Renal replacement therapies in the prevention of contrast-induced acute kidney injury

Abstract

Contrast-associated acute kidney injury (CA-AKI) remains a significant cause of hospital-acquired acute kidney injury, particularly in patients undergoing interventional radiology and cardiology procedures. Despite the implementation of preventive measures, such as intravenous hydration, pharmacologic prophylaxis, and minimization of contrast exposure, CA-AKI continues to be associated with increased morbidity, prolonged hospital stays, elevated mortality rates, and greater healthcare costs. Renal replacement therapies (RRT), including haemodialysis and hemofiltration, have been explored as potential strategies to prevent CA-AKI in high-risk populations. However, the existing evidence is inconclusive. While certain studies report a reduced incidence of CA-AKI with early hemofiltration in select patient groups, others have found no significant advantage over standard hydration protocols. Furthermore, practical concerns, including procedural risks, cost implications, and logistical constraints, limit the routine use of prophylactic RRTs in clinical practice. Current clinical guidelines do not endorse the widespread use of RRTs for CA-AKI prevention, though selective application in very high-risk patients may be considered. Robust, large-scale randomized controlled trials are needed to identify patient subgroups that might derive benefit from this intervention. In the interim, optimized hydration and contrast minimization remain the cornerstone strategies for CA-AKI prevention.

Key Words: Contrast-associated acute kidney injury; Renal replacement therapy; Hemodialysis; Hemofiltration; Prevention

Core Tip: Contrast-associated acute kidney injury remains a major complication in high-risk patients undergoing contrast-based procedures. While standard prevention relies on individualized hydration and contrast minimization, the role of prophylactic renal replacement therapy remains controversial. Evidence consistently shows that hemodialysis does not prevent contrast-associated acute kidney injury, whereas early hemofiltration may offer benefit in carefully selected patients with advanced chronic kidney disease and limited tolerance to fluid expansion. However, inconsistent trial results and logistical constraints preclude routine use. This review critically evaluates current evidence, highlights patient selection and timing considerations, and underscores the need for adequately powered randomized trials.

INTRODUCTION

The administration of iodinated contrast media remains indispensable for modern diagnostic imaging and interventional procedures, including computed tomography, coronary angiography, and percutaneous coronary interventions (PCI)[1]. However, contrast exposure is associated with the risk of acute kidney injury (AKI), which carries significant short- and long-term morbidity, prolonged hospitalizations, and increased healthcare costs[1-6]. Precise terminology is critical: Contrast-associated AKI (CA-AKI) refers to any AKI temporally occurring after contrast exposure without implying causality, whereas contrast-induced AKI should be applied only when a direct causal relationship between contrast and renal injury is established[1]. This distinction is particularly relevant for intravenous contrast-enhanced computed tomography, where serum creatinine fluctuations may reflect underlying comorbidities, hemodynamic instability, or concomitant nephrotoxic agents rather than direct contrast toxicity.

Diagnostic criteria for CA/contrast-induced AKI are heterogeneous. Traditionally, a serum creatinine increase of ≥ 0.5 mg/dL within 48-72 hours post-contrast has been used[2,3], but contemporary studies increasingly adopt Kidney Disease: Improving Global Outcomes definitions, which incorporate both absolute and relative changes in creatinine, as well as urine output[1]. Accurate baseline renal function assessment and post-procedural monitoring are essential, particularly in high-risk populations, with repeat measurements recommended at 48-72 hours and additional follow-up if clinical deterioration occurs. This narrative review aims to critically evaluate the current evidence regarding the role of renal replacement therapies (RRT) in the prevention of CA-AKI, with particular emphasis on patient selection, timing, and clinical outcomes. The review was based on a structured literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases, focusing on studies evaluating RRT for the prevention of CA-AKI from January 2000 to January 2026. Priority was given to randomized controlled trials, meta-analyses, and major society guidelines, with additional landmark studies included where clinically relevant.

MAJOR RISK FACTORS FOR CA-AKI

The risk of CA-AKI is influenced by patient-, procedure-, and contrast-specific factors. Chronic kidney disease (CKD) remains the most significant predisposing condition, particularly in advanced stages (estimated glomerular filtration rate < 30 mL/minute/1.73 m²)[7-11]. Other patient-related risk factors include diabetes mellitus, heart failure, hypotension, hypovolemia, multiple myeloma, anemia, and advanced age[1,7-11]. The presence of multiple risk factors has a synergistic effect on CA-AKI susceptibility, resulting in incidence rates of 10%-30% in high-risk patients undergoing coronary angiography or PCI[1]. By contrast, the risk is negligible in patients with normal renal function and no comorbidities.

