N-acetylcysteine prophylaxis significantly reduces the risk of radiocontrast-induced nephropathy: comprehensive meta-analysis.

The objectives of this study was to assess the overall effect of N-acetylcysteine (NAC) in preventing radiocontrast-induced nephropathy (RCIN) using all available data in the literature. RCIN is associated with increased morbidity and mortality. Existing randomized trials of NAC are small and show inconsistent results. Prior meta-analyses do not include data from the most current studies. We used standard search protocols to identify all published articles and abstracts of prospective trials using NAC with fluid hydration compared to hydration alone in patients with chronic renal insufficiency undergoing contrast procedures. A rise in serum creatinine by 0.5 mg/dl or 25% above baseline at 48-72 hr after contrast exposure was used as the primary outcome. We identified 14 trials of NAC with 1,584 patients published as full-text articles. Using a random-effects model, the use of oral NAC resulted in a significant reduction in the risk for developing RCIN (RR = 0.57; 95% CI = 0.37-0.84; P = 0.01). This finding did not significantly change in a fixed-effect model (RR = 0.55; 95% CI = 0.42-0.73) or when the data were reanalyzed using only randomized trials in all forms (i.e., articles and abstracts; RR = 0.67; 95% CI = 0.47-0.95). We identified only one important difference between the positive and the negative studies: the cumulative exposure to contrast media (174 vs. 152 ml). Metaregression did not show a significant relationship between contrast volume and the RR of developing RCIN (P > 0.10). In the trials showing benefit for NAC, the treated patients' postprocedure creatinine unexpectedly decreased by 0.21 mg/dl (95% CI = 0.33-0.08). Prophylaxis with NAC significantly reduces the risk for RCIN. The reasons for improvement in serum creatinine in patients treated with NAC are unclear, but may include improved renal blood flow due to NAC and/or vigorous hydration.     

Prospective randomized study of N-acetylcysteine, fenoldopam, and saline for prevention of radiocontrast-induced nephropathy.

The objective of this study was to compare the efficacy of N-acetylcysteine (NAC), fenoldopam, and saline in preventing radiocontrast-induced nephropathy (RCIN) in high-risk patients undergoing cardiovascular procedures. We prospectively enrolled 123 patients who were scheduled for cardiovascular procedures and had a baseline creatinine > 1.6 mg/dl or creatinine clearance of < 60 ml/min. Patients were randomly assigned to receive either saline (0.45% normal saline at 1 cc/kg) for 12 hr before and 12 hr after the procedure, or fenoldopam (0.1 microg/kg/min) plus saline for 4 hr prior and 4 hr after the procedure, or NAC orally (600 mg) plus saline every 12 hr for 24 hr prior and 24 hr after the procedure. All the patients received low-osmolality nonionic contrast. RCIN was defined as an increase in creatinine level > 0.5 mg/dl after 48 hr. The incidence of RCIN was 17.7% in the NAC group, 15.3% in the saline group, and 15.7% in the fenoldopam group (P = 0.919). Of the 20 patients who developed RCIN, 2 required dialysis. Serum creatinine decreased after 48 hr (vs. baseline) in 38% patients in the NAC group, 18% in the fenoldopam group, and 15% in the saline group. In patients with chronic renal insufficiency, NAC or fenoldopam offered no additional benefit over hydration with saline in preventing RCIN.     

Oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy following coronary angiography. A randomized controlled trial and review of the current literature.

AIMS: To determine laboratory and clinical benefit of oral acetylcysteine, as an adjunct to saline hydration, in chronic renal insufficiency patients undergoing coronary angiography. METHODS AND RESULTS: We prospectively studied 80 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration 2.0+/-0.39mg/dl), who underwent coronary angiography with or without intervention. Patients were randomly assigned to receive either acetylcysteine (600mg orally t.i.d.) or placebo, in addition to intravenous 0.45% saline (1ml/kg of body weight per hour), 12h prior to and after coronary angiography. There was an increase of >/=0.5mg/dl in the serum creatinine concentration 48h after coronary angiography in seven of the 80 patients (9%): in four of the 41 patients (10%) in the acetylcysteine group and in three of the 39 patients (8%) in the placebo group (P=0.52). The incidence of in-hospital adverse clinical events (acetylcysteine, 5% vs placebo, 8%, P=0.47) and the length of hospital stay [acetylcysteine, median (interquartile range) 4 (2-4) days vs placebo, 2 (2-4) days, P=0.44] did not differ significantly between the two treatment groups. CONCLUSION: Our findings do not support routine prophylactic administration of oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy in chronic renal insufficiency patients undergoing coronary angiography.     

