Periprocedural Hydration Research Articles

The incidence of contrast-induced nephropathy (CIN) following transarterial chemoembolisation (TACE) in patients with hepatocellular carcinoma (HCC)

The purpose of this retrospective study was to investigate the incidence of contrast-induced nephropathy (CIN) caused by transarterial chemoembolisation (TACE) in patients with hepatocellular carcinoma (HCC). One hundred forty-one patients treated between 2005 and 2008 undergoing 305 consecutive sessions of TACE were enrolled. CIN was defined as an increase in the serum creatinine level of more than 0.5 mg/dl or more than 25 % from baseline within 3 days after TACE without any other identifiable cause of acute kidney injury. CIN by the present definition was observed after 2.6 % of the TACE sessions. No patient showed clinical signs or symptoms of acute renal failure, or required haemodialysis. None of the patients with an estimated glomerular filtration rate of <60 ml/min/1.73 m(2) developed CIN. The present study suggests that TACE is a relatively safe procedure in terms of the risk of CIN under vigorous periprocedural hydration and that the incidence of CIN is comparable to that of AKI associated with intravenous CM administration. • CIN would be lower for non-coronary arterial intervention than for coronary intervention. • The present study suggests that the CIN rates following TACE are low. • The incidence of CIN is comparable to that after intravenous CM administration.

Aggressive Hydration With Lactated Ringer's Solution Reduces Pancreatitis After Endoscopic Retrograde Cholangiopancreatography

Pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP). We performed a pilot study to determine whether aggressive periprocedural hydration with lactated Ringer's solution reduces the incidence of pancreatitis after ERCP. Patients who underwent first-time ERCP were randomly assigned to groups (2:1) that received aggressive hydration with lactated Ringer's solution (3 mL/kg/h during the procedure, a 20-mL/kg bolus after the procedure, and 3 mL/kg/h for 8 hours after the procedure, n = 39) or standard hydration with the same solution (1.5 mL/kg/h during and for 8 hours after procedure, n = 23). Serum levels of amylase, visual analogue pain scores (scale of 0-10), and volume overload were assessed at baseline and 2, 8, and 24 hours after ERCP. The primary end point, post-ERCP pancreatitis, was defined as hyperamylasemia (level of amylase >3 times the upper limit of normal) and increased epigastric pain (≥3 points on visual analogue scale) persisting for ≥24 hours after the procedure. Secondary end points included hyperamylasemia, increased pain, and volume overload. None of the patients who received aggressive hydration developed post-ERCP pancreatitis, compared with 17% of patients who received standard hydration (P = .016). Hyperamylasemia developed in 23% of patients who received aggressive hydration vs 39% of those who received standard hydration (P = .116, nonsignificant); increased epigastric pain developed in 8% of patients who received aggressive hydration vs 22% of those who received standard hydration (P = .146, nonsignificant). No patients had evidence of volume overload. On the basis of a pilot study, aggressive intravenous hydration with lactated Ringer's solution appears to reduce the development of post-ERCP pancreatitis and is not associated with volume overload. ClinicalTrials.gov, Number: NCT 01758549.

Ascorbic Acid for the Prevention of Contrast‐Induced Nephropathy After Coronary Angiography in Patients With Chronic Renal Impairment: A Randomized Controlled Trial

To determine the incidence of contrast-induced nephropathy (CIN) and to assess the effectiveness of ascorbic acid in the prevention of CIN after coronary angiography in patients with chronic renal impairment. CIN is the third most common cause of hospital-acquired renal failure. It is well documented that periprocedural hydration is effective in the prevention of CIN. Little data exist on the effectiveness of ascorbic acid, a vitamin with antioxidative action. Patients with stable serum creatinine level >107 μmol/L (n = 81) undergoing coronary angiography were randomized to receive either ascorbic acid (N = 40) or placebo (N = 41) before the procedure. All patients received intravenous volume expansion with normal saline before the procedure. CIN was defined as an increase of serum creatinine level >25% from baseline measured 3 to 4 days after the procedure. CIN occurred totally in 5/81 patients (6.2%); in two patients (3%) in the ascorbic acid group and in three patients (7.3%) in the placebo group (P = 0.512). Postprocedural worsening of renal function (postprocedural increase of serum creatinine level) was present in 10/81 patients (12.3%) in the ascorbic acid group and in 19/81 patients (23.4%) in the placebo group (P = 0.038). No patient required dialysis treatment. We found no statistically significant impact of ascorbic acid on the incidence of CIN in patients with chronic renal impairment undergoing coronary arteriography or angioplasty. Ascorbic acid may still have some protective role in CIN reflected in lower incidence of worsening of renal function in the treated group.