Procedure-related factors also influence risk. Intra-arterial administration is associated with higher CA-AKI rates compared with intravenous routes, likely due to increased renal exposure and hemodynamic perturbations[1,8-10]. Total contrast volume and procedural complexity are directly correlated with AKI risk, while the type of contrast agent-low-osmolal vs iso-osmolal further modulates nephrotoxicity[12]. Even minimal contrast volumes may precipitate AKI in extremely vulnerable patients, such as those with advanced CKD and diabetes, highlighting the importance of individualized risk assessment and careful procedural planning[11].

PATHOPHYSIOLOGY AND CLINICAL FEATURES

The pathophysiology of CA-AKI is multifactorial and incompletely understood. Key mechanisms include renal vasoconstriction, medullary hypoxia, and direct tubular epithelial injury, resulting in acute tubular necrosis[1-3]. Contrast agents may exert both osmotic and chemotoxic effects, with some studies suggesting agent-specific nephrotoxicity mediated by oxidative stress, mitochondrial dysfunction, and apoptosis in tubular cells[1,3]. Hemodynamic instability, pre-existing CKD, and comorbid conditions exacerbate susceptibility, creating a “perfect storm” for renal injury in high-risk patients[1]. While a dose-dependent effect is evident during coronary angiography, routine intravenous contrast rarely demonstrates a clear dose-response relationship[1].

Clinically, CA-AKI is usually non-oliguric, characterized by a rise in serum creatinine ≥ 0.5 mg/dL within 24-48 hours post-contrast, which generally resolves within 3-7 days[2,3]. Despite its often transient nature, CA-AKI is independently associated with increased early and late mortality, progression of CKD, and heightened risk of cardiovascular events[4-6]. These associations underscore the critical importance of identifying high-risk patients and implementing effective preventive strategies (Table 1).

Table 1 Major randomized controlled trials and meta-analyses on hemodialysis and hemofiltration for contrast-associated acute kidney injury prevention.

Ref.	Publication year	Population	Intervention	Comparison	Outcome	Key finding
Sterner et al[20]	2000	Patients with moderately reduced renal function	Hemodialysis	Standard of care	Contrast-associated acute kidney injury	Reduction of contrast media in plasma but no reduction in CA-AKI
Vogt et al[21]	2001	Patients with baseline serum creatinine levels > 2.3 mg/dL	Hemodialysis	Non-hemodialysis	Renal function, hemodialysis requirement, and relevant clinical events	Hemodialysis in all patients with reduced renal function did not improve the rate of CA-AKI
Lehnert et al[22]	1998	Patients with reduced renal function (creatinine 24 mg/dL) undergoing angiography	Hemodialysis for 3 hours as soon as possible after administration of contrast medium	Standard of care	Serum concentrations of contrast medium and creatinine	Hemodialysis eliminates contrast medium effectively. No influence on CA-AKI
Marenzi et al[25]	2006	Patients with chronic kidney disease undergoing percutaneous coronary intervention	Hemofiltration before and after contrast administration	Standard medical care	Contrast-associated acute kidney injury; in-hospital mortality	Contrast-associated acute kidney injury: 3% vs 26%; lower in-hospital mortality in hemofiltration group
Marenzi et al[24]	2003	Patients with chronic kidney disease undergoing percutaneous coronary intervention	Hemofiltration after contrast administration only	Standard medical care	Contrast-associated acute kidney injury	Contrast-associated acute kidney injury: 26% vs 50% in control group
Cruz et al[2]	2012	Meta-analysis on the use of renal replacement therapies for the prevention of CA-AKI	Renal replacement therapies	-	Contrast-associated acute kidney injury	Periprocedural RRT did not decrease the incidence. Hemodialysis increases CA-AKI
Brar et al[17]	2014	High-risk patients undergoing percutaneous coronary intervention - POSEIDON trial	Left ventricular end-diastolic pressure-guided hydration	Standard intravenous hydration	Contrast-associated acute kidney injury	Tailored, hemodynamically guided hydration reduced contrast-associated acute kidney injury incidence
Nijssen et al[15]	2017	Patients with chronic kidney disease undergoing elective procedures - AMACING trial	Standard intravenous hydration	No intravenous hydration	Contrast-associated acute kidney injury; fluid-related adverse events	Increased fluid-related adverse events in low-risk patients receiving routine hydration

CA-AKI: Contrast-associated acute kidney injury; RRT: Renal replacement therapies.

PREVENTIVE STRATEGIES

Risk stratification

Several tools have been developed to quantify CA-AKI risk and guide prophylaxis. In interventional cardiology, the Mehran risk score combines baseline renal function, hemodynamic variables, comorbidities, and procedural characteristics to predict the probability of post-procedural AKI[7]. Identifying high-risk patients, including those with estimated glomerular filtration rate < 30 mL/minute/1.73 m², shock, anemia, and left ventricular dysfunction, allows for targeted preventive interventions[7-11].

