Table 5.
Different NAC dosing regimen investigated for the reduction of contrast-induced AKI (CI-AKI), with emphasis on the preexistence of CKD, start of treatment and treatment duration in relation to administration of the contrast medium, and NAC dosing and dosage forms
| Study | NAC dose and regimen | CKD | Study design | Type of contrast agenta, ml of contrast agent | Number of participants: overall (receiving NAC) | Effects of NAC |
|---|---|---|---|---|---|---|
| Mostly no preexisting CKD | ||||||
| No favorable effects of NAC | ||||||
| Thiele et al.100 | NAC i.v. 1200 mg bolus before the procedure, then i.v. twice daily after the procedure for 48 h | mostly no CKD | RCT | Low-osmolal, nonionic (Ultravist-iopromide), ∼160–180 ml | 251 (126) | - No effect on occurrence of more than 25% increase of creatinine concentration - No effect on myocardial reperfusion injury -Reduction of oxidized LDL and AOPPs |
| Traub et al.101 | NAC i.v. 3 g over 30 min before contrast, then after contrast 200 mg/h for between 2 h and 15 h | mostly no CKD | RCT | Isovue, Optiray, Visipaque (iopamidol, ioversol, iodixanol; low- and iso-osmolar, nonionic), ∼115 ml | 399 (200) | - No beneficial effects |
| Thayssen et al.102 | NAC p.o. 1200 mg before the procedure, then 1200 mg daily for 48 h | mostly no CKD | RCT | Iso-osmolar, nonionic (Visipaque iodixanol), ∼140–150 ml | 357 (176) | - No effect on occurrence of more than 25% increase of creatinine concentration within 72 h |
| Yang et al.103 | NAC p.o. 600 mg (Hainan Zambon Pharmaceutical Co.) twice daily on the d before and after contrast | Mostly no CKD | RCT | ∼125–130 ml | 627 (157) | - No effect on occurrence of more than 25% increase of creatinine concentration within 72 h |
| Aslanger et al.104 | NAC i.v. and p.o. (1200 mg bolus injection during the procedure, then 1200 mg p.o. twice a d for 48 h after the procedure); or intrarenal and p.o. (600 mg bolus in each renal artery before contrast administration, then 1200 mg p.o. twice a d for 48 h after the procedure) | Mostly no CKD | RCT | Low-osmolal, ionic (Hexabrix ioxaglate), ∼195–205 ml | 312 (108/105) | - No prevention of occurrence of more than 25% increase of creatinine concentration within 72 h postprocedure |
| Carbonell et al.105 | NAC i.v. 600 mg over 30 min twice daily in 4 doses, started at least during 6 h before the procedure | Mostly no CKD | RCT | Low-osmolal, non-ionic (Ultravist iopromide), ∼180–190 ml | 216 (107) | - No prevention of occurrence of more than 25% increase of creatinine or a creatinine increase ≥ 44 μmol/l within 48 h postprocedure |
| Favorable effects of NAC | ||||||
| Kim et al.106 | NAC p.o. 600 mg twice daily on the d before and on the d of the procedure | No CKD | RCT | iodixanol, iobitridol, iopamidol (low- and iso-osmolal, non-ionic) (Ultravist-iopromide), ∼200–215 ml | 166 (80) | - Reduced occurrence of more than 25% increase of cystatin C or a cystatin C increase ≥ 0.5 mg/dl within 48 postprocedure |
| Biernacka-Fialkowska et al.107 | NAC i.v. 600 mg 12 h before and on the morning before the procedure, then on the evening after the procedure and twice the d after | Mostly no CKD | RCT (single blinded) | Low- and iso-osmolal, non-ionic, ∼200 ml | 222 (108) | - Reduced occurrence of more than 25% increase of creatinine or a creatinine increase ≥ 44 μmol/l within 48–72 h postprocedure |
| Marenzi et al.108 | NAC i.v. 600 mg bolus before the procedure, then 600 mg p.o. twice daily for 48 h; or NAC i.v. 1200 mg bolus before the procedure, then 1200 mg p.o. twice daily for 48 h | Mostly no CKD | RCT | Low-osmolal, non-ionic (Omnipaque iohexol), ∼250–270 ml | 352 (115/118) | - Reduced occurrence of more than 25% increase of creatinine within 72 h post-procedure. - Lower number of in-hospital deaths. |
| Preexisting CKD or reduced kidney function | ||||||
| No favorable effects of NAC | ||||||
| Jaffery et al.109 | NAC i.v. 1200 mg bolus, then 200 mg/h for 24 h | Mostly no CKD, ∼25% CKD G3 or higher | RCT | Isotonic, non-ionic (Visipaque iodixanol) ∼160–170 ml | 398 (192) | - No effect on occurrence of more than 25% increase of creatinine concentration within 72 h - Tendency to higher post-procedure cystatin C in the NAC group (P = 0.07) |
| ACT investigators110 | NAC p.o. 1200 mg (powder, Medley, Brazil), 2 doses before the procedure, 2 doses after the procedure every 12 h. | 50% no CKD, ∼43% CKD G3, ∼6% ≥ CKD G4 | RCT | Mostly low-osmolarity, ∼100 ml | 2308 (1172) | - No effect on occurrence of more than 25% increase of creatinine concentration within 48–96 h, also not if stratified into CKD stage subgroups. |
