Prophylaxis of contrast-induced nephropathy in patients with impaired renal function: double-blind comparison of acetylcysteine, theophylline, acetylcysteine + theophylline and placebo

Background

Contrast-induced nephropathy (CIN) is frequently found in ICU patients. Several recent studies have shown a prophylactic effect of acetylcysteine (A) and theophylline (T). The results are contradictory, however, and only one study has so far compared the effects of both agents [1]. Nevertheless, this study did not include a placebo group and was not restricted to patients with impaired renal function.

Aim

To compare the effects of A, T, a combination of A and T (A + T) and placebo (P) in patients with impaired renal function.

Materials and methods

Two hundred and fifty-four patients with serum creatinine ≥ 1.3 mg/dl receiving ≥ 100 ml contrast-medium (CM) were randomised to receive A (600 mg, p.o., b.i.d.; start 24 hours before CM), T (200 mg, i.v., 30 min before CM), A + T, or P. Primary endpoint The incidence of CIN (increase of serum creatinine ≥ 0.5 mg/dl within 48 hours). Secondary endpoint Time course of serum-creatinine. Statistics Chi-square-test and Wilcoxon-test, SAS software version 6.12.

Results

Patients of groups A, T, A + T and P were comparable with regard to baseline creatinine (1.49 ± 0.43 vs 1.53 ± 0.56 vs 1.57 ± 0.40 vs 1.69 ± 0.77 mg/dl; not significant [NS]), amount of CM (192.5 ± 104.3 vs 240.2 ± 149.9 vs 222.7 ± 141.9 vs 207.6 ± 113.6 ml; NS) and incidence of other risk factors (RF) such as diabetes and hypertension. The incidence of CIN was 4/62 (6.5%) in group A, 3/64 (4.7%) in group T, 7/66 (10.6%) in group A + T, and 10/62 (16.1%) in group P. Overall, the incidence was lower under prophylaxis (14/192; 7.3%) than under placebo (10/62, 16.1%; P = 0.0386). Patients of group T had a significantly lower incidence of CIN than patients under placebo (P = 0.0348), whereas neither group A nor group A + T had a lower incidence of CIN than group P.

Compared with baseline, serum creatinine levels significantly increased after 48 hours in group A (1.54 ± 0.39 vs 1.49 ± 0.43 mg/dl; P = 0.00986), group A + T (1.63 ± 0.41 vs 1.57 ± 0.40 mg/dl; P = 0.0075) and group P (1.80 ± 0.85 vs 1.69 ± 0.77 mg/dl; P = 0.00619). However, there was no significant increase in group T (1.56 ± 0.55 vs 1.53 ± 0.56 mg/dl; NS).

Conclusions

In patients with impaired renal function theophylline significantly reduces the incidence of CIN, whereas acetylcysteine alone or in combination with theophylline was not effective.