye used (OR = 1.22), and the Mehran score (OR = 3.10; Table 7). Finally, Figure 2 and Table 8 demonstrated the diagnostic superiority of the combined model. The combined Mehran score with OPN before PCI achieved the best diagnostic accuracy for predicting CA-AKI at 88%.

Figure 2 Accuracy of osteopontin and Mehran score in the prediction of contrast-associated acute kidney injury after percutaneous coronary intervention. OPN: Osteopontin; PCI: Percutaneous coronary intervention.

Table 7 Predictors of contrast-associated acute kidney injury in all patients.

Predictors	Odds ratio	95%CI	P value
Age (years)	1.21	1.30-7.89	0.434
Glycosylated hemoglobin (%)	1.45	0.98-3.11	0.983
OPN before PCI	3.22	2.56-8.18	0.001
OPN after PCI	2.90	2.11-5.66	0.001
Contrast amount	1.22	1.09-2.33	0.012
Mehran score	3.10	2.22-7.89	0.001

OPN: Osteopontin; PCI: Percutaneous coronary intervention; CI: Confidence interval.

Table 8 Accuracy of osteopontin and Mehran score in prediction of contrast-associated acute kidney injury.

Indices	OPN before PCI	OPN after PCI	Mehran score	Mehran score with OPN before PCI	Mehran score with OPN after PCI
Sensitivity	89.0%	82.0%	85.0%	91.0%	86.0%
Specificity	85.0%	79.0%	83.0%	88.0%	82.0%
PPV	82.3%	75.5%	43.0%	53.1%	41.0%
NPV	90.8%	84.6%	97.0%	98.0%	97.0%
Accuracy	86.8%	80.3%	83.3%	88.0%	82.0%
Cutoff point	> 69.56	> 75.00	> 16.00
AUC	0.80	0.70	0.80	0.95	0.80
P value	0.001	0.001	0.001	0.001	0.001

PPV: Positive predictive value; NPV: Negative predictive value; AUC: Area under the curve; OPN: Osteopontin; PCI: Percutaneous coronary intervention.

DISCUSSION

Although several animal studies have explored its involvement in contrast-induced renal injury, the role of OPN in the acute setting of human CA-AKI has not yet been verified[20-22]. The present study addressed this knowledge gap by providing prospective data on serum OPN levels in patients exposed to iodinated contrast, assessing its association with subsequent renal impairment, and comparing its performance with that of established predictive markers.

A total of 155 patients were enrolled in the study and scheduled for PCI. Only 20 (12.9%) patients developed CA-AKI. In the current study, the frequency of CA-AKI was similar to the previously reported rate that ranged from 4% to 15%[3,26-28]. Differences in the definitions and patient characteristics may explain the variable incidence of CA-AKI reported in the literature. It is uncertain whether this heterogeneity depends on study differences or improvements in CA-AKI prevention.

Age impact

Ye et al[29] reported that patients with CA-AKI were more likely to be older and female and have comorbidities such as hypertension, diabetes, and previous heart failure. Unexpectedly, smoking and a family history of coronary artery disease were associated with a lower risk of CA-AKI. Hence, they recommended conducting further studies on these factors[29]. Similarly, the current study found that the CA-AKI group had a significantly higher mean age. Other demographic data were comparable in the two groups. This finding was consistent with a previous study that revealed that patients with CA-AKI were older than those with other conditions[28].

The current study revealed that both groups had comparable clinical, laboratory, and electrocardiogram findings, except for significantly higher glycosylated hemoglobin A1c among patients with CA-AKI. Similarly, previous studies have also reported that patients with significant glycemic fluctuations can impair vascular endothelial function, increase inflammation levels, and subsequently cause renal artery injury, leading to CA-AKI[30,31].

One of the main findings in the current study was that the CA-AKI group had significantly higher OPN levels. Lorenzen et al[11] reported that patients who were critically ill and had AKI had higher OPN concentrations than patients who are critically ill and did not have AKI[11]. In another study, plasma OPN levels were significantly higher in patients with AKI when compared with healthy controls. The plasma OPN levels were higher in the non-survivor AKI group than in the survivor AKI group, suggesting it is associated with the injury. Also, it was found that there was an increase in mean OPN levels in the septic group of AKI in comparison with the non-septic AKI group[12].

Mehran scores

The current results demonstrated a clear association between higher Mehran scores and the development of CA-AKI. Patients with CA-AKI exhibited significantly elevated mean Mehran scores compared with those without CA-AKI. This indicated that the Mehran score is a reliable predictor of CA-AKI.

The stratification of risk further highlights this relationship. Among patients with CA-AKI, 70% were classified as high risk and 25% as very high risk, whereas patients who did not develop CA-AKI predominantly fell into the low-risk category (85.2%). This distribution underscores the utility of the Mehran risk score not only as a continuous measure but also as a categorical tool for risk stratification. The Mehran score remained a strong predictor, integrating clinical and procedural risk factors and reinforcing its utility in stratifying patients at risk for CA-AKI[24].

These findings are consistent with previous studies[4,24]. These studies have validated the Mehran score for predicting CA-AKI after contrast exposure. This score was originally proposed to integrate both patient-specific factors (e.g., baseline renal function, diabetes, hypotension) and procedural variables (e.g., contrast volume, use of an intra-aortic balloon pump) to quantify risk[4,24].

Contrast volume

PCI access and the number of stents were not different between the studied groups. Similar findings have been reported in previous studies[32-34]. The current study revealed that the amount of contrast used during the procedure was significantly higher in the CA-AKI group than in the non-CA-AKI group. Abdel Hammed et al[32] reported that the amount of intra-arterial dye was significantly higher in patients with CA-AKI compared with those without CA-AKI. The amount of contrast dye was associated with a modest but significant risk. In contrast, Schwab et al[35] did not show any significant differences in nephrotoxic effect between several contrast media[35].