N-acetylcysteine for Prevention of Contrast-Induced Nephropathy: A Narrative Review

Contrast-induced nephropathy (CIN) affects in-hospital, short- and long-term morbidity and mortality. It also leads to prolonged hospital stay and increased medical cost. Given the potential clinical severity of CIN, there has been considerable interest in the development of preventative strategies to reduce the risk of contrast-induced renal deterioration in at-risk populations. A number of pharmacologic and mechanical preventive measures have been attempted, but no method other than adequate periprocedural hydration has been conclusively successful. Since its introduction in 2000, N-acetylcysteine (NAC) has been widely investigated, albeit with conflicting findings for its nephroprotection capability in patients receiving contrast media procedures. However, there is still virtually no definitive evidence of effectiveness of NAC. Although the exact mechanism responsible for the protective action of NAC from renal function deterioration remains unclear, the antioxidant and vasodilatory properties of NAC have been suggested as the main mechanisms. This review summarizes the current status of NAC as a potential agent to prevent renal functional deterioration and its limitations.

Prevention of contrast-induced acute kidney injury by theophylline in elderly patients with chronic kidney disease

Although the optimal strategy for preventing contrast-induced acute kidney injury (CI-AKI) has not yet been established, the current strategy focuses on adequate periprocedural hydration, the use of a low amount of low or iso-osmolar contrast medium, and the application of adjunctive therapies, including hemofiltration, hemodialysis and drugs. Previous trials and meta-analyses concerning the use of the adenosine antagonist theophylline have revealed contradictory results. We sought to evaluate the effect of theophylline in CI-AKI prevention in well-hydrated elderly patients with chronic kidney disease. We therefore conducted a randomized, double-blind, placebo-controlled trial involving 56 patients who had been referred for cardiac coronary angiography and/or angioplasty. 31 of these patients were randomly assigned to 200 mg theophylline IV before the procedure, and 25 to a placebo. The iso-osmolar contrast medium iodixanol was used. The primary endpoint was an increase in serum creatinine at study termination 48 h after contrast medium administration. Baseline characteristics in the placebo and theophylline groups were similar in terms of median age (75 years), estimated glomerular filtration rate (33 ± 10 vs. 33 ± 10 ml/min/1.73 m²; p = 0.87), diabetes mellitus (80 vs. 71%; p = 0.54), and amount of contrast used (94 ± 35 vs. 95 ± 38 ml; p = 0.89). There was no difference in serum creatinine at baseline (2.06 ± 0.59 vs. 2.02 ± 0.45 mg/dl; p = 0.62) or study termination (2.06 ± 0.68 vs. 2.10 ± 0.53; p = 0.79). A prophylactic effect of theophylline was not observed. The incidence of renal impairment following exposure to the contrast medium was low. This fact can be attributed to adequate parenteral hydratation and the use of the minimum amount of contrast medium necessary.

Predictors for contrast media-induced nephropathy and long-term survival: Prospectively assessed data from the randomized controlled Dialysis-Versus-Diuresis (DVD) trial