Effectiveness of acetylcysteine in prevention of contrast nephropathy

BACKGROUND: Acetylcysteine may provide prophylaxis against contrast nephropathy (CN) in some patients. Its benefit may vary according to the characteristics of patients and contrast used. The objective is to evaluate the effectiveness of oral acetylcysteine in preventing CN after coronary procedures in our practice. METHODS: We prospectively studied 397 patients with a creatinine level equal to or above 1.3 mg/dl, diabetes mellitus, or 70+ years of age who underwent a coronary procedure. Patients were randomly assigned to receive either acetylcysteine or placebo and 0.9% saline before and after the contrast agent. High- or low-osmolality contrast was used according to the discretion of the interventional cardiologist. Serum creatinine was measured before and 24 to 48 hours after the procedure. RESULTS: An increase of greater than or equal to 25% in the baseline creatinine level 24 to 48 hours after the procedure occurred in 14 (7.1%) of 196 acetylcysteine patients and in 17 (8.4%) of 201 placebo patients (p=0.62). In the acetylcysteine group, the mean baseline serum creatinine concentration was 1.30+/-0.56 mg/dl and increased 0.076+/-0.21 mg/dl 24 to 48 hours after administration of contrast, whereas in the placebo group, it was 1.27+/-0.51 mg/dl and increased 0.101+/-0.28 mg/dl (p=0.33). In the subgroup with estimated baseline creatinine clearance <60 ml/minute, no difference was found in the incidence of CN (9.1% in the acetylcysteine group; 11.7% in the placebo; p=0.66). By multivariate analysis, left ventricular ejection fraction less than or equal to 40%, volume of contrast >200 ml, and estimated creatinine clearance (but not acetylcysteine) were related to CN. CONCLUSIONS: Oral acetylcysteine was not effective as a prophylactic treatment against CN for patients with a potential risk and submitted to coronary angiographic procedures with predominantly high-osmolality contrast.     

N-Acetylcysteine versus fenoldopam mesylate to prevent contrast agent-associated nephrotoxicity

OBJECTIVES: We performed a study to assess the efficacy of fenoldopam mesylate (a specific agonist of the dopamine-1 receptor) as compared with N-acetylcysteine (NAC) in preventing contrast agent-associated nephrotoxicity (CAN). BACKGROUND: Prophylactic administration of NAC, along with hydration, prevents CAN in patients with chronic renal insufficiency who are undergoing contrast media administration. Preliminary data support the hypothesis that fenoldopam might be as effective as NAC. METHODS: One hundred ninety-two consecutive patients with chronic renal insufficiency, referred to our institution for coronary and/or peripheral procedures, were assigned randomly to receive 0.45% saline intravenously and NAC (1,200 mg orally twice daily; NAC group; n = 97) or fenoldopam (0.10 microg/kg/min; fenoldopam group; n = 95) before and after a nonionic, iso-osmolality contrast dye administration. RESULTS: Baseline creatinine levels were similar in the two groups: NAC group = 1.72 mg/dl (interquartile range, 1.55 to 1.90 mg/dl) and fenoldopam group = 1.75 mg/dl (interquartile range, 1.62 to 2.01 mg/dl) (p = 0.17). An increase of at least 0.5 mg/dl of the creatinine concentration 48 h after the procedure occurred in 4 of 97 patients (4.1%) in the NAC group and in 13 of 95 patients (13.7%) in the fenoldopam group (p = 0.019; odds ratio 0.27; 95% confidence interval 0.08 to 0.85). The amount of contrast media administration was similar in the two groups (NAC group = 160 +/- 82 ml; fenoldopam group = 168 +/- 104 ml; p = 0.54). CONCLUSIONS: N-acetylcysteine seems to be more effective than fenoldopam in preventing CAN.     

