Article

PDF
Access to the PDF text
Advertising


Free Article !

Archives of cardiovascular diseases
Volume 102, n° 11
pages 761-767 (novembre 2009)
Doi : 10.1016/j.acvd.2009.07.001
Received : 4 June 2009 ;  accepted : 23 July 2009
Preventing acute decrease in renal function induced by coronary angiography (PRECORD): a prospective randomized trial
Prévention de la néphropathie de contraste au cours de la coronarographie (étude PRECORD)
 

Denis Angoulvant a, Michel Cucherat b, Gilles Rioufol a, Gérard Finet a, Jacques Beaune a, Didier Revel a, Maurice Laville c, Michel Ovize a, Xavier André-Fouët a,
a Service de cardiologie D, hôpital cardiovasculaire et pneumologique Louis-Pradel, groupement hospitalier Est, université Claude-Bernard Lyon-1, 28, avenue Doyen-Lepine, 69677 Bron cedex, France 
b EA643, Department of Biostatistics, CHU de Lyon, université Claude-Bernard Lyon-1, 69376 Lyon cedex 08, France 
c Department of Nephrology, hôpital Édouard-Herriot, université Claude-Bernard Lyon-1, 69003 Lyon, France 

Corresponding author. Fax: +33 4 72 35 73 76.
Summary
Background

Infusion of saline attenuates the decrease in renal function induced by radiographic contrast agents among patients with chronic renal insufficiency.

Aim

The Preventing Renal alteration in Coronary Disease (PRECORD) trial was a randomized trial to assess the effect on renal function of saline infusion during and after coronary angiography in 201 patients without severe chronic renal insufficiency (serum creatinine<140μmol/L).

Methods

All patients received standard oral hydration: 2000mL of tap water within the 24hours after coronary angiography. Patients were randomized before the procedure to intravenous hydration (1000mL of 0.9% saline infusion) or no additional hydration. The infusion was started in the catheterization laboratory and continued for 24hours. The primary endpoint was the change in calculated creatinine clearance between baseline and 24hours after coronary angiography. The same ionic low osmolar radiographic contrast agent (ioxaglate) was used in all patients.

Results

Both groups had similar baseline characteristics, including age, serum creatinine, volume of contrast and proportion of patients undergoing ad hoc coronary angioplasty. The overall decrease in serum creatinine clearance 24hours after the procedure was –3.44 (0.68)mL/min. The change in serum creatinine clearance 24hours after the procedure was –2.81 (1.07)mL/min in the infusion group vs –4.09 (0.91)mL/min in the control group (p =0.38).

Conclusion

Renal function is altered only slightly 24hours after coronary angiography with standard oral hydration alone and is not affected by saline infusion started at the beginning of coronary angiography, even in patients with mild-to-moderate renal dysfunction.

The full text of this article is available in PDF format.
Résumé
Prérequis

La perfusion de sérum salé prévient la dégradation de la fonction rénale après injection de produit de contraste chez les insuffisants rénaux chroniques.

Objectif

L’étude Preventing Renal alteration in Coronary Disease (PRECORD) est un essai thérapeutique randomisé évaluant l’effet protecteur de la perfusion de sérum salé au cours d’une coronarographie chez 201 patients non insuffisants rénaux sévères (créatininémie<140μmol/L).

Méthodes

Tous les patients recevaient une hydratation orale de 2000mL d’eau du robinet dans les 24heures suivant la coronarographie. Les patients étaient randomisés avant l’examen en deux groupes : un groupe recevant une hydratation supplémentaire par sérum salé 0,9 % intraveineux 1000mL débuté en salle de cathétérisme et poursuivi pendant 24 heures, et un groupe témoin sans hydratation supplémentaire. Le critère majeur était la diminution de la clairance de la créatininémie calculée à 24heures. Pendant la coronarographie, tous les patients recevaient le même agent de contraste ionique à osmolarité basse (ioxaglate).