Among the numerous studies concerning contrast media-induced nephropathy (CIN), there was no prospective trial that provided data on the long-term outcomes. To prospectively assess predictors of CIN and long-term outcomes of affected patients. Four hundred twelve consecutive patients with serum creatinine levels of 115 micromol/L to 309 micromol/L (1.3 mg/dL to 3.5 mg/dL) undergoing elective coronary angiography were included. Patients were randomly assigned to periprocedural hydration alone, hydration plus one-time hemodialysis or hydration plus N-acetylcysteine. Multivariate logistic regression identified the following as predictors of CIN within 72 h (equivalent to an increase in creatinine 44.2 micromol/L [0.5 mg/dL] or more) : prophylactic postprocedural hemodialysis (OR 2.86, 95% CI 1.07 to 7.69), use of angiotensin-converting enzyme inhibitors (OR 6.16, 95% CI 2.01 to 18.93), baseline glomerular filtration rate (OR 0.94, 95% CI 0.90 to 0.98) and the amount of contrast media given (OR 1.01, 95% CI 1.00 to 1.01). With regard to long-term outcome (mean follow-up 649 days), multivariate Cox regression models found elevated creatinine levels at 30 days (hazard rate ratio [HRR] 5.48, 95% CI 2.85 to 10.53), but not CIN within 72 h (HRR 1.12, 95% CI 0.63 to 2.02), to be associated with increased mortality. In addition, independent predictors for death during follow-up included left ventricular ejection fraction lower than 35% (HRR 4.01, 95% CI 2.22 to 7.26), serum phosphate (HRR 1.64, 95% CI 1.10 to 2.43) and hemoglobin (HRR 0.80, 95% CI 0.67 to 0.96). From the present prospective trial, performance of postprocedural hemodialysis, use of angiotensin-converting enzyme inhibitors, reduced baseline glomerular filtration rate and amount of contrast media were independent predictors of CIN within 72 h after catheterization. Assessing renal function after 30 days, rather than within 72 h, seemed to be more predictive for patients' long-term survival.

Cystatin C and contrast-induced nephropathy

Sir, The paper by Kimmel et al. [1] concludes that cystatin C blood level variations are a more reliable parameter than serum creatinine increments for the diagnosis of contrastinduced nephropathy (CIN). However, this conclusion does not seem sufficiently supported by the data to us. Since the definition of CIN is based on serum creatinine variations, it is not clear what the meaning is of the cystatin C increase when the former does not occur. Does it reflect a true GFR reduction or some other condition, i.e. the release of cystatin C from atherosclerotic vascular lesions during arterial catheterization [2] or the biological variability of the parameter [3]? We are also puzzled with the variability of cystatin C in the period d-1/d0. Looking at Figure 1, our feeling is that it is quite large. As a matter of fact, it was reported that the critical difference for sequential values is 37% for serum cystatin C—a value that includes the cystatin C levels plotted in Figure 1—and only 14% for serum creatinine [3]. The authors state that the temporary increase in GFR possibly due to the peri-procedural hydration does not translate into a cystatin C decrement because of its slower kinetics vis-a-vis serum creatinine. However, what is the evidence for such a statement? Is it just speculation to explain the dichotomic trends between serum cystatin C and creatinine levels? The issue is very important, since if cystatin C really has a delayed progression with respect to serum creatinine, we might suspect that the interval d0/d2, 48 h, is too long to grasp mild, transient serum creatinine variations occurring inbetween. We think that, although cystatin C is an attractive biomarker of GFR, before concluding that it should be the preferred biomarker for the development of CIN, an experimental design with a more strict timing in sampling and a much larger case population is necessary.

Contrast‐induced nephropathy

Contrast induced nephropathy (CIN) is an iatrogenic disorder, resulting from exposure to contrast media. Contrast-induced hemodynamic and direct cytotoxic effects on renal structures are highly evident in its pathogenesis, whereas other mechanisms are still poorly understood. CIN is typically defined as an increase in serum creatinine by either > or =0.5 mg/dl or by > or =25% from baseline within the first 2-3 days after contrast administration. Although rare in the general population, CIN has a high incidence in patients with an underlying renal disorder, in diabetics, and the elderly. The risk factors are synergistic in their ability to produce CIN. The best way to prevent CIN is to identify the patients at risk and to provide adequate peri-procedural hydration. The role of various drugs in prevention of CIN is still controversial and warrants future studies. Despite remaining uncertainty regarding the degree of nephrotoxicity produced by various contrast agents, in current practice non-ionic low-osmolar contrast media are preferred over the high-osmolar contrast media in patients with renal impairment.

