Predictive factors of contrast-induced nephropathy in patients undergoing primary coronary angioplasty




Summary


Background


Contrast-induced nephropathy (CIN) severely impacts patient morbidity and mortality, especially in patients with ST-segment elevation myocardial infarction treated by primary coronary angioplasty, whose renal function is often unknown at the time of contrast exposure.


Aim


We sought the incidence and factors predictive of CIN in patients treated by primary coronary angioplasty in our hospital; we also questioned the relevance of Mehran’s risk score in this population.


Methods


We considered all patients admitted for primary coronary angioplasty between January 2010 and December 2011, and included 322 patients with complete data on renal function. CIN was defined as a relative (≥ 25%) or absolute (≥ 44 μmol/L) increase in serum creatinine following contrast medium administration. We compared patients with or without CIN, to identify predictive factors, and investigated the effectiveness of Mehran’s score using a receiver operating characteristic (ROC) curve, Youden’s index and a likelihood ratio test.


Results


The incidence of CIN was 9.1%. A multivariable analysis identified two independent risk factors for CIN: impaired glomerular filtration rate and cardiogenic shock at admission ( P < 0.05). An elevated Mehran’s score was associated with increased incidence of CIN, but statistical analysis revealed this score to have poor sensitivity, especially in high-risk patients. Youden’s index was very low and the area under the ROC curve was 0.59 in our population.


Conclusion


Renal failure and cardiogenic shock at admission were independent predictors of CIN in our acute myocardial infarction population. Mehran’s score added little to the discrimination of patients undergoing primary coronary angioplasty, particularly high-risk individuals.


Résumé


Contexte


La néphropathie de contraste impacte le pronostic des patients admis pour infarctus du myocarde avec sus-décalage du segment ST traités par angioplastie primaire, pour qui la fonction rénale est généralement inconnue lors de la prise en charge.


Objectif


Nous nous sommes intéressés à l’incidence de la néphropathie de contraste chez les patients admis dans notre centre pour angioplastie primaire et avons cherché à déterminer l’applicabilité du score de risque de Mehran dans ce contexte.


Méthodes


Nous avons inclus 322 patients entre janvier 2010 et décembre 2011. La néphropathie de contraste était définie comme une élévation relative (≥ 25 %) ou absolue (≥ 44 μmol/L) de la créatininémie au décours de l’injection de produit de contraste. Nous avons évalué la pertinence du score de Mehran en comparant patients avec ou sans néphropathie de contraste en utilisant des rapports de vraisemblance, index de Youden ou courbe ROC.


Résultats


L’incidence de la néphropathie de contraste était 9,1 %. En analyse multivariée, seuls l’insuffisance rénale préexistante et le choc cardiogénique à l’admission étaient prédictifs de néphropathie de contraste ( p < 0,05). Un score de Mehran élevé s’accompagnait d’une augmentation d’incidence de néphropathie de contraste mais la sensibilité de ce test restait faible, en faisant un outil peu utile comme en témoignaient les index de Youden bas et l’aire sous la courbe ROC à 0,59.


Conclusion


Insuffisance rénale et choc cardiogénique apparaissent comme les seuls prédicteurs de néphropathie de contraste chez les patients admis pour infarctus du myocarde. L’utilité du score de Mehran n’apparaît pas démontrée dans cette population.


Background


Contrast-induced nephropathy (CIN) refers to potentially reversible acute renal failure following iodinated contrast medium exposure during angiographical procedures or computed tomography . CIN generally occurs within 48 hours of contrast exposure, the increase in serum creatinine peaking 5–7 days later and usually recovering within 7–10 days , with the majority of patients returning to their baseline values. Clinical and metabolic disorders requiring renal replacement therapy occur in approximately 3% of patients . The risk of CIN is even higher in patients referred for primary coronary angioplasty in the context of acute coronary syndromes . CIN is responsible for an increased mortality rate of 14% and, for most patients, correlates with increases in hospital stays and the risk of cardiovascular complications .


Significant progress regarding contrast media composition, notably the decrease in osmolarity and the constant use of intravenous hydration in high-risk patients, have resulted in a reduction in the incidence of CIN from 15% to nearly 7% over a decade . However, because of the increasing number of procedures with iodinated contrast media exposure and population aging, resulting in an increased prevalence of chronic kidney failure, CIN and its impact on morbidity and mortality remains a growing concern.