Acetylcysteine and contrast agent-associated nephrotoxicity

OBJECTIVES: Prophylactic acetylcysteine along with hydration seems to be better than hydration alone in preventing the reduction in renal function induced by a contrast dye. BACKGROUND: Contrast media can lead to acute renal failure that may occasionally require hemodialysis. METHODS: One hundred eighty-three consecutive patients with impairment of renal function, undergoing coronary and/or peripheral angiography and/or angioplasty, were randomly assigned to receive 0.45% saline intravenously and acetylcysteine (600 mg orally twice daily; group A, n = 92) or 0.45% saline intravenously alone (group B, n = 91) before and after nonionic, low-osmolality contrast dye administration. RESULTS: The baseline serum creatinine concentrations were similar (1.5 +/- 0.4 mg/dl in group A vs. 1.5 +/- 0.4 mg/dl in group B; p = 0.37). An increase of > or =25% in the baseline creatinine level 48 h after the procedure occurred in 6 (6.5%) of 92 patients in group A and in 10 (11%) of 91 patients in group B (p = 0.22). In the subgroup with a low (<140 ml) contrast dose, renal function deterioration occurred in 5 (8.5%) of 60 patients in group B and in 0 of 60 patients in group A (p = 0.02; odds ratio [OR] 0.44, 95% confidence interval [CI] 0.35 to 0.54). In the subgroup with a high contrast dose, no difference was found (5/31 vs. 6/32 patients, p = 0.78). By multivariate analysis, the amount of contrast agent, but not the treatment strategy, was a predictor of the occurrence of contrast dye-associated nephrotoxicity (OR 2.58, 95% CI 1.1 to 4.9; p = 0.035). CONCLUSIONS: In patients with reduced renal function undergoing angiography and/or angioplasty, the amount of contrast agent, but not the administration of prophylactic acetylcysteine, was a predictor of renal function deterioration. Prophylactic acetylcysteine might provide better protection than hydration alone, only when a small volume of contrast agent is used.     

Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure

OBJECTIVES: We sought to evaluate the efficacy of the antioxidant acetylcysteine in limiting the nephrotoxicity after coronary procedures. BACKGROUND: The increasingly frequent use of contrast-enhanced imaging for diagnosis or intervention in patients with coronary artery disease has generated concern about the avoidance of contrast-induced nephrotoxicity (CIN). Reactive oxygen species have been shown to cause CIN. METHODS: We prospectively studied 121 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration 2.8 +/- 0.8 mg/dl) who underwent a coronary procedure. Patients were randomly assigned to receive either acetylcysteine (400 mg orally twice daily) and 0.45% saline intravenously, before and after injection of the contrast agent, or placebo and 0.45% saline. Serum creatinine and blood urea nitrogen were measured before, 48 h and 7 days after the coronary procedure. RESULTS: Seventeen (14%) of the 121 patients had an increase in their serum creatinine concentration of at least 0.5 mg/dl at 48 h after administration of the contrast agent: 2 (3.3%) of the 60 patients in the acetylcysteine group and 15 (24.6%) of the 61 patients in the control group (p < 0.001). In the acetylcysteine group, the mean serum creatinine concentration decreased significantly from 2.8 +/- 0.8 to 2.5 +/- 1.0 mg/dl (p < 0.01) at 48 h after injection of the contrast medium, whereas in the control group, the mean serum creatinine concentration increased significantly from 2.8 +/- 0.8 to 3.1 +/- 1.0 mg/dl (p < 0.01). CONCLUSIONS: Prophylactic oral administration of the antioxidant acetylcysteine, along with hydration, reduces the acute renal damage induced by a contrast agent in patients with chronic renal insufficiency undergoing a coronary procedure.     

Sodium Bicarbonate versus Sodium Chloride and Oral N‐Acetylcysteine for the Prevention of Contrast‐Induced Nephropathy in Advanced Chronic Kidney Disease

Introduction: Contrast‐induced acute kidney injury (CI‐AKI) is one of the leading causes of hospital‐acquired acute kidney injury. Multiple clinical studies have proposed several preventive strategies. Aims: To examine the efficacy of sodium bicarbonate compared with sodium chloride and oral N‐acetylcysteine (NAC) for preventive hydration after cardiac catheterization. Methods: We conducted a prospective, single‐center trial. Patients with chronic kidney disease (CKD) stage III–IV undergoing cardiac catheterization were allocated to receive either an infusion of 0.9% sodium chloride and oral NAC or 154 mEq/L sodium bicarbonate. Main: Outcome measure CI‐AKI, defined as an increase of 25% or 0.3 mg/dL or more in plasma creatinine within 2 days of contrast administration. Results: Ninety‐three patients were allocated to one of the two groups: 42 patients in the saline plus NAC group and 51 patients in the bicarbonate group. There were no statistically significant differences between the groups in the most important clinical and procedural characteristics. Baseline plasma creatinine levels, estimated glomerular filtration rate, incidence of diabetes mellitus, hypertension, congestive heart failure, and contrast medium volume were similar. Mean plasma creatinine concentration was 1.76 ± 0.54 mg/dL in the saline and NAC group and 1.9 ± 1 mg/dL in the bicarbonate group (P = 0.23). The rate of CI‐AKI was 9.8% in the bicarbonate group and 8.4% in the saline plus NAC group. No patient required renal replacement therapy. Conclusion: Hydration with sodium bicarbonate is not more effective than hydration with sodium chloride and oral NAC for prophylaxis of CI‐AKI in patients with CKD stage III–IV undergoing cardiac catheterization.     

