MINERVA ANESTESIOL 2004;70:189-91 Hemofiltration in the prevention of radiocontrast agent induced nephropathy G. MARENZI, A.L. BARTORELLI Aim. The aim of the study was to investigate the Monzino Heart Center, IRCCS, Institute of role of hemofiltration in preventing contrast Cardiology, University of Milan, Milan, Italy nephropathy in patients with renal failure. Methods. We randomized 114 renal failure patients undergoing percutaneous coronary interventions (PCI) to either peri-procedural going PCI, the occurrence of RCN has been hemofiltration or saline hydration. associated with significant in-hospital and Results. Contrast nephropathy occurred in 5% long-term mortality, increased risk of in-hospi- of hemofiltration-treated patients and in 50% tal major adverse cardiac events as well as in controls (P<0.01). In-hospital event rate as with prolonged hospital stay and increased well as in-hospital and 1-year mortality rates 3-5 were lower in patients treated with hemofil- costs of health care . Most of RCN occurs in tration. patients with pre-existing renal insufficiency. Conclusion. In patients with renal failure under- Several strategies have been proposed to going PCI, peri-procedural hemofiltration is provide prophylaxis against RCN. Until recen- effective for the prevention of contrast neph- ropathy, and is associated with improved in- tly, only saline hydration, low osmolality con- hospital and long-term outcome. trast media, and acetylcysteine, an antioxi- dant, have been shown to provide some pro- Key words. Hemofiltration - Angioplasty, tran- sluminal, percutaneous coronary - Kidney tection and to reduce the incidence of RCN. diseases, chemically induced. However, their efficacy in patients with seve- re renal failure who undergo radiographic procedures requiring high contrast volume adiocontrast-induced nephropathy (RCN), is still controversial, and their impact on cli- Rdefined as an absolute or relative increa- nical outcome is unknown. se in serum creatinine concentration occur- Hemofiltration (HF) is a new strategy for ring 48-72 hours after contrast agent expo- the prevention of RCN. In addition to provi- sure, is a frequent complication of percuta- de hemodynamic stability, HF can exert a neous coronary interventions (PCI). Its clini- beneficial effect through other mechanisms, cal course can range from transient eleva- such as high-volume controlled hydration tion in serum creatinine to permanent renal without the risk of fluid overload and lung failure requiring dialysis1,2. In patients under- congestion. Moreover, by resembling glo- merular filtration, HF removes contrast agent from the circulation. This mechanism, along Address reprint requests to: G. Marenzi, MD, Centro Cardiologico Monzino, Via Parea 4, 20138 Milano, Italy. E-mail: with contrast dilution due to replacement [email protected]. fluid infusion, lowers dye concentration in Vol. 70, N. 4 MINERVA ANESTESIOLOGICA 189 MARENZI HEMOFILTRATION IN THE PREVENTION OF RADIOCONTRAST AGENT INDUCED NEPHROPATHY Figure 1. — Possible mechanisms of hemofiltration-asso- Figure 2. — In-hospital and 1-year mortality rates in patients ciated benefit in the prevention of contrast-nephropathy. undergoing prophylactic treatment with hemofiltration as compared with saline hydration (controls). the blood, and possibly reduces kidney expo- HF group and 14% in the saline group sure to its nephrotoxic effects (Figure 1). This (P=0.015), while the cumulative 1-year mor- study investigated the role of HF as a prophy- tality was 10% and 30%, respectively (P=0.01). lactic strategy for the prevention of RCN in high-risk patients undergoing PCI. Discussion and conclusions The results of this study demonstrate that Materials and methods prophylactic HF is an effective and safe stra- In a prospective study we randomized 114 tegy for the prevention of RCN in patients consecutive patients with chronic renal fai- with chronic renal failure who are under- lure (creatinine >2 mg/dl) undergoing PCI to going PCI. Furthermore, in-hospital and 1- either HF (n=58; mean creatinine =3.0±1 year clinical outcomes were also significan- mg/dl) or isotonic saline hydration at a rate of tly improved in comparison to the control 1 ml/kg/hour (n=56; mean creatinine=3.1±1 group. It must be considered that our study mg/dl). HF (fluid replacement rate: 1 000 ml/h patients were at very high risk for RCN and without weight loss) and saline hydration poor clinical outcome1-10. Indeed, all had were started 4-8 hours before coronary inter- severe renal insufficiency (creatinine ranging vention, and continued 18-24 hours after. from 2.1 to 6.3 mg/dl), high volume contra- st exposure, and, in most, one or more addi- Results tional RCN risk factors were present. Despite this high-risk profile, only 5% of the HF-trea- We found that 5% of subjects who received ted patients developed RCN, while it occur- HF experienced a 25% increase in serum red in 50% of control patients. In HF-treated creatinine concentration after PCI, compa- patients, all the primary end-points (morbidity