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Less than 1% of patients with CIN ultimately go on to require dialysis, the number being slightly higher in patients with underlying renal impairment (3.1%) and in those undergoing primary PCI for MI (3%). However, in patients with diabetes and severe renal failure, the rate of dialysis can be as high as 12%. Patients who get dialyzed do considerably worse, with inhospital mortality rates of 35.7% (compared with 7.1% in the nondialysis group) and a 2-year survival rate of only 19%.

CM have molecular weights that range between 650 and 1600 mOsm/kg. They have low lipophilicity, low plasma protein binding, and minimal biotransformation. They quickly equilibrate across capillary membranes and have volumes of distribution equivalent to that of the extracellular fluid volume. In patients with normal renal function, CM are excreted with the first glomerular passage and the decrease in their plasma concentration follows a 2-part exponential function, a distribution phase and an elimination phase. However, in patients with renal impairment, the renal clearance values are reduced. For example, 50% of the low-osmolarity contrast agent iomeprol is eliminated within 2 hours in healthy subjects, compared with 16-84 hours in patients with severe renal impairment.

In patients already on dialysis, the commonly sited issues with contrast administration include volume load and direct toxicity of contrast to the remaining nonfunctional nephrons and nonrenal tissues. Thus, the perceived need for emergent dialysis and contrast removal.

Rodby attempted to address these concerns, calculating that the administration of 100 mL of hyperosmolar contrast would move 265 mL of water from the intracellular to the extracellular compartment, resulting in an increase in extracellular volume by 365 mL. The increase in intravascular space would therefore be only a third, or 120 mL. Fluid shifts with LOCM are even less. He also found that extrarenal toxicity of CM was cited in mostly single case reports, and no objective evidence could be identified in 3 prospective studies.^[31]

The risk of acute damage from contrast is therefore greatest in patients with CKD. This can be explained by the increase in single nephron GFR and, thus, the filtered load of contrast per nephron. This is akin to a double hit to the remaining nephrons; increased contrast load and prolonged tubular exposure. While this may not seem to be a concern in patients with ESRD who are already on dialysis, residual renal function, in fact, plays a big role in their outcome, more so in patients on peritoneal dialysis. Its preservation is therefore important.^[31]

CM can be effectively and efficiently removed by hemodialysis (HD). Factors that influence CM removal include blood flow, membrane surface area, molecular size, transmembrane pressure, and dialysis time. High-flux dialysis membranes with blood flows of between 120-200 mL/min can remove almost 50% of iodinated CM within an hour and 80% in 4 hours. Even in patients with CKD, in whom contrast excretion is delayed, it was found that 70-80% of contrast can be removed by a 4-hour HD treatment. In view of the limited benefit of therapies such as hydration, bicarbonate and NAC, dialysis may seem like the definitive answer.

However, an excellent meta-analysis by Cruz et al—8 trials (6 randomized and 2 nonrandomized, controlled studies) were included in the analysis, with a pooled sample size of 412 patients—indicated that periprocedural extracorporeal blood purification (ECBP) does not significantly reduce the incidence of CIN in comparison with standard medical therapy. ECBP in the study consisted of HD (6 trials), continuous venovenous hemofiltration (1 trial), and continuous venovenous hemodiafiltration (1 trial).^[32]

Cruz et al found that the incidence of CIN in the standard medical therapy group was 35.2%, compared with 27.8% in the ECBP group. Renal death (combined endpoint of death or dialysis dependence) was 12.5% in the standard medical therapy group, compared with 7.9% in the ECBP group.

An important consideration is the role of ECBP therapy in patients with severe renal impairment (ie, stage 5 CKD) not yet on maintenance dialysis. A study by Lee et al indicated that in patients with chronic renal failure who are undergoing coronary angiography, prophylactic HD can improve renal outcome. The study included 82 patients with stage 5 CKD who were not on dialysis and who were referred for coronary angiography.^[33] The patients were randomly assigned to either undergo prophylactic HD (initiated within 81 ± 32 min) or to receive intravenous normal saline (control group).