N‐Acetylcysteine in Preventing Contrast‐Induced Nephropathy Assessed by Cystatin C

Aims: Prophylactic oral N‐acetylcysteine (NAC) has been widely used for prevention of contrast‐induced nephropathy (CIN). However, clinical studies have not been demonstrating this effect consistently because of evidence that NAC can alter serum creatinine levels without affecting glomerular filtration rate (GFR). We investigated NAC for the prevention of CIN by monitoring creatinine and cystatin C. Methods: We enrolled 113 patients (49 patients in NAC group and 64 patients in control group) with normal to subnormal GFR who were scheduled for cardiovascular procedures. Patients in NAC group receive acetylcysteine 600 mg twice a day, on the day before and on the day of cardiovascular procedure. All patients received a periprocedural intravenous infusion ("volume expansion") of 1 ml/kg/h with 0.45% saline for 24 h (12 h before and 12 h after exposure to contrast medium). Serum cystatin C and creatinine levels were measured before and at 12, 24, and 48 h after procedure. Results: The incidence of cystatin C‐based CIN was 28.5% (n = 14) in NAC and 23.4% (n = 15) in control group (p = 0.663) and serum creatinine‐based CIN was 12.2% (n = 6) in NAC and 17.2% (n = 11) in control group (P= 0.468). In this study, oral NAC had no effect on the prevention of CIN in patients undergoing cardiovascular procedures. Conclusion: In this study, oral NAC administration does not reduce neither the incidence of cystatin C‐based CIN nor serum creatinine‐based CIN in patients undergoing cardiovascular procedures.     

Absence of nephro-protective effect of acetylcysteine in patients with chronic renal failure investigated by coronary angiography

Recent studies have suggested that an oral dose of acetylcysteine could play a prophylactic role in the prevention of nephrotoxicity from iodine contrast media in patients affected by chronic renal failure. Between June 2001 and September 2002 we selected 120 patients with a basal plasma creatinine level greater than 1.36 mg/dl investigated by coronary angiography. The treatment group included 60 patients who received 600 mg of acetylcysteine in the morning and evening before the day of the examination together with intravenous saline hydration. The control group patients received hydration alone. The clinical characteristics of the groups were comparable as well as the basal plasma creatinine level: 2.01+/-1.1 mg/dl in the acetylcysteine group and 1.81+/-0.69 in the control group. The plasma creatinine level was measured 24 and 48 hours after coronary angiography. The respective changes in plasma creatinine level at 24 and 48 hours were 0.12+/-0.29 and 0.02+/-0.29 mg/dl in the acetylcysteine group and 0.06+/-0.29 and 0.07+/-0.43 mg/dl in the control group (NS). Acute renal failure caused by the contrast medium, defined by an increase of 25% in the plasma creatinine level compared to the basal value, occurred in 3 patients from the acetylcysteine group and 2 patients from the control group. The only predictive factor for acute renal failure was the quantity of contrast medium (316+/-141 vs 173+/-115 ml, p<0.05). In conclusion, acute renal failure caused by contrast medium is rare in sufficiently hydrated patients with moderate chronic renal failure when a low dose of contrast medium is used. Our study does not confirm a prophylactic effect of acetylcysteine in the prevention of nephrotoxicity from contrast media following coronary angiography in patients with moderate chronic renal failure.     

Oral acetylcysteine does not protect renal function from moderate to high doses of intravenous radiographic contrast.