red with 50% of control patients, who recei- and in-hospital and long-term mortality) were ved isotonic-saline hydration (P<0.01). markedly lower than in controls, and were Temporary renal replacement therapy was not different from those reported for patients required in 25% of the control group patients, without chronic renal failure or with chro- and in 3% of HF group patients. In-hospital nic renal failure not complicated by RCN5-7. major adverse event rate was 9% in the HF The precise mechanism of the clinical group, and 52% in the control group benefit observed with HF remains unclear. (P<0.001). Moreover, the in-hospital and one- We do not know whether its hypothetical year mortality rates were significantly lower capability of removing radiocontrast from the among patients who received HF (Figure 2). circulation plays a major role. Beneficial Indeed, in-hospital mortality was 2% in the effects may derive from other factors, such as 190 MINERVA ANESTESIOLOGICA Aprile 2004 HEMOFILTRATION IN THE PREVENTION OF RADIOCONTRAST AGENT INDUCED NEPHROPATHY MARENZI hemodynamic stability, high-volume con- venti di chirurgia coronarica per via percutanea sono trolled hydration, and the general intensity of stati assegnati, con criterio casuale, all’emofiltrazione the care rendered in an Intensive Care Unit. peri-procedurale oppure all’idratazione salina. Risultati. È stata riscontrata una nefropatia da mez- On the other hand, RCN occurring after PCI zo di contrasto nel 5% dei pazienti sottoposti a emo- cannot be ascribed to contrast agent toxicity filtrazione e nel 50% dei controlli (p<0,01). Il tasso di only. We cannot exclude that other factors, incidenza intraospedaliera, nonchè il tasso di morta- namely hemodynamic instability, concomi- lità intraospedaliera e il tasso di mortalità a un anno tant pharmacological therapy, and athe- sono risultati essere inferiori nei pazienti sottoposti a roembolism may have contributed to renal emofiltrazione. Conclusioni. Nei pazienti affetti da insufficienza impairment and influenced the clinical out- renale e sottoposti a interventi di chirurgia coronaria come of our patients. Thus, the combination per via percutanea, l’emofiltrazione peri-procedura- of several positive properties of HF, offering le risulta essere efficace ai fini della prevenzione del- a broad-spectrum renal protective effect, may la nefropatia da mezzo di contrasto; inoltre essa si be a more convincing explanation of our associa a un miglioramento della prognosi intrao- results than that of the action of a single spedaliera e a lungo termine. mechanism, such as removal of contrast Parole chiave: Emofiltrazione - Angioplastica coro- agent. Indeed, when hemodialysis, the most narica - Nefropatia, eziologia - Mezzi di contrasto. efficient form of contrast agent removal, was utilized, no benefit in preventing RCN and associated morbidity was demonstrated7. References It must be emphasized that our positive 1. Rich MW, Crecelius CA. Incidence, risk factors and cli- results were obtained in a very high-risk group nical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older. A of patients undergoing multiple interventions perspective study. Arch Intern Med 1990;150:1237-42. and requiring larger contrast volume compa- 2. McCullough PA, Wolyn R, Rocher LL, Levin RN, O’Neill red to that used during simple diagnostic WW. Acute renal failure after coronary intervention: incidence, risk factors and relationship to mortality. radiographic procedures. The results of this Am J Med 1997;103:368-75. study are not directly applicable to all patients 3. Gruberg L, Mintz GS, Mehran R, Dangas G, Lansky AJ, who are at risk and are exposed to radio- Kent KM et al. The prognostic implications of further renal function deterioration within 48 hours of inter- contrast media for simpler procedures, and ventional coronary procedures in patients with pre- further studies are warranted to identify tho- existent chronic renal insufficiency. J Am Coll Cardiol 2000;36:1542-8. se renal failure patients who are at particularly 4. Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, high-risk and may derive the greatest benefit Best PJ et al. Incidence and prognostic importance of from this preventive strategy. In our study, acute renal failure after percutaneous coronary inter- vention. Circulation 2002;105:2259-64. patients with the higher baseline creatinine 5. Best PJM, Lennon R, Ting HH, Bell MR, Rihal CS, values (≥4 mg/dl) had the greatest positive Holmes DR et al. The impact of renal insufficiency on effect, in terms of long-term survival, from clinical outcomes in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol 2002;39: hemofiltration. Hence, a more selective crite- 1113-9. ria than that used in our study (creatinine >2 6. Gruber L, Mehran R, Dangas G, Mintz GS, Waksman R, Kent KM et al. Acute renal failure requiring dialysis mg/dl) may identify those patients who could after percutaneous coronary interventions. Catheter obtain the maximal benefit from hemofiltra- Cardiovasc Interv 2001;52:409-16.