Prevention of contrast-induced nephropathy: a critical review

Although contrast-induced nephropathy (CIN) is common and portends a significant morbidity and mortality, only few large and well designed trials have assessed the available prophylactic measures and there are no clear evidence-based guidelines that can easily be adopted by the clinician. We critically discuss the evidence for periprocedural hydration, pharmacological agents, periprocedural withdrawal of medication, application of renal replacement therapy and the use of contrast media. Pending confirmation of the superiority of sodium bicarbonate, NaCl 0.9% remains the fluid of choice for periprocedural hydration. A recent trial found a dose-dependent beneficial effect of acetylcysteine on CIN and mortality, adding to the controversy on the prophylactic use of this agent. Publication bias of acetylcysteine trials may have confounded the results of the meta-analyses, since negative results were more likely to be published as an abstract only. Periprocedural haemofiltration protected against CIN in a high-risk population, but the results require confirmation before the technique can be recommended. Pending randomized controlled trials with rigorous scientific design, we propose practical mixed evidence-based and opinion-based guidelines for the prevention of CIN, using a stratification of patients into three risk groups, based on their renal function and a risk-prediction model.

Role of Apoptosis in the Pathogenesis of Contrast Media-induced Nephropathy and Hints for its Possible Prevention by Drug Treatment

Contrast-induced nephropathy (CIN) is a worrying concern in at-risk patients. Its pathophysiological mechanism remains speculative and is possibly modulated according to the risk factor(s) and clinical presentation of the patients. Overall, iodinated contrast media (CM) have been shown, in animal models, to induce medullary hypoxia. Furthermore, numerous studies have demonstrated that they have a direct cytotoxic potential on proximal (LLC-PK1) as well as distal (MDCK) tubular cell lines and mesangial cells. A pro-apoptotic potential of such molecules has been found on various cell types including renal tubular and mesangial cells, both in vitro and in vivo. This pro-apoptotic effect on tubular cells has been found to be concentration- and time-dependent. In addition to periprocedural hydration, which is the cornerstone of CIN, several drugs have been investigated for the pharmacological prophylaxis of CIN, either on pre-clinical models or in clinical studies. Some of them (theophylline, Nacetylcysteine, the prostacyclin analogue beraprost or taurine) are known to interfere with the apoptosis pathways. This article reviews and critically discusses the available data concerning the role of apoptosis in the mechanism of CIN and its pharmacological prophylaxis. It also reviews the putative interaction of gadolinium chelates, used as CM for magnetic resonance imaging, with apoptosis pathways.

Contrast-Induced Nephropathy

Contrast medium–induced nephropathy (CIN) is a common cause of acute renal dysfunction. During the past few years, several publications have provided clinical and experimental data on this topic. Our review focuses on 4 major concerns of CIN relevant in clinical practice: (1) What is the evidence that CIN is a clinically relevant and a dangerous condition for the patient? (2) Is there a difference in CIN rate among different contrast media, and how is that related to the physicochemical properties of different available contrast media? (3) What is the evidence that periprocedural hydration is an effective, appropriate, and safe method to prevent CIN? (4) What is the evidence for the use of a drug, in particular acetylcysteine, to prevent CIN? CIN has gained increased attention in the clinical setting, particularly during cardiac intervention but also in many other radiological procedures in which iodinated contrast media are used. There is at present good clinical evidence from well-controlled randomized studies that CIN is a common cause of acute renal dysfunction.1,2 CIN is the acute deterioration of renal function after parenteral administration of radiocontrast media in the absence of other causes. CIN is generally defined as an increase in serum creatinine concentration of >0.5 mg/dL (>44 μmol/L) or 25% above baseline within 48 hours after contrast administration.3–7 Although the exact mechanisms of CIN have yet to be fully elucidated, several causes have been described. Increased adenosine-, endothelin-, and free radical–induced vasoconstriction and reduced nitric oxide– and prostaglandin-induced vasodilatation have been observed. These mechanisms cause ischemia in the deeper portion of the outer medulla, an area with high oxygen requirements and remote from the vasa recta supplying the renal medulla with blood. Contrast agents also have direct toxic effects on renal tubular cells, causing vacuolization, altered mitochondrial function, and apoptosis.8 Atopy …