The use of radiographic contrast during cardiac catheterization can cause acute renal failure with an increase in morbidity and mortality. Prophylactic acetylcysteine plus intravenous hydration have been shown to prevent contrast-induced nephropathy (CIN) in patients with chronic renal failure undergoing computed tomography scan, who receive low doses of intravenous contrast. Whether the use of prophylactic acetylcysteine can decrease the incidence of CIN when larger doses of contrast are used remains to be determined. We sought to evaluate whether the prophylactic administration of acetylcysteine plus intravenous hydration is superior to intravenous hydration alone in prevention of CIN in patients with chronic renal failure undergoing cardiac catheterization and receiving moderate to high doses of intravenous contrast (> 1 cc/kg). Seventy-three consecutive patients with renal insufficiency who received intravenous hydration and 600 mg of acetylcysteine twice a day 24 hr before and the day of the cardiac catheterization were compared with 106 consecutive patients who received hydration alone. Baseline and 48-hr serum creatinine concentrations were compared between the two groups before and after cardiac catheterization. Multivariate and univariate analysis were performed to assess the effects of acetylcysteine and other clinical variables in the change of serum creatinine after the procedure. Both groups had comparable clinical characteristics and received similar volumes of intravenous hydration. The volume of contrast used was similar for the two groups (2.2 +/- 1.7 vs. 2.3 +/- 1.5 cc/kg; P = 0.67). A mean change in serum creatinine of 0.17 +/- 0.54 mg/dl for the acetylcysteine group vs. 0.19 +/- 0.40 mg/dl for the control group (P = 0.77) was observed at 48 hr. The incidence CIN was 13% in the acetylcysteine vs. 12% in the control group (P = 0.84). Acetylcysteine, whether analyzed with multivariate or univariate analysis, failed to demonstrate a significant effect in the change of serum creatinine after cardiac catheterization. In patients with chronic renal insufficiency, acetylcysteine in a dose of 600 mg twice a day before and after cardiac catheterization, along with intravenous fluids, is as effective as fluids alone in the prevention of CIN when moderate to high doses of contrast are used.     

Gender as a risk factor for contrast nephropathy: effects of hydration and N-acetylcysteine

BACKGROUND: In a few studies, N-acetylcysteine has been shown to prevent contrast-induced nephropathy in patients with chronic, stable renal failure undergoing elective procedures. Other studies have shown variable outcomes. Furthermore, the majority of prior studies have mainly studied men, and gender as a risk factor has not been studied. HYPOTHESIS: The study sought to evaluate the effectiveness of N-acetylcysteine and hydration in unselected patients with both acute and stable renal insufficiency (RI) undergoing urgent or elective cardiac or peripheral angiography. METHODS: We evaluated records of 146 patients with RI undergoing angiography. We compared patients receiving periprocedure hydration and acetylcysteine with patients who were only hydrated or received no pretreatment. We evaluated the 48-h change in serum creatinine between groups and further analyzed the effect of hydration and gender on outcomes. RESULTS: Demographics and baseline creatinine were similar between groups. Post procedure, the creatinine increased significantly in both groups, but less so in the acetylcysteine group (control: 0.35 +/- 0.08 mg/dl; acetylcysteine: 0.14 +/- 0.04 mg/dl, p < 0.05). When the control group was further stratified by hydration, the increase in creatinine for the hydrated patients was only 0.17 +/- 0.10 mg/dl compared with 0.54 +/- 0.12 mg/dl in patients with inadequate hydration. In the control group, women were more likely to receive no preprocedural hydration (59 vs. 40%), had a bigger rise in creatinine, received less protection from hydration alone, but were equally well protected by hydration plus acetylcysteine. In the acetylcysteine group, change in creatinine for women was minimal (+ 0.14 +/- 0.07 mg/dl) and not different from men (+ 0.15 +/- 0.05). CONCLUSION: Unselected patients with acute and chronic RI had no benefit from acetylcysteine beyond that seen with hydration alone. Gender may be a risk factor for contrast-induced nephropathy, with hydration offering less protection in women. Acetylcysteine (with hydration) seems to minimize the gender difference.     

Prevention of contrast‐induced acute kidney injury in patients with stable chronic renal disease undergoing elective percutaneous coronary and peripheral interventions: Randomized comparison of two preventive strategies

Objective : We compared use of intravenous (IV) normal saline (NS) to sodium bicarbonate (NaHCO₃) with or without oral N‐acetylcysteine (NAC) for prevention of contrast‐induced acute kidney injury (CI‐AKI). Background : CI‐AKI is associated with significant adverse clinical events. Use of NAC has produced variable results. Recently, intravenous hydration with NaHCO₃ for CI‐AKI prophylaxis has been adopted as standard treatment for patients with stable chronic renal disease undergoing catheterization procedures. Methods : We prospectively enrolled 320 patients with baseline renal insufficiency scheduled to undergo catheterization. Patients were randomly assigned to receive either IV NS ± NAC (n = 161) or IV dextrose 5% in water containing 154 mEq/l of NaHCO₃ ± NAC (n = 159). IV NS was administered at 1 ml/kg body weight for 12 hr preprocedure and 12 more hr postprocedure. IV NaHCO₃ was administered at 3 ml/kg body weight for 1 hr preprocedure followed by 1 ml/kg body weight postprocedure. A 1,200 mg oral dose of NAC was given 2–12 hr preprocedure and 6–12 hr postprocedure in 50% of patients in each study arm. CI‐AKI was defined as an increase of >0.5 mg/dl or >25% above baseline creatinine. Results : Overall incidence of CI‐AKI was 10.3%. There was no significant difference in incidence among the two groups (NS ± NAC 11.8% vs. NaHCO₃ ± NAC 8.8%, p = ns). Incidence of CI‐AKI increased with increasing age (p = 0.001), contrast agent use >3 ml/kg body weight (p = 0.038) and diuretic use (p = 0.005). Conclusion : Incidence of CI‐AKI was no different in the NaHCO₃ group compared to NS group, and NAC did not reduce CI‐AKI in the two study arms. © 2011 Wiley Periodicals, Inc.     