While it seems that intra-arterial administration of contrast medium is associated with a higher risk of CIN than intravenous infusion , primary coronary angioplasty appears to be a particularly high-risk procedure, as it affects a population at greater risk of CIN (i.e. older patients with co-morbidities, such as diabetes, heart failure and chronic renal failure) . Primary coronary angioplasty has been shown to be effective in reducing morbimortality in patients admitted for acute myocardial infarction, and is the corner stone of first-line therapy in these patients. The main pitfall is that renal function is often unknown at the time of contrast exposure because primary coronary angioplasty has to be performed without delay, leaving no time for renal function assessment. Moreover, the short delay between patient admission and primary coronary angioplasty significantly limits the use of pedigree renal protection measures, such as intravenous hydration (at least prior to the procedure).


Several risk scores have been developed in accordance with the main risk factors identified for CIN, but none has been adequately validated in the literature ; thus they are currently not recommended for daily practice by the CIN Consensus Working Panel . Risk scores could, however, be of significant help in assessing the risk of CIN in populations where up-to-date data regarding renal function are missing (e.g. patients undergoing primary coronary angioplasty).


The objective of this study was to determine the incidence of CIN in patients treated by primary coronary angioplasty for ST-segment elevation myocardial infarction (STEMI) in Tours University Hospital. We also aimed to assess factors predictive of CIN in this population and the efficacy of the reference predictive test (Mehran’s score).




Methods


Study population


We performed a retrospective single-centre study. All patients undergoing primary coronary angioplasty for STEMI between January 2010 and December 2011 in our University Hospital (Tours, France) were considered for inclusion.


STEMI was defined according to the European Society of Cardiology criteria, as: any chest pain lasting > 10 minutes associated with a significant increase in cardiac biomarkers and/or associated with new or presumed new ST-segment elevation of 0.2 mV in at least two contiguous leads or with the onset of a left bundle branch block . Patients’ aged ≥ 18 years who had had primary coronary angioplasty (successful or not) were eligible. Patients were excluded if they had been exposed to contrast injection within 7 days before coronary angioplasty or were on chronic renal replacement therapy.


Study protocol


Baseline serum creatinine concentration was measured from a blood sample obtained immediately after hospital admission or at the beginning of primary coronary angioplasty. The result was usually unavailable at the time of primary coronary angioplasty. Measurements were usually repeated at 24, 48 and 72 hours during the patient’s stay in the intensive coronary care unit. All blood samples were processed by the same laboratory in our hospital (AU2700Plus™ chemistry analyser, Beckman Coulter, Brea, CA, USA; and AU640™ immunochemistry analyser, Olympus, Center Valley, PA, USA). Creatinine clearance was calculated using the modified modification of diet in renal disease (MDRD) equation.


According to local custom, most patients received intravenous infusion of a 5% glucose solution from initial management by emergency crew to arrival in the catheterization laboratory. No preventive measures for CIN were recommended. After coronary angioplasty, infusion of a 5% glucose solution followed at the usual rate of 1 mL/kg/h, reduced to 0.5 mL/kg/h in patients with an impaired left ventricular ejection fraction (< 40%), overt heart failure or cardiogenic shock.


Coronary revascularization


Following our local procedure, primary coronary angioplasty was performed using either radial or femoral access (at the discretion of the operator), with size 6F guide catheters. Patients received a prehospital injection of acetylsalicylic acid 250 mg in addition to clopidogrel 600 mg or prasugrel 60 mg when eligible, and an intravenous bolus of unfractionated heparin (4000–6000 IU, adapted to weight). All patients received a monomer non-ionic low-osmolar contrast agent (iohexol, OMNIPAQUE™, GE Healthcare Pharmaceuticals, Chalfont St. Giles, UK). After identification, the culprit lesions were treated by direct coronary stenting or by balloon predilatation followed by stenting, at the discretion of the operator. The volume of contrast agent, the angioplasty technique and the use of pharmaceutical or mechanical haemodynamic support were in accordance with the European Society of Cardiology guidelines .


Cardiogenic shock was defined as acute circulatory failure of cardiac origin with a systolic arterial pressure < 80 mmHg, refractory to intravenous infusion of 500 mL of saline over 30 minutes and resulting in at least two additional organ failures.


According to our emergency protocol, renal support (haemodialysis or haemofiltration) was proposed in cases of anuria lasting > 24 hours, independent of the patient’s haemodynamic status.