Procedural and contrast minimization strategies

Minimizing contrast exposure remains a cornerstone of CA-AKI prevention. Techniques include limiting contrast volume, avoiding unnecessary injections, using low-contrast protocols, and leveraging physiological assessment of stenoses rather than angiographic guidance alone[1,8-10]. Even very small contrast doses (as low as 20 mL) may precipitate AKI in patients with advanced CKD and diabetes, emphasizing the need for individualized procedural planning[11].

Contrast media selection

Low-osmolal contrast media reduce CA-AKI incidence compared with high-osmolal agents, while iso-osmolal agents offer modest additional protection[12]. Selection of the least nephrotoxic agent, particularly in high-risk patients, should be considered as part of a multifaceted preventive approach.

Hydration: Intravenous isotonic saline is the most widely accepted preventive intervention. Periprocedural hydration enhances renal perfusion, dilutes nephrotoxic contrast, and may mitigate oxidative stress[13-16]. The POSEIDON trial demonstrated that fluid replacement guided by left ventricular end-diastolic pressure significantly reduced CA-AKI incidence and improved hemodynamic stability[17]. However, indiscriminate volume loading carries risks, as highlighted by the AMACING trial, which reported increased fluid-related complications in patients receiving standardized hydration[15]. This underscores the importance of individualized hydration strategies, balancing renal protection with fluid overload risk.

Pharmacologic interventions

Despite extensive research, pharmacologic agents such as N-acetylcysteine have demonstrated inconsistent efficacy in preventing CA-AKI. Meta-analyses and randomized trials have failed to establish robust clinical benefit, and pharmacologic prophylaxis is generally recommended only as adjunctive therapy in select high-risk populations[18].

RRT IN CA-AKI PREVENTION

Hemodialysis

While hemodialysis (HD) efficiently clears contrast agents from circulation[19], multiple randomized trials have failed to demonstrate any reduction in CA-AKI incidence or improvement in clinical outcomes in patients with severe CKD[20-22]. HD itself may exacerbate renal injury through hemodynamic instability, ultrafiltration-induced hypovolemia, and activation of inflammatory pathways[23]. Furthermore, renal injury occurs immediately after contrast exposure, whereas HD in these studies was often initiated after a significant delay, limiting its potential preventive effect.

Hemofiltration

Hemofiltration (HF) allows continuous solute and fluid removal with greater hemodynamic stability than HD. Evidence suggests that HF initiated before and during contrast exposure may reduce CA-AKI incidence and improve both in-hospital and 1-year survival in high-risk patients[24,25]. Timing appears critical; prophylactic HF before and after contrast administration is significantly more effective than post-procedural HF alone[25]. Interestingly, some authors suggest that simultaneous HF could provide better renal protection compared to periprocedural HF[26]. The 2018 European Society of Cardiology/European Association for Cardio-Thoracic Surgery myocardial revascularization guidelines recommend considering prophylactic HF 6 hours before complex PCI in high-risk patients (class IIb, level B)[27]. Despite these promising findings, meta-analyses and Kidney Disease: Improving Global Outcomes guidelines do not endorse routine RRT due to inconsistent evidence, logistical challenges, and resource constraints[1,2]. Therefore, prophylactic HF should be regarded as a niche strategy, reserved for patients with severe CKD (stage IV), particularly those with concomitant cardiac dysfunction in whom fluid administration is limited or contraindicated.

FUTURE DIRECTIONS AND CLINICAL IMPLICATIONS

Although HD is ineffective for CA-AKI prevention, HF may provide benefit in carefully selected high-risk populations. Early initiation, controlled volume expansion, and hemodynamic stabilization appear to be the main mechanisms of benefit rather than extracorporeal contrast clearance itself[28]. Guidelines and meta-analysis advise that kidney replacement therapy should neither be started nor have its timing modified solely due to the administration of contrast agents[27,29-31]. Future randomized trials with sufficient power are needed to refine patient selection, optimize timing, and determine the most effective RRT modality. In the meantime, prevention should focus on personalized hydration protocols, risk stratification, minimization of contrast exposure, and optimization of comorbid conditions.

CONCLUSION

CA-AKI remains a clinically significant complication of contrast administration, particularly in high-risk patients. Available evidence indicates that contrast removal alone via HD does not prevent CA-AKI, while HF may offer benefits when applied early in selected populations. Current guidelines do not support standard prophylactic RRT, emphasizing that prevention should rely on hydration, careful risk assessment, and contrast minimization. Further large-scale, randomized studies are needed to define patient subgroups that may derive meaningful benefit from prophylactic RRT and to establish evidence-based protocols for its application.