Acetylcysteine, coronary procedure and prevention of contrast-induced worsening of renal function: which benefit for which patient?

OBJECTIVES: This study was designed to determine whether acetylcysteine could provide a protective effect on renal function in a population of patients with normal renal function or mild to moderate chronic renal failure, usually referred for a coronary procedure. BACKGROUND: Contrast-induced nephropathy is a well-recognized complication of coronary angiography. Recent studies suggest that saline hydration and acetylcysteine reduce the incidence of contrast-induced worsening of renal function in patients with pre-existing chronic renal failure who are undergoing computed tomography examinations. METHODS: One hundred eight patients were blindly and randomly assigned to receive either acetylcysteine or placebo before and after administration of contrast agent in association with a moderate hydration protocol. Serum creatinine and urea nitrogen were measured before and 24 hours after coronary procedure. RESULTS: The mean serum creatinine concentration remained unchanged 24 hours after contrast agent administration in both groups: from 1.04 +/- 0.26 to 1.03 +/- 0.29 mg/dl in the acetylcysteine group and from 1.16 +/- 1.1 to 1.06 +/- 0.41 mg/dl in the control group (p = 0.29, for the comparison between two groups, NS). We divided the population into 3 subgroups according to their creatinine clearance: no significant change of serum creatinine concentration was observed in patients with normal renal function nor in patients with pre-existing mild to moderate chronic renal failure in both groups. There was no significant difference for the incidence of contrast-induced nephropathy between both groups (2 of the 53 patients in the acetylcysteine group and 3 of the 51 patients in the placebo group, p = 0.98, NS). CONCLUSIONS: Our data do not support the systematic use of acetylcysteine before a coronary procedure in patients with normal renal function or mild to moderate chronic renal failure, to prevent contrast-induced nephropathy.     

Efficacy of Ascorbic Acid,N‐Acetylcysteine,or Combination of Both on Top of Saline Hydration versus Saline Hydration Alone on Prevention of Contrast‐Induced Nephropathy: A Prospective Randomized Study

Background

Antioxidant drugs such as N‐acetylcysteine (NAC) and ascorbic acid have been evaluated in interventional studies to prevent contrast‐induced nephropathy (CIN), however, there are limited data on comparing either or both, with background of standard intravenous saline hydration versus the standard intravenous saline hydration alone in preventing CIN.

Methods

We conducted a single‐center randomized trial among patients undergoing coronary angiography or percutaneous coronary intervention who had serum creatinine ≥ 1.3 mg/dL or were on diabetes mellitus medication. Eligible patients were randomly assigned to one of the following 4 groups: (1) NAC, (2) ascorbic acid, (3) combination of both drugs, and (4) control group. Additionally, all the groups received the standard intravenous saline hydration. Creatinine was measured 4–5 days after procedure.

Results

A total of 243 patients were randomized; 62 to NAC, 57 to ascorbic acid, 58 to both drugs, and 66 to placebo. The development of 0.5 mg/dL absolute increase of serum creatinine, 25% relative decrease of creatinine clearance, or either (CIN) were measured in the ascorbic acid group (3.6% for all), NAC group (6.8%, 3.4%, 8.5%, respectively), combined group (5.5%, 5.5%, 9.1%, respectively), and control group (6.2%, 6.2%, 7.7%, respectively). None of these differences were significant (P = 0.896 for serum creatinine, P = 0.863 for creatinine clearance, and P = 0.684 for CIN).