| Weisbord et al.111 | NAC p.o., 1200 mg (capsuled powder, noncommercial study preparation) 1 dose ∼1 h before the procedure, then again 1 dose 1 h after the procedure, then twice daily for the following 4 d after the procedure. | In median CKD 3a | RCT | Low- and iso-osmolal, non-ionic, ∼85 ml | 4993 (2495) | - No prevention of death, need for dialysis, or persistent decline in kidney function at 90 days - No prevention of occurrence of more than 25% increase of creatinine or a creatinine increase ≥ 44 µmol/L between day 3 and 5 post-procedure |
| Reinecke et al.112 | NAC p.o. 600 mg on the evening and morning before the procedure, and on the evening and morning thereafter. | In mean ∼CKD G3a | RCT | Iso-osmolar nonionic (Ultravist iopromide), ∼190–200 ml | 286 (146) | - No reduction of eGFR decline 72 h post-procedure |
| Khatami et al.113 | NAC p.o. 600 mg twice daily from the d before the procedure, continued for 3 d; or NAC i.v. 1200 mg 30 min before the procedure | In mean ∼CKD G3b. | RCT | Iso-osmolar, nonionic (Visipaque iodixanol), ∼110–120 ml | 434 (149/145) | - No effect on occurrence of more than 25% increase of creatinine or a creatinine increase ≥ 44 μmol/l 48 h postprocedure. |
| Brueck et al.114 | NAC i.v. 600 mg 24 h and 1 h before contrast | in median ∼CKD G3b | RCT | low-osmolal, non-ionic (Ultravist iopromide), ∼110 ml | 397 (199) | - No prevention of AKI |
| Ferrario et al.115 | NAC p.o. 600 mg, 2 doses on the d before and 1 dose on the morning before the procedure, 1 dose on the evening after the procedure | In mean ∼CKD G3b. | RCT | Iso-osmolar, nonionic (Visipaque iodixanol), ∼170–180 ml. | 200 (99) | - No prevention of occurrence of more than 25% increase of creatinine or a creatinine increase ≥ 44 μmol/l within 72 h postprocedure. |
| Erturk et al.116 | NAC i.v. 2400 mg over 1 h before the procedure, then 4800 mg within 4–6 h after the procedure; or NAC p.o. 1200 mg (Asist sachet, Husnu Arsan Company) 2 doses within 24 h before the procedure and 4 doses within 48 h after the procedure | 92.5% CKD G3; 7.5% CKD G4 | RCT | Low-osmolal, nonionic (Ultravist iopromide), ∼125 ml | 315 (105/105) | - No prevention of occurrence of more than 25% increase of creatinine or a creatinine increase ≥ 44 μmol/l at 48 h postprocedure - No prevention of cystatin C increase. - No reduction of death or need for dialysis after 30 d and 1 yr. |
| Favorable effects of NAC | ||||||
| Hsu et al.117 | NAC i.v. 600 mg over 1 h before contrast | In mean ∼CKD G3a | Matched case-control | Low-osmolar nonionic (Omnipaque iohexol, Xenetix iobitridol, Ultravist iopromide), ∼90 ml | 209 (106) | - Reduced eGFR decline 48–72 h post-procedure. - No effect on need for dialysis. |
| Kay et al.118 | NAC p.o. 600 mg (Fluimucil, Zambon), 2 doses on the d before the procedure, then 1 more dose before and 1 dose after the procedure. | In median ∼CKD G3 | RCT | Low-osmolal, nonionic (iopamidol), ∼120–130 ml | 200 (102) | - Reduced occurrence of more than 25% increase of creatinine concentration within 48 h postprocedure. - Effect persisted for at least 7 d - Shorter length of hospitalization. |
| Webb et al.,119 Levin et al.120 |
NAC i.v. 500 mg over 15 min within 1 h before start of the procedure | In median ∼CKD G3 | RCT | Low-osmolar, nonionic (Optiray ioversol), ∼120 mL | 447 (220) | - No prevention of GFR decline or occurrence of more than 25% increase of creatinine or a creatinine increase ≥ 44 μmol/l between d 2 and 8 postprocedure. - Subgroup analysis of patients with urine samples available (n = 125) showed attenuation of contrast-induced albumin excretion. |
| Tepel et al.121 | NAC p.o. 600 mg, 2 doses on the d before and 1 dose on the morning before the procedure, 1 dose on the evening after the procedure | in mean ∼CKD G4 | RCT | Low-osmolal, nonionic (Ultravist iopromide), 75 ml | 83 (41) | - Reduced incidence of a creatinine increase ≥ 44 μmol/l 48 h postprocedure. |
AKI, acute kidney injury; AOPP, advanced oxidation protein product; CKD, chronic kidney disease; CKD G×, indicated respective (×) stage of CKD; eGFR, estimated glomerular filtration rate; LDL, low-density lipoprotein; NAC, N-acetylcysteine; RCT, randomized controlled trial,.
a
The classification of the contrast-agent with respect to osmolality is given as classified in the original publication if reported there.