The baseline creatinine of the dialysis group was 13.2 mL/min/1.73 m², comparable to that of the control group (12.6 mL/min/1.73 m²). The investigators’ primary endpoint was change in creatinine clearance in the 2 groups on day 4, which was found to be statistically significant (0.4 ± 0.9 mL/min/1.73 m² in the dialysis group vs 2.2 ± 2.8 mL/min/1.73 m² in the control group).

Lee et al found that 35% of the control group required temporary renal replacement therapy, compared with 2% of the dialysis group. In addition, long-term, postdischarge dialysis was required in 13% of the control patients but in none of the dialysis patients. Among those patients who did not require chronic dialysis, an increase in SCr at discharge of over 1 mg/dL from baseline was found in 13 patients in the control group and in 2 patients in the dialysis group.

The study, though hopeful, does raise some concerns. While the change in creatinine clearance on day 4 from baseline was statistically significant, the day 4 creatinine clearance itself was not significantly different between the 2 groups. Also, the results were not expressed as CIN incidence. This patient population is very fragile and is already on the verge of dialysis. How much time off dialysis a single HD session was able to buy these patients was not discussed. The duration of follow-up was also not clear.

Marenzi et al found better outcomes in patients who received venovenous hemofiltration both pre- and post-CM administration than in patients who received post-CM hemofiltration or no hemofiltration at all. These outcomes included a lower likelihood of CIN, no need for HD, and no 1-year mortality, in the pre-/post-CM group.^[34]

The biggest confounder in studies of continuous renal replacement therapy (CRRT) is that the outcome measure (SCr) is affected by the treatment itself. While the advantage of CRRT is the lack of delay in its institution, contrast clearance rates would be 1 L/h (16.6 mL/min provided a maximal sieving coefficient for contrast across the hemofiltration membrane of 1), substantially less than standard HD.

Furthermore, continuous venovenous hemofiltration is expensive, highly invasive, and requires trained personnel; the procedure itself needs to be performed in the intensive care unit (ICU). In the face of equivocal benefit of a highly invasive and expensive procedure, the role of continuous venovenous hemofiltration has yet to be accepted as a prophylactic treatment for avoiding CIN.

Dialysis immediately after contrast administration has been suggested for patients already on long-term HD and for those at very high risk of CIN. Three studies looked at its necessity and found that LOCM can be given safely to patients with ESRD who are being maintained on HD without the added expense or inconvenience of emergent postprocedural HD.

The only condition in which HD might be argued to have a beneficial role is in patients on peritoneal dialysis who rely on their residual renal function. In this setting, HD performed soon after CM administration may provide enhanced removal and therefore protect residual renal function. It should be noted, however, that these patients on peritoneal dialysis would therefore need an additional HD procedure with concomitant vascular access, as the clearance with peritoneal dialysis would be far too slow to offer any protection.

In a study to determine if renal replacement therapy in concert with contrast administration helps, Frank et al found that although the overall clearance of contrast was significantly increased by dialysis, the peak plasma concentration of iomeprol 15 minutes after contrast administration was not significantly changed by simultaneous dialysis. In their report, the investigators prospectively studied 17 patients with chronic renal insufficiency (SCr >3 mg/dL), dialysis independent, who were then randomized to receive high-flux HD over 6 hours simultaneously with contrast administration, and^[35]

In the study, Frank et al also found that to be clinically effective, simultaneous dialysis should reduce the risk of developing ESRD by 50%. If type 1 and type 2 errors are set at 0.01, the result could be accepted only if none of the 48 sequential patients with simultaneous dialysis required dialysis during the 8 weeks after contrast exposure. To reject the hypothesis, 239 sequential patients with simultaneous dialysis would have to be included. Therefore, most CIN studies, are seriously underpowered.

Studies of HD for CIN vary with respect to the definition of CIN used, the patient population, the type and volume of CM, how long after CM administration HD is started, and, finally, the dialysis treatment modality itself. While existing studies do not show HD to be superior to hydration alone for CIN prevention, if HD is used in conjunction with hydration and CIN protective therapy, such as NAC and bicarbonate, it might prove to be efficacious in some high-risk patients. However, most studies have had only an 8-week follow-up period. While the initiation of long-term dialysis was 5-15%, the progression to uremia over a long-term follow-up period is still unanswered.^[16]

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