Conclusions

In a cohort of patients at risk of developing CIN, we could not detect any significant benefit of the use of ascorbic acid, NAC, or a combination of both drugs over the standard hydration regimen in preventing CIN. (J Interven Cardiol 2013;26:90–96)

     

Loss of systemic endothelial function post-PCI

Loss of endothelial function (LEF) post-PCI may contribute to both acute and long-term complications. A protective effect of BNP on endothelium was suggested previously. Flow-mediated vasodilation (FMD) of the brachial artery, as well as plasma levels of endothelin, BNP, Pro BNP and corin were measured before and following routine PCI. 49 patients with normal baseline endothelial function were recruited. 30 patients developed LEF and were randomized to i.v. nesiritide (the commercially available recombinant form of human BNP) or saline infusion for 3 h. Patients who developed LEF post-PCI had reduced baseline plasma corin levels and their BNP/ProBNP ratio was reduced after the procedure. Nesiritide infusion significantly improved FMD both immediately (Nesiritide versus saline: 2.87+/-0.78% versus 0.51+/-0.25%, P=0.007) and 24 h after the treatment (2.52+/-0.69% versus 0.72+/-0.32%, P=0.025). The elevated plasma ET-1 was reduced by Nesiritide (0.38+/-0.11 fmol/ml 24 h post-PCI versus 0.16+/-0.02 fmol/ml 24 h post BNP, P=0.047), but remained unchanged in saline group (0.39+/-0.21 fmol/ml versus 0.42+/-0.23 fmol/ml, P=0.749). Systemic LEF post-PCI is a frequent event. It may be related to impaired cleavage of ProBNP to BNP. Short-term i.v. nesiritide improves systemic LEF post-PCI.     

Abbreviated dosing of N-acetylcysteine prevents contrast-induced nephropathy after elective and urgent coronary angiography and intervention

BACKGROUND AND HYPOTHESIS: Several studies have utilized low-dose regimens of N-acetylcysteine (NAC) for 48 hours to prevent contrast-induced nephropathy (CIN) after cardiac catheterization (cath) and percutaneous coronary intervention (PCI). A lengthy pretreatment period with NAC may not be feasible in urgent situations. The purpose of this study was to assess the efficacy of an abbreviated, higher dose regimen of NAC for the prevention of CIN after elective and urgent coronary angiography (cath) and/or percutaneous coronary intervention (PCI). METHODS: We prospectively evaluated 80 patients referred for elective or urgent cath and/or PCI with stable chronic renal insufficiency (creatinine clearance <50 cc/min). Patients were randomized to: NAC 1000 mg PO 1 hour before cath/PCI and 4 hours later, or placebo. All patients received hydration (0.9% saline) before and after cath/PCI (minimum total volume > or = 1500 mL). CIN was defined as an increase of Cr > or = 0.5 mg/dL or > or = 25% 48 hours after cath/PCI. RESULTS: CIN occurred in 3 of 36 (8%) patients of the NAC group vs. 11 of 44 (25%) in the placebo group (P = 0.051; OR 3.7, 95% CI 0.94-14.4). Serum creatinine (mean +/- SD) remained stable in the NAC group after cath/PCI (2.02 +/- 0.56 vs. 2.10 +/- 0.81 mg/dL; P = 0.34), but increased after cath/PCI in the placebo group (1.93 +/- 0.53 vs. 2.10 +/- 0.74 mg/dL; P < 0.01). CONCLUSIONS: An abbreviated, higher dose regimen of NAC prevents the rise of serum creatinine 48 hours after cath/PCI, and may prevent CIN after cath/PCI.     

Use and efficacy of saline hydration and N-acetyl cysteine to prevent contrast-induced nephropathy in low-risk populations undergoing coronary artery angiography

Contrast-induced nephropathy (CIN) is most commonly defined as acute renal failure occurring within 48-72 h of exposure to an intravascular radiographic contrast medium that is not attributable to other causes. In the international literature, a 25% increase in serum creatinine levels or an increase in absolute values of 0.5 mg/dl from baseline has been suggested to define CIN. The reported incidence of CIN varies widely, ranging from 2 to 50%. This variability results from differences in the presence or absence of risk factors. With a retrospective analysis we evaluated the use of saline hydration plus N-acetyl cysteine (NAC) to prevent CIN in a low-risk population of patients undergoing coronary artery angiography compared with an historic low risk group not treated. From January 2009 to December 2009, 152 consecutive patients who underwent coronary artery angiography with a low osmolarity contrast agent were enrolled in our study, and compared with an historic control group consisting of 172 low-risk patients. Nephrotoxic drugs such as diuretics, ACE-I and ARBs were stopped at least 24 h before the procedure. Inclusion criteria to define low-risk population were the absence of: diabetes, age >65 years, or baseline creatinine >1.4 mg/dl. We have treated group A (152 patients, 47.3%) with a saline hydration (1 ml/kg/h) plus N-acetyl cysteine 600 mg 12 h before and 12 h after the procedure; group B (group control of 170 patients, 52.7%) were not treated. The overall incidence of CIN was 7.1% (23 patients). In particular, the incidence of CIN was 2.6% (4 patients) in the group A and 11.2% (19 patients) in the group B (p = 0.002). In the multivariate analysis, including risk factor such as age, hypertension, hypercholesterolemia, current smoking habit baseline creatinine level, contrast index and hydration, the last variable was the only one inversely correlated independently with the incidence of CIN (p = 0.001). In conclusion, intravenous hydration with saline and NAC is an effective and low cost tool in preventing CIN in patients undergoing coronary artery angiography, and, according to the current guidelines, should be used in all high-risk patients for CIN. Our results show that even in patients at low risk, hydration with saline 0.9% plus NAC is useful and significantly reduces the incidence of CIN.     