Yuan et al[36] observed that there was no statistical significance in the proportion of patients with contrast volume > 200 mL between the CI-AKI and non-CI-AKI groups[36]. The popularization of nonionic, iso-osmolar contrast media, combined with the use of the lowest volume, may explain the inconsistency. However, a more plausible explanation is the presence of other factors that contribute more to the development of AKI than contrast media[37].

Although no statistically significant difference was observed regarding the type or osmolarity of contrast media in the current study, the osmotic pressure of contrast agents is clinically relevant to nephrotoxicity[32-34]. High-osmolarity and low-osmolarity contrast media have been shown to induce renal vasoconstriction, medullary hypoxia, and direct tubular epithelial toxicity through osmotic stress, increased viscosity, and oxidative injury[32-34].

Even iso-osmolar agents may contribute to renal injury in susceptible patients by increasing tubular workload and intratubular pressure, particularly in the setting of reduced renal reserve or systemic inflammation[33,34]. Therefore, the lack of statistical significance in this cohort does not preclude a pathophysiological role of contrast osmolarity in patients with CA-AKI. However, this may reflect a limited sample size or relatively uniform contrast use across the study groups[32,34].

OPN predictive values

In the current study several independent predictors for CA-AKI were identified in patients undergoing PCI. Specifically, the levels of OPN, the amount of contrast dye administered, and the Mehran score were all significantly associated with the development of CA-AKI. Pre-procedural OPN emerged as a particularly strong predictor, indicating that patients with elevated baseline OPN levels were more than three times as likely to develop CA-AKI. Post-procedural OPN also retained predictive value, reflecting the ongoing renal insult or inflammatory response following contrast exposure. This finding was consistent with the literature[6,29].

Diagnostic performance analysis revealed that OPN levels provided substantial predictive accuracy. Both pre-PCI and post-PCI OPN levels provided high diagnostic accuracy at certain cutoff values in the current study. This highlights the potential of OPN as a biomarker for the early identification of patients at risk, enabling timely preventive interventions[2,11,12].

These findings align with the growing body of literature supporting the role of biomarkers in predicting CA-AKI[11,33,36]. OPN is involved in inflammation, oxidative stress, and renal injury. It has been increasingly recognized as an early indicator of renal tubular damage[5,8,9].

Notably, the observation of elevated pre-procedural OPN levels suggests that OPN may serve as a marker of underlying vulnerability before contrast exposure, subclinical disorders, or systemic kidney insults[4,11,12]. Elevated baseline OPN may reflect subclinical renal tubular injury that is not detected by conventional measures, such as serum creatinine[11,12]. Alternatively, it may indicate a heightened systemic inflammatory state, which could predispose patients to exaggerated renal inflammatory responses following contrast administration[20,21]. Given the close relationship between atherosclerosis, cardiovascular inflammation, and OPN expression, higher pre-procedural OPN levels may also represent a shared inflammatory milieu linking cardiovascular disease and renal susceptibility[20-22].

Mechanism of OPN in AKI

From a mechanistic perspective OPN is known to play an active role in renal inflammation and injury. Experimental studies have demonstrated that OPN regulates macrophage adhesion and chemotaxis, facilitating immune cell infiltration into injured renal tissue[5,8,9,11]. In addition, OPN participates in proinflammatory signaling pathways involving interleukin-1β and tumor necrosis factor-α and can activate nuclear factor kappa B, thereby amplifying inflammatory cascades within the kidney[8,12,20]. Through these mechanisms OPN may increase the susceptibility of renal tubular epithelial cells to injury and exacerbate contrast-induced renal damage[11,12,21]. In the current study these mechanisms might be considered the renal biological activities and responses to the contrast that translate clinically into CA-AKI.

Study advantages

Based on the current results, the enhanced predictive performance of the combined OPN and Mehran score suggests that while clinical risk factors capture baseline susceptibility biomarkers such as OPN provide a real-time measure of renal vulnerability, improving the precision of risk assessment. To our knowledge the current study was the first to report on the role of the combined OPN and Mehran risk score in predicting CA-AKI.

Additionally, the current study is the second report to investigate the value of OPN in the early prediction of CA-AKI in patients undergoing PCI. The first study on this topic was conducted by Mohebi et al[26], who found that patients with CA-AKI had higher levels of OPN. Furthermore, the current study specified the timing at which OPN was measured. This schedule may be useful for accurately assessing how OPN can predict early CA-AKI.

Study limitations

The current study had several limitations. The sample size of patients with CA-AKI was only 20 cases, increasing the risk of overfitting in the statistical model. Additionally, the single-center design limited external promotion of the current results. Furthermore, no long-term follow-up of those patients was conducted to assess the frequency of transition to chronic kidney disease in patients who developed CA-AKI. Lastly, failure to measure the urinary levels of OPN leads to an inability to compare differences between blood and urine levels.

CONCLUSION

The rate of CA-AKI was around 13% for patients who underwent PCI. Elevated pre-PCI and post-PCI serum OPN, higher contrast volume, and elevated Mehran score were independent predictors of CA-AKI. Pre-procedural OPN and Mehran score, individually and in combination, demonstrated high diagnostic accuracy, suggesting their value in early risk stratification. Routine measurement of serum OPN before PCI could serve as an early biomarker to identify patients at risk for CA-AKI. The existing shortcomings of the literature underscore the need for larger-scale, multicenter studies with rigorous validation processes.