Résultats

Les deux groupes étaient comparables à l’inclusion en ce qui concerne l’age, la créatininémie, la quantité de produit de contraste et le nombre d’angioplastie. La diminution moyenne de la clairance de la créatininémie observée à 24heures était de –3,44 (0,68)mL/min. Dans le groupe recevant la perfusion de sérum salé elle était de –2,81 (1,07)mL/min et dans le groupe témoin de –4,09 (0,91)mL/min (p =0,38).

Conclusion

La fonction rénale n’est que modérément altérée après une coronarographie chez les patients recevant une hydratation préventive per os. L’ajout d’une hydratation intraveineuse en début de coronarographie n’entraîne pas de bénéfice significatif chez des patients n’ayant pas d’insuffisance rénale sévère.

The full text of this article is available in PDF format.

Keywords : Acute renal insufficiency, Contrast agent, Coronary angiography, Prevention, Randomized controlled trial

Mots clés : Produit de contraste, Insuffisance rénale aiguë, Prévention, Coronarographie, Essai thérapeutique randomisé

Abbreviations : CI, CIN, PTCA, SEM


Background

Contrast-induced acute nephropathy (CIN) is an important complication associated with the use of iodinated contrast media and accounts for a significant number of cases of hospital-acquired acute renal insufficiency [1]. CIN is typically defined as an increase in serum creatinine occurring within the first 24hours after contrast exposure and peaking up to five days later [2]. CIN after percutaneous coronary intervention has been shown to increase the risk of death significantly, necessitating the evaluation of preventive strategies [3].

Important risk factors are preexistent renal insufficiency (particularly when associated with diabetes), contrast volume and dehydration [4, 5, 6]. In an unselected population, the rate of acute decrease in renal function – defined as a 25% increase in serum creatinine concentration – was 14.5% after percutaneous coronary intervention [7]. In patients without preexistent chronic renal insufficiency, an acute decrease in renal function induced by the administration of radiographic contrast agents has been reported in up to 10% of patients [5, 8, 9, 10].

Several prophylactic measures have been evaluated in patients at high risk [11, 12, 13, 14, 15, 16, 17]. Previous studies suggest that volume expansion using isotonic crystalloid, saline or bicarbonate solution is an effective means of preventing a further acute decrease in renal function induced by radiographic contrast agents in patients with chronic renal insufficiency [18, 19, 20].

No prospective randomized study has evaluated intravenous saline hydration in patients without preexistent chronic renal insufficiency. The Preventing Renal alteration in Coronary Disease (PRECORD) study was a prospective, randomized, controlled, open-label study that investigated the benefit on renal function of saline infusion during and after elective coronary angiography in patients without preexistent chronic renal insufficiency.

Methods
Patients

All consecutive patients between the ages of 18 and 80 years scheduled for elective coronary angiography, with or without percutaneous transluminal coronary angioplasty (PTCA), who had a baseline serum creatinine concentration below 140μmol/L (1.58mg/dL) between September 2000 and March 2001 were eligible for the study. Exclusion criteria included New York Heart Association class IV congestive heart failure, pregnancy, significant valvular heart disease, nonischaemic dilated cardiomyopathy, active cancer or any life-threatening disease. The study protocol was approved by the local ethics committee and all patients gave written informed consent.

Study protocol

According to our hospital guidelines, all patients received oral hydration with 2000mL of tap water in the 24hours after coronary angiography.

Patients were assigned treatment randomly upon arrival in the catheterization laboratory by means of computer-generated randomization. The randomization was stratified according to sex and baseline creatinine level by a minimization algorithm.

The infusion group received 1000mL of 0.9% saline infusion, which was started at the beginning of the procedure and continued for the next 24hours. The control group received no additional hydration.

Abdominal aortography was performed systematically after left ventriculography in the 20° left oblique anterior projection, to screen for the presence of renal artery stenosis. By convention, an angiographically significant lesion was defined as a greater than or equal to 50% luminal diameter narrowing of a major renal artery [21].