Standard vs double dose of N-acetylcysteine to prevent contrast agent associated nephrotoxicity.

AIMS: Prophylactic administration of N-acetylcysteine (NAC) (600mg orally twice daily), along with hydration, prevents contrast agent-associated nephrotoxicity (CAN) induced by a low dose of non-ionic, low-osmolality contrast dye. We tested whether a double dose of NAC is more effective to prevent CAN. METHODS AND RESULTS: Two-hundred-twenty-four consecutive patients with chronic renal insufficiency (creatinine level > or =1.5mg/dl and/or creatinine clearance <60ml/min), referred to our institution for coronary and/or peripheral procedures, were randomly assigned to receive 0.45% saline intravenously and NAC at the standard dose (600mg orally twice daily; SD Group; n=110) or at a double dose (1200mg orally twice daily; DD Group; n=114) before and after a non-ionic, low-osmolality contrast dye administration. Increase of at least 0.5mg/dl of the creatinine concentration 48h after the procedure occurred in 12/109 patients (11%) in the SD Group and 4/114 patients (3.5%) in the DD Group (P=0.038; OR=0.29; 95% CI=0.09-0.94). In the subgroup with low (<140ml, or contrast ratio <=1) contrast dose, no significant difference in renal function deterioration occurred between the 2 groups. In the subgroup with high (> or =140ml, or contrast ratio >1) contrast dose, the event was significantly more frequent in the SD Group. Conclusions Double dose of NAC seems to be more effective than the standard dose in preventing CAN, especially with high volumes of non-ionic, low-osmolality contrast agent.     

Effectiveness of theophylline in preventing contrast-induced nephropathy after coronary angiographic procedures

Background: Contrast‐induced nephropathy (CIN) is the third most common cause of hospital acquired acute renal failure and is associated with increased morbidity and mortality. The use of theophylline for prevention of CIN has yielded conflicting results. This study aimed at examining the effectiveness of theophylline in prevention of CIN when added to IV hydration and N‐acetylcysteine (NAC). Methods: Patients with stable serum creatinine and at least moderate risk for CIN according to Mehran's risk score were included in this parallel group, 1:1, single‐blind, randomized controlled trial. All patients received IV hydration (1 mL/kg per hour for 24 hours) and NAC (600 mg bid for 2 days). Patients were randomized to placebo (group P) or theophylline (200 mg in 100 mL 0.9% saline, as IV infusion 30 minutes before contrast medium (CM) administration; group T). Patients underwent standard coronary angiography ± angioplasty. Serum creatinine (SCr) was assessed just before and 72 hours after contrast administration and estimated glomerular filtration rate (eGFR) was calculated. Results: This study included 60 patients with mean SCr 1.44 ± 0.7 mg/dL and eGFR 60.2 ± 29.2 mL/min. Mean SCr among group T was 1.54 ± 0.7 mg/dL with eGFR 58.6 ± 28.6 mL/min, while group P showed mean SCr of 1.34 ± 0.7 mg/dL and eGFR of 61.8 ± 30.1 mL/min. Among group P, 6 (20%) patients developed CIN while none of the patients in group T developed CIN. In comparison to placebo, theophylline significantly decreased SCr (P = 0.0001) and increased eGFR (P = 0.001) at 72 hours. Multivariate regression analysis showed that receiving placebo instead of theophylline, anemia, congestive heart failure, chronic renal impairment, and high‐contrast load are all independent predictors for deteriorating renal function after CM administration. Conclusion: Theophylline seems to be an effective prophylaxis against CIN for moderate‐ and high‐risk patients undergoing coronary angiography or angioplasty. It offers additive protection when added to IV hydration and NAC. (J Interven Cardiol 2012;25:404–410)