Recent advances in the prevention of radiocontrast-induced nephropathy

Radiocontrast nephropathy is a serious clinical problem associated with increased morbidity and mortality, particularly in patients with chronic renal failure. The optimal strategy to prevent radiocontrast nephropathy has not been established. This article reviews recent clinical researches concerning new developments in the prevention of radiocontrast nephropathy and analyzes unresolved issues. Among all prophylactic measures that have been proposed, periprocedural hydration with isotonic saline has demonstrated effectiveness in the prevention of radiocontrast nephropathy. Thus, it remains the most frequently applied measure in clinical practice. Recently, additional benefit has been shown to derive from the infusion of isotonic alkalizing (sodium bicarbonate), instead of isotonic (sodium chloride) solutions. The use of nonionic low-osmolar and, more recently, nonionic iso-osmolar contrast agents has been demonstrated to significantly reduce the risk of radiocontrast nephropathy in patients with renal impairment, in comparison with hyperosmolar contrast media. Recently, periprocedural hemofiltration has emerged as a safe and very effective strategy to prevent radiocontrast nephropathy and to reduce its associated poor outcome in patients with severe chronic renal failure. In the past few years, several trials with acetylcysteine have shown conflicting results. Nevertheless, most of them indicated that acetylcysteine, particularly when associated with adequate hydration, might be useful in preventing radiocontrast nephropathy in patients with renal impairment. A possible dose-dependent protective effect has been suggested by more recent trials that included patients undergoing coronary interventional procedures requiring large contrast volume. Adequate prophylaxis is needed to reduce the high morbidity and mortality associated with radiocontrast nephropathy in high-risk patients. By reviewing the available evidence from clinical trials, this article provides an overview of current strategies and unresolved issues concerning the prevention of radiocontrast nephropathy.

Prevention of Contrast Nephropathy in Critically Ill Patients Using Acetylcysteine and Theophylline

Compared with periprocedural hydration alone, acetylcysteine with hydration significantly reduces the risk of contrast nephropathy in patients with chronic renal insufficiency by 50%. For elective contrast procedures, acetylcysteine should be given in a dose of 600 mg twice daily the day before and on the procedure day. For emergency procedures, a high dose intravenous regimen (150 mg/kg in 500 mL normal saline over 30 minutes immediately before contrast followed by 50 mg/kg in 500 mL normal saline over 4h) is effective. Given the low cost and good side-effect profile of acetylcysteine, it would seem prudent to give this drug with intravenous fluids to all critically ill patients scheduled for intravenous or intraarterial contrast procedures. Theophylline in a dose of 200 mg or 2.5 mg/kg i.v. 30 minutes before contrast may be an effective alternative for emergency procedures. Although its benefit compared with periprocedural hydration alone seems less well established, theophylline is a particularly attractive option for emergency procedures.

Análisis crítico de un artículo: Acetilcisteína para prevenir falla renal por medio de contraste Birck R, Krzossok S, Markowetz F, Schnulle P, van der Woude FJ, Braun C. Acetylcysteine for prevention of contrast nephropathy: meta-analysis. Lancet 2003; 362 (9384): 598-603

Background: Contrast nephropathy is associated with increased in hospital morbidity and mortality and leads to extension of hospital stay in patients with chronic renal insufficiency. Acetylcysteine seems to be a safe and inexpensive way to reduce contrast nephropathy. We aimed to assess the efficacy of acetylcysteine to prevent contrast nephropathy after administration of radiocontrast media in patients with chronic renal insufficiency. Methods: We did a meta-analysis of randomized controlled trials comparing acetylcysteine and hydration with hydration alone for preventing contrast nephropathy in patients with chronic renal insufficiency. The trials were identified through a combined search of the BIOSIS+/RRM, MEDLINE, Web of Science, Current Contents Medizin, and The Cochrane Library Databases. We used incidence of contrast nephropathy 48 h after administration of radiocontrast media as an outcome measure. Findings: Seven trials including 805 patients were eligible according to our inclusion criteria and were analyzed. Overall incidence of contrast nephropathy varied between 8% and 28%. Since significant heterogeneity was indicated by the Q statistics (p=0.016) we used a random effects model to combine the data. Compared with periprocedural hydration alone, administration of acetylcysteine and hydration significantly reduced the relative risk of contrast nephropathy by 56% (0.435 [95% CI 0.215-0.879], p=0.02) in patients with chronic renal insufficiency. Meta-regression revealed no significant relation between the relative risk of contrast nephropathy and the volume of radiocontrast media administered or the degree of chronic renal insufficiency before the procedure. Interpretation: Compared with periprocedural hydration alone, acetylcysteine with hydration significantly reduces the risk of contrast nephropathy in patients with chronic renal insufficiency. The relative risk of contrast nephropathy was not related to the amount of radiocontrast media given or to the degree of chronic renal insufficiency before the procedure