An ionic low osmolar radiographic contrast agent (sodium and meglumine ioxaglate; Hexabrix® 320mg I/mL, Laboratoires Guerbet, Roissy CdG, France) was used for all patients.

The primary endpoint was the change in serum creatinine clearance between baseline and 24hours after coronary angiography.

Serum creatinine was measured in our hospital laboratory 12 to 24hours before, and 24hours after, coronary angiography. After discharge, one additional determination of serum creatinine was performed in an external laboratory, three days after coronary angiography. Creatinine clearance was calculated with the Cockcroft and Gault formula from serum creatinine concentration, weight, age and sex [22].

Statistical analysis

Based on a between-subject standard deviation of 24-hour percentage change in creatinine clearance of 15%, a trial of 168 patients would have a power of more than 90% to detect, as significant at the 5% level, an average difference of 7.5% between the two treatments. We aimed to recruit 200 patients to allow for withdrawals and noncompliance.

All analyses were done according to a prespecified statistical analysis plan by intention to treat. The analysis compared creatinine clearance value at 24hours between the two treatments, with adjustment for the baseline values by analysis of covariance. Analyses were performed on R software. Statistical analyses ignoring these baseline results produced similar results. All p -values were two-tailed; 95% confidence intervals (CIs) were calculated for differences within and between treatment groups. All results are reported as means (SEM).

Results

Between September 2000 and March 2001, 201 patients were assigned randomly to the infusion group (100 patients) or the control group (101 patients) in our department; their baseline characteristics are shown in Table 1. The two groups were similar with respect to age, baseline creatinine clearance, body mass index and concomitant medication. Cardiac catheterization, angiographic and procedural details before any oral or intravenous hydration are shown in Table 2.

Serum creatinine 24hours after the procedure was measured in 97 patients from the infusion group and 96 patients from the control group. Serum creatinine three days after the procedure was measured in 74 patients from the infusion group and 85 patients from the control group. In the infusion group, mean serum creatinine clearance varied from 85.7 (2.58)mL/min at baseline to 82.5 (2.62)mL/min 24hours after coronary angiography. Corresponding values in the control group were 85.8 (2.65)mL/min and 82 (2.72)mL/min. Serum creatinine clearance values for both groups are presented in Figure 1.



Figure 1


Figure 1. 

Serum creatinine clearance at baseline, 24hours and three days after angiography. Error bars are the standard error of the mean.

Zoom

The mean overall decrease in serum creatinine clearance 24hours after the procedure was –3.44 (0.68)mL/min. Changes in serum creatinine clearance 24hours and three days after coronary angiography in both groups are presented in Table 3.

The mean change in serum creatinine clearance 24hours after angiography in patients receiving antihypertensive therapy was –1.98 (1.13)mL/min in the infusion group (n =44) vs –4.12 (1.58)mL/min in the control group (n =37). The mean change in serum creatinine clearance 24hours after angiography in patients receiving antidiabetic therapy was –3.31 (3.2)mL/min in the infusion group (n =16) vs 0.88 (3.88)mL/min in the control group (n =12).

A comparison of serum creatinine clearance before and 24hours after angiography in the different quartiles is shown in Table 4. Twenty-four hours after the procedure, an increase in serum creatinine of more than 25% occurred in six patients (6%) in the infusion group and four patients (3.9%) in the control group. Three days after the procedure, an increase in serum creatinine of more than 25% occurred in five patients (5%) in the infusion group and seven patients (6.9%) in the control group.

Angiographically significant renal artery stenosis was found in 13 patients (nine in the infusion group and four in the control group); their mean baseline creatinine clearance of 79.05 (7.04)mL/min did not differ significantly from that of the overall population (85.76 [1.84]mL/min; p =0.38). No patient required dialysis or died within 30 days after the procedure.

Discussion

Changes in serum creatinine clearance 24hours after coronary angiography were moderate with standard oral hydration in patients without severe renal dysfunction. We found no benefit of additional intravenous hydration started at the beginning of coronary angiography in our population.