Endpoints


The main endpoint was the occurrence of CIN, defined as a relative (≥ 25%) or absolute (≥ 0.5 mg/dL; 44 μmol/L) increase in serum creatinine from baseline within 3 days after primary coronary angioplasty. Kidney disease and chronic renal failure were defined according to the recommendations of the European Society of Nephrology, as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m 2 , estimated with the modified MDRD formula .


Concomitantly, the risk of CIN was assessed by application of Mehran’s score , based on the following eight variables: age (> or < 75 years); hypotension; congestive heart failure; need for haemodynamic support with intra-aortic balloon pump (IABP); baseline serum creatinine; diabetes; anaemia; and volume of contrast agent. Mehran’s score categorized our population into four different groups according to their estimated risk of CIN: a low-risk group (score < 5); a medium-risk group (5 < score < 10); a high-risk group (10 < score < 15); and a very high-risk group (score > 15).


Statistical analysis


Continuous data were expressed as mean values ± standard deviations. Categorical data were reported as percentages and absolute values. Comparisons between groups were made using the Chi 2 test for categorical variables and Student’s t -test for continuous variables. A continuous regression model was used to identify variables independently associated with the occurrence of specified adverse events during follow-up. Potential confounders were included in the statistical model to fit. The results are expressed as relative risks with 95% confidence intervals (CIs). A P value < 0.05 was considered statistically significant. Statistical analyses were performed with JMP 9.1 software (JMP ® , SAS ® and all others, SAS Institute Inc., Cary, NC, USA). We tested the sensitivity, specificity, positive predictive value and negative predictive value of Mehran’s score for each patient risk group. We used several indicators to assess the informative value of the score, including positive likelihood, negative likelihood, Youden’s index and ROC curve. Youden’s index, also known as Youden’s J statistic, is a helpful validated tool to assess the performance of a diagnostic test ; it is easily calculated according to the formula J = sensitivity + specificity − 1.




Results


Between January 2010 and December 2011, 427 patients were admitted for STEMI and underwent primary coronary angioplasty. Of these, 322 patients with complete data on renal function at baseline and during the 3-day follow-up period were included ( Fig. 1 ). Patient characteristics are presented in Tables 1–3 .




Figure 1


Study design and flowchart. CIN: contrast-induced nephropathy; GFR: glomerular filtration rate.


Table 1

Demographic characteristics of the study population and treatment at admission.




























































































































































Global population
( n = 322; 100%)
CIN (+)
( n = 30; 9.3%)
CIN (−)
( n = 292; 90.7%)
P
Age (years) 63.8 ± 14.4 63.7 ± 14.4 63.8 ± 14.4 0.208
Age > 75 years 77 (23.9) 12 (40.0) 65 (22.3) 0.042
Women 76 (23.6) 8 (26.7) 68 (23.3) 0.7
BMI (g/m 2 ) 27.0 ± 4.9 27.8 ± 4.4 26.9 ± 4.7 0.524
Diabetes 60 (18.6) 8 (26.7) 52 (17.8) 0.234
Type I diabetes 2 (0.3) 0 (0) 2 (0.7) 0.559
Type II diabetes 58 (18.0) 8 (26.7) 50 (17.1) 0.197
Arterial hypertension 163 (50.6) 20 (66.7) 143 (49.0) 0.155
Dyslipidaemia 119 (36.9) 11 (36.7) 108 (37.0) 0.978
Current smoker 131 (40.7) 11 (36.7) 120 (41.1) 0.673
Familial IHD history 38 (11.8) 3 (10.0) 35 (12.0) 0.731
Personal IHD history 38 (11.8) 6 (20.0) 32 (11.0) 0.161
Personal PAD history 21 (6.5) 2 (6.7) 19 (6.6) 0.951
Diuretics 55 (17.1) 7 (23.4) 48 (16.4) 0.349
Thiazide diuretics 29 (9.0) 5 (16.7) 24 (8.2) 0.283
ARBs 53 (16.5) 5 (16.7) 48 (16.4) 0.975
ACE inhibitors 29 (9.0) 5 (16.7) 24 (8.2) 0.391
Statins 82 (25.5) 8 (26.7) 74 (25.3) 0.889
Antiplatelet therapy 60 (18.6) 9 (30.0) 51 (17.5) 0.115

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Jul 12, 2017 | Posted by in CARDIOLOGY | Comments Off on Predictive factors of contrast-induced nephropathy in patients undergoing primary coronary angioplasty

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