Acetylcysteine for prevention of contrast nephropathy: meta-analysis

Contrast nephropathy is associated with increased in-hospital morbidity and mortality and leads to extension of hospital stay in patients with chronic renal insufficiency. Acetylcysteine seems to be a safe and inexpensive way to reduce contrast nephropathy. We aimed to assess the efficacy of acetylcysteine to prevent contrast nephropathy after administration of radiocontrast media in patients with chronic renal insufficiency. We did a meta-analysis of randomised controlled trials comparing acetylcysteine and hydration with hydration alone for preventing contrast nephropathy in patients with chronic renal insufficiency. The trials were identified through a combined search of the BIOSIS+/RRM, MEDLINE, Web of Science, Current Contents Medizin, and The Cochrane Library Databases. We used incidence of contrast nephropathy 48 h after administration of radiocontrast media as an outcome measure. Seven trials including 805 patients were eligible according to our inclusion criteria and were analysed. Overall incidence of contrast nephropathy varied between 8% and 28%. Since significant heterogeneity was indicated by the Q statistics (p=0.016) we used a random-effects model to combine the data. Compared with periprocedural hydration alone, administration of acetylcysteine and hydration significantly reduced the relative risk of contrast nephropathy by 56% (0.435 [95% CI 0.215-0.879], p=0.02) in patients with chronic renal insufficiency. Meta-regression revealed no significant relation between the relative risk of contrast nephropathy and the volume of radiocontrast media administered or the degree of chronic renal insufficiency before the procedure. Compared with periprocedural hydration alone, acetylcysteine with hydration significantly reduces the risk of contrast nephropathy in patients with chronic renal insufficiency. The relative risk of contrast nephropathy was not related to the amount of radiocontrast media given or to the degree of chronic renal insufficiency before the procedure.

Contrast agent-associated nephrotoxicity

Radiocontrast media can lead to a reversible form of acute renal failure that begins soon after the contrast dye administration and generally is benign. Contrast media accounts for 10% of all causes of hospital-acquired acute renal failure and represents the third leading cause of in-hospital renal function deterioration after decreased renal perfusion and postoperative renal insufficiency. The in-hospital mortality rate in patients developing renal insufficiency is related directly to the magnitude increase of serum creatinine concentration. The mortality rate ranges from 3.8% with an increase in serum creatinine level of 0.5 to 0.9 mg/dL to 64% with an increase of greater than 3.0 mg/dL. The mechanism by which contrast-induced renal failure occurs is not well understood. Contrast agent-associated nephrotoxicity appears to be a result of direct contrast-induced renal tubular epithelial cell toxicity and renal medullary ischemia. Furthermore, a key mechanism seems to be alteration in renal dynamics, probably caused by imbalances between vasodilator and vasoconstrictor factors, including the activities of nitric oxide, prostaglandins, endothelin, and reactive oxygen species. The optimal strategy to prevent contrast-associated nephrotoxicity remains uncertain. At present, recommendations are as follows: (1) periprocedural hydration, (2) use of a low-osmolality contrast, and (3) limiting the amount of contrast agent. Recently, considerable interest has resulted from the preliminary positive data on the effectiveness of prophylactic administration of acetylcysteine and fenoldopam. The former may prevent the direct oxidative tissue damage, whereas the latter is a selective intrarenal vasodilator. Copyright 2003, Elsevier Science (USA). All rights reserved.