The PRECORD study is the first prospective, randomized trial evaluating intravenous hydration in patients scheduled for elective coronary angiography without preexistent chronic renal insufficiency. It is also the first study using standardized oral hydration for all patients. As expected from studies reported previously, the incidence of acute decrease in renal function was low in our population [23]. In previous studies an acute decline in renal function was generally defined as a rise in serum creatinine of more than 25% within three days of administration of radiographic contrast agents. We used calculated creatinine clearance from the formula of Cockcroft and Gault, which is a more accurate means of estimating glomerular filtration rate than using serum creatinine concentration alone [4, 24]. On inclusion, all patients had serum creatinine concentrations below 140μmol/L (1.58mg/dL), which was considered to reflect normal renal function. The second quartile had a serum creatinine clearance below 90mL/min, which indicates mild renal dysfunction, and the first quartile had a serum creatinine clearance below 60mL/min, which indicates moderate renal insufficiency. In these quartiles, the change in serum creatinine clearance 24hours after coronary angiography did not differ significantly between groups. In accordance with previous studies we found a 5% incidence of significant acute decline in renal function (defined as a rise in serum creatinine greater than 25% above the baseline) at 24hours and a 6% incidence at three days, with no difference between infusion and control groups.

Our study compared oral hydration with a combination of oral and intravenous hydration. Previous studies used 0.45% saline infusion at a rate of 1mL per kilogram of body weight per hour, beginning 12hours before angiography. In a randomized trial, hydration using 0.9% saline infusion has been shown to be more effective than 0.45% saline infusion in the prevention of acute decline in renal function after coronary angiography, even without precatheterization hydration [23]. The combination of oral and intravenous hydration has been shown to be effective in preventing acute changes in renal function in patients with mild-to-moderate renal dysfunction in a prospective, randomized trial [25]. Adequate intravenous volume expansion with isotonic crystalloid (1–1.5mL/kg per hour) for 3–12hours before the administration of iodinated contrast media and continued for 6–24hours afterwards is a well established and recommended method for reducing the risk of CIN in patients with chronic renal failure [26]. In the present study, saline infusion was started only at the beginning of the procedure, and not several hours before, which decreases the potential protective effect of intravenous hydration on CIN. Therefore we cannot exclude a benefit of intravenous hydration started 3–12hours before the procedure in our population. The volume of saline infusion and water intake was not adjusted to body weight or clinical conditions. All patients received 2000mL of tap water after coronary angiography and the infusion group received 1000mL of 0.9% saline infusion started at the beginning of coronary angiography. We did not observe any hydration-induced pulmonary oedema even in patients with impaired left ventricular function.

In our population, baseline-calculated serum creatinine clearance was at the 75th percentile according to population age- and sex-based standards [27]. We measured serum creatinine 24hours and three days after coronary angiography to avoid underestimating the occurrence of radiocontrast-induced decrease in renal function [28]. Most patients were discharged within 48hours after coronary angiography. The change in serum creatinine clearance 24hours after coronary angiography was our major endpoint because serum creatinine was measured in the same hospital laboratory as baseline serum creatinine. Serum creatinine clearance three days after coronary angiography would have been more sensitive but it was measured in various external laboratories, leading to greater measurement variability. Absolute changes in creatinine clearance three days after coronary angiography were similar in both groups.

Our study excluded patients with preexistent chronic renal insufficiency diagnosed on the basis of baseline serum creatinine and/or past medical history. We screened for the presence of renal artery stenosis to evaluate the incidence of potential ischaemic renal disease and its influence on renal function after coronary angiography. We found a 6.5% incidence of angiographically significant renal artery stenosis in our population, which is in keeping with previously reported studies [21, 29]; baseline creatinine clearance and change in creatinine clearance 24hours after coronary angiography did not differ significantly between these patients and the rest of our population.

