Author + information
- Christopher S.R. Baker, PhD, MRCP* (, )
- Atholl Johnston, PhD, MRCPath*,
- Laurence R.I. Baker, MD, FRCP* and
- Charles J. Knight, MD, MRCP*
DiDomenico and Eyrich question the definition of radiocontrast-induced nephropathy (RCIN) and whether contrast nephropathy occurred in the RAPPID study. The definition of RCIN employed (a rise in serum creatinine ≥25%) is a widely accepted one and has been used extensively (1–4). Furthermore, the clinical importance of this definition has been demonstrated by the attendant increase in in-hospital mortality when coronary intervention is associated with this degree of renal impairment (1). The other commonly used definition is a 0.5-mg/dl increase in serum creatinine postcontrast exposure (5–9). Using this definition, the incidence of RCIN in both control and n-acetylcysteine (NAC)-treated groups of our study remains unchanged (Fig. 1).
Other suggested end points are unlikely to provide a more appropriate reflection of deteriorating renal function. The incidence of RCIN requiring renal replacement therapy, although of considerable importance, is low following intra-arterial contrast (7.7 cases per 1,000) and thus would require the study of many thousands of patients (1). Change in urine output would be a difficult end point to analyze, being dependent on standardization of fluid intake. In addition, RCIN is frequently nonoliguric (10). Change in creatinine clearance is perhaps the most accurate measure of change in renal function and has been used in a limited number of studies (4). However, measurements of creatinine clearance are unlikely to be made in the day-to-day clinical management of RCIN.
The decision to terminate the study following the prespecified, midpoint analysis was prompted by two factors. The first was the significant reduction in the incidence of RCIN in the treatment group and the significant difference in changes in serum creatinine between the groups. We accept that this did not reach the estimated level used for the power calculation and that some of the difference is accounted for by the drop in creatinine in the NAC-treated group rather than a pure reduction in the incidence of RCIN. The second reason for our decision to halt the study was that at the time of the analysis (August 2003) two further studies had been published demonstrating a reduction in RCIN in patients treated with oral NAC and exposed to large (2)and small (3)doses of radiocontrast. We felt it unnecessary and perhaps unjustifiable to continue with the non–NAC-treated control group in the light of the data we had accumulated.
Of those patients who developed RCIN (8 in the control group and 2 in the NAC-treated group) the mean change in creatinine was 0.8 mg/dl (Fig. 1), reflecting a mean change from baseline of 40% (range 27% to 69%), thus demonstrating, in these patients, a substantial deterioration in renal function. No difference was seen in the volume of contrast used or baseline creatinine in those who developed RCIN compared to those who did not (253 ± 178 vs. 226 ± 156 ml, p = 0.65, and 2.0 ± 0.7 vs. 1.8 ± 0.5 mg/dl, p = 0.51, respectively). As we reported, no patient required renal replacement therapy.
- American College of Cardiology Foundation
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