Is “Renalism” No Longer an Obstacle to Angiography and Intervention in Patients With Chronic Kidney Disease?

Most coronary interventionists have concerns about angiography exacerbating renal function via the use of contrast medium because the incidence of iodinated contrast-induced acute kidney injury (CI-AKI) is known to be associated with poor prognosis.¹ “Renalism” is a term coined to describe the reluctance of clinicians to conduct angiography and intervention in the presence of chronic kidney disease (CKD) in patients with suspected atherosclerotic disease. Data from a large registry confirmed the effects of “Renalism”: the presence of CKD indeed caused inappropriately low rates of coronary angiography, and the underuse of coronary angiography was related to significantly higher 1-year mortality.² Thus, clinical decisions for CKD patients require balancing the risk and potential benefit of an invasive strategy inclusive of angiography.

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Here, let us reconsider whether the use of contrast medium is truly associated with the poor prognosis of patients undergoing angiography and percutaneous coronary intervention (PCI). In a large meta-analysis of 39 observational studies, the incidence of CI-AKI was shown to be associated with an increased risk of death and cardiovascular events.³ However, as we know, the results derived from observational studies cannot discriminate whether poor clinical outcomes were attributed to the use of contrast medium per se or to the patients’ intrinsic baseline conditions, even if confounding factors were mathematically adjusted. A randomized controlled study (ISCHEMIA-CKD trial), comparing invasive vs. conservative strategy for the treatment of advanced CKD patients with ischemic heart disease, illustrated that periprocedural initiation of dialysis occurred in 2.1% of invasively treated vs. 0.6% of conservatively managed participants. Subsequently, the different between invasive and conservative strategies converged: 3-year cumulative rates of dialysis initiation were 24.1% vs. 25%, respectively. In this context, the study also demonstrated no significant difference in 3-year cumulative incidence of cardiovascular death, myocardial infarction (MI), hospitalization for unstable angina or heart failure, or resuscitated cardiac arrest (35.1% vs. 35.1% for invasive and conservative treatment, respectively).⁴ Those results collectively suggest that the use of contrast medium increases the risk of CI-AKI during the periprocedural period but its effects are clinically irrelevant over the long term.

Then, another question arises in the management of CKD patients with regards to whether the timing of initiation of renal replacement therapy affects the clinical outcome. In an observational study of 10,290 patients with advanced CKD, compared with late dialysis initiation at estimated glomerular filtration rate (eGFR) 6–7, early initiation at eGFR 15–16 was associated with a 5.1% lower absolute 5-year mortality risk and 2.9% lower risk of a major adverse cardiovascular event.⁵ A randomized controlled trial (IDEAL trial) compared early planed initiation of dialysis (eGFR 10–14) vs. late initiation of dialysis (eGFR 5–7) and demonstrated no significant difference in the incidence of cardiovascular events, infections, or complications of dialysis during a median follow-up period of 3.6 years, albeit a shorter time to initiate dialysis in the early initiation than in late initiation group by 5.6 months.⁶ Those results corroborated that early initiation of renal replacement therapy would not necessarily lead to poor clinical prognosis in severe CKD patients, although early initiation of dialysis might impose on the patients the burden of a substantially longer period spent on dialysis.

Several attempts have been made to suppress the incidence of CI-AKI by reducing the volume of contrast medium used during angiography and the interventional procedure. In the MOZART trail, compared with conventional angiography-based PCI, the volume of contrast agent was reduced from 64.5 to 20 mL per procedure by the use of intravascular ultrasound (IVUS).⁷ Other data from a multicenter registry showed zero incidence of CI-AKI and 1-year all-cause deaths by reducing the ratio of contrast volume/eGFR <1 through IVUS-guided PCI.⁸ Intriguingly, there is a different approach to minimizing the contrast volume by utilizing intravascular imaging optical coherence tomography (OCT). Kurogi et al demonstrated in 8 preliminary cases that OCT-guided PCI was successfully accomplished with the use of only 17.5 mL [6.5, 25.5] of contrast medium with the aid of 76 mL [57, 120] of low-molecular-weight dextran.⁹

In this issue of the Journal, Shibata et al¹⁰ document the feasibility and safety of their “zero-contrast” IVUS-guided PCI strategy from registry data of 55 patients with ≥Stage 3 CKD. Zero-contrast PCI is defined as PCI without contrast until the final IVUS assessment. Contrast use was not permitted even if the patient had chest pain or ST changes on ECG. The zero-contrast strategy was accomplished in all of the 78 procedures in the 55 patients without any complications such as wire perforation, distal embolism, residual dissection/hematoma, or periprocedural MI. Accordingly, the mean contrast volume used during PCI was 4.3 mL (3.5–5.3). There was no incidence of CI-AKI. During an average of 32 months’ follow-up, 3 of 5 (60%) stage 5 CKD, 1 of 8 (12.5%) stage 4 CKD, and 0 of 42 (0%) stage 3 CKD patients commenced hemodialysis. Those numbers for initiation of hemodialysis were lower than those for non-diabetic hypertensive CKD patients,¹¹ but probably comparable to those for the natural course in the general CKD population. Further, the authors indicated the possibility that zero-contrast PCI could improve renal function via the cardiorenal relationship. However, that statement remains speculative until it is confirmed in a randomized trial comparing the zero-contrast PCI strategy with conservative strategy in the CKD population.

At any rate, judging from the data currently available, there is little evidence that the use of contrast medium does directly harm the clinical prognosis of CKD patients in the long run (at least in units of years). The only concern is the burden of a prolonged period of dialysis for patients suffering from CI-AKI but now we have a solution: “zero- or minimum-contrast PCI supported by intravascular imaging”. Why do you still hesitate to perform angiography by adhering to “Renalism” in the management of CKD patients suspected of having atherosclerotic disease?

Conflict of Interest

The authors declare no conflicts of interest in association with this study.

References

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