All patients received the same low osmolar ionic radiocontrast media that is preferred over nonionic contrast media in coronary angiography [30]. The volume of radiocontrast media and the iodine dose administered were moderate and similar to those in a recent study in comparable patient cohorts [23]. Previous studies have shown that the use of ionic radiographic contrast agent is not associated with a higher incidence of acute decrease in renal function compared with nonionic contrast agent [31].

Renal protection in coronary patients is a major concern because altered renal function in essential hypertension, advanced heart failure and after a myocardial infarction is associated with higher cardiovascular morbidity and mortality [32, 33, 34]. The expanding use of diagnostic and therapeutic coronary angiography makes it important to establish recommendations for nephroprotection, even in patients without preexistent chronic renal insufficiency. Acute radiocontrast nephropathy is not the only potential cause of renal impairment after coronary angiography. Cholesterol embolization induced by the introduction of catheters is probably underreported, but generally presents with a progressive decline in renal function a few weeks rather than a few days after the procedure [35]. There is no reason to expect that oral or intravenous hydration would prevent this late complication of coronary angiography.

Conclusion

We found no evidence of a benefit of intravenous hydration with 0.9% saline started at the beginning of coronary angiography over standard oral hydration with tap water after coronary angiography on renal function in patients with normal or mild-to-moderate renal dysfunction.

Conflicts of interest

None.


Acknowledgements

Financial support was provided by the Division of Research, hospices civils de Lyon, Lyon, France, and Guerbet Laboratories, Roissy CdG, France.

References

Hou S.H., Bushinsky D.A., Wish J.B., and al. Hospital-acquired renal insufficiency: a prospective study Am J Med 1983 ;  74 : 243-248 [cross-ref]
McCullough P.A. Contrast-induced acute kidney injury J Am Coll Cardiol 2008 ;  51 : 1419-1428 [cross-ref]
Rihal C.S., Textor S.C., Grill D.E., and al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention Circulation 2002 ;  105 : 2259-2264 [cross-ref]
Morcos S.K. Contrast media-induced nephrotoxicity – questions and answers Br J Radiol 1998 ;  71 : 357-365
Rich M.W., Crecelius C.A. Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A prospective study Arch Intern Med 1990 ;  150 : 1237-1242
Weisberg L.S., Kurnik P.B., Kurnik B.R. Risk of radiocontrast nephropathy in patients with and without diabetes mellitus Kidney Int 1994 ;  45 : 259-265 [cross-ref]
McCullough P.A., Wolyn R., Rocher L.L., and al. Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality Am J Med 1997 ;  103 : 368-375 [cross-ref]
Martin-Paredero V., Dixon S.M., Baker J.D., and al. Risk of renal failure after major angiography Arch Surg 1983 ;  118 : 1417-1420
Mason R.A., Arbeit L.A., Giron F. Renal dysfunction after arteriography JAMA 1985 ;  253 : 1001-1004
Parfrey P.S., Griffiths S.M., Barrett B.J., and al. Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study N Engl J Med 1989 ;  320 : 143-149
Erley C.M., Duda S.H., Schlepckow S., and al. Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application Kidney Int 1994 ;  45 : 1425-1431 [cross-ref]
Kapoor A., Sinha N., Sharma R.K., and al. Use of dopamine in prevention of contrast-induced acute renal failure – a randomised study Int J Cardiol 1996 ;  53 : 233-236 [cross-ref]
Kini A.S., Mitre C.A., Kim M., and al. A protocol for prevention of radiographic contrast nephropathy during percutaneous coronary intervention: effect of selective dopamine receptor agonist fenoldopam Catheter Cardiovasc Interv 2002 ;  55 : 169-173 [cross-ref]
Kurnik B.R., Allgren R.L., Genter F.C., and al. Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy Am J Kidney Dis 1998 ;  31 : 674-680 [cross-ref]
Stevens M.A., McCullough P.A., Tobin K.J., and al. A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the PRINCE. Study. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation J Am Coll Cardiol 1999 ;  33 : 403-411 [cross-ref]
Tepel M., van der Giet M., Schwarzfeld C., and al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine N Engl J Med 2000 ;  343 : 180-184 [cross-ref]
Vogt B., Ferrari P., Schonholzer C., and al. Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful Am J Med 2001 ;  111 : 692-698 [cross-ref]
Eisenberg R.L., Bank W.O., Hedgock M.W. Renal failure after major angiography can be avoided with hydration AJR Am J Roentgenol 1981 ;  136 : 859-861
Merten G.J., Burgess W.P., Gray L.V., and al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial JAMA 2004 ;  291 : 2328-2334 [cross-ref]
Solomon R., Werner C., Mann D., and al. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents N Engl J Med 1994 ;  331 : 1416-1420 [cross-ref]
Harding M.B., Smith L.R., Himmelstein S.I., and al. Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization J Am Soc Nephrol 1992 ;  2 : 1608-1616
Cockcroft D.W., Gault M.H. Prediction of creatinine clearance from serum creatinine Nephron 1976 ;  16 : 31-41 [cross-ref]
Mueller C., Buerkle G., Buettner H.J., and al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty Arch Intern Med 2002 ;  162 : 329-336 [cross-ref]
K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266.
Taylor A.J., Hotchkiss D., Morse R.W., and al. PREPARED: Preparation for Angiography in Renal Dysfunction: a randomized trial of inpatient vs outpatient hydration protocols for cardiac catheterization in mild-to-moderate renal dysfunction Chest 1998 ;  114 : 1570-1574 [cross-ref]
Stacul F., Adam A., Becker C.R., and al. Strategies to reduce the risk of contrast-induced nephropathy Am J Cardiol 2006 ;  98 : 59K-77K [cross-ref]
Elseviers M.M., Verpooten G.A., De Broe M.E., and al. Interpretation of creatinine clearance Lancet 1987 ;  1 : 457 [cross-ref]
Rudnick M.R., Berns J.S., Cohen R.M., and al. Nephrotoxic risks of renal angiography: contrast media-associated nephrotoxicity and atheroembolism – a critical review Am J Kidney Dis 1994 ;  24 : 713-727
Crowley J.J., Santos R.M., Peter R.H., and al. Progression of renal artery stenosis in patients undergoing cardiac catheterization Am Heart J 1998 ;  136 : 913-918 [cross-ref]
Grines C.L., Schreiber T.L., Savas V., and al. A randomized trial of low osmolar ionic versus nonionic contrast media in patients with myocardial infarction or unstable angina undergoing percutaneous transluminal coronary angioplasty J Am Coll Cardiol 1996 ;  27 : 1381-1386 [cross-ref]
Schwab S.J., Hlatky M.A., Pieper K.S., and al. Contrast nephrotoxicity: a randomized controlled trial of a nonionic and an ionic radiographic contrast agent N Engl J Med 1989 ;  320 : 149-153
Aronow W.S., Ahn C., Mercando A.D., and al. Prevalence of coronary artery disease, complex ventricular arrhythmias, and silent myocardial ischemia and incidence of new coronary events in older persons with chronic renal insufficiency and with normal renal function Am J Cardiol 2000 ;  86 : 1142-1143A9.  [cross-ref]
Gruberg L., Mintz G.S., Mehran R., and al. The prognostic implications of further renal function deterioration within 48h of interventional coronary procedures in patients with preexistent chronic renal insufficiency J Am Coll Cardiol 2000 ;  36 : 1542-1548 [cross-ref]
Ruilope L.M., van Veldhuisen D.J., Ritz E., and al. Renal function: the Cinderella of cardiovascular risk profile J Am Coll Cardiol 2001 ;  38 : 1782-1787 [cross-ref]
Om A., Ellahham S., DiSciascio G. Cholesterol embolism: an underdiagnosed clinical entity Am Heart J 1992 ;  124 : 1321-1326 [cross-ref]



© 2009  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Close
Article Outline