Renoprevention Revisited - The Impact of Preemptive Withdrawal of RAAS Blockade prior to Iodinated Contrast Exposure in Older CKD Patients: Results of a New Meta-Analysis

Contrast-induced nephropathy (CIN) is the third leading cause of new-onset acute kidney injury (AKI) in hospitalized patients in the USA [1]. Furthermore, AKI from CIN needing dialysis portends increased inhospital mortality approaching 40%, together with a low 2-year survival of <20% [2,3]. Nevertheless, the role of renin-angiotensin-aldosterone system (RAAS) blocking agents, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in the pathophysiology of CIN remains controversial as the available literature is conflicting and discordant [4,5,6,7,8,9,10,11]. Whereas some reports suggest that prior initiation of RAAS blockade before iodinated contrast exposure mitigates the severity and incidence of CIN [4,5], others show exactly the opposite effect, i.e. that concurrent RAAS blockade in fact exacerbates these [6,7,8,9,10]. Furthermore, discontinuation of RAAS blockade before the exposure can reduce the incidence and severity of CIN [10,11]. Indeed, Komenda et al. [10 ]reported a prospective Canadian case series on 31 chronic kidney disease (CKD) patients, with a mean age of 64 years and mean eGFR of 34 ml/min/1.73 m2. All patients received iodinated contrast and had ACEI, ARB and diuretics withheld 1 day before iodinated contrast exposure and restarted 2 days afterwards. Their study demonstrated stable renal outcomes for up to 26 months after the contrast exposure, with no change in CKD stage when compared with historical controls [10]. It is to be noted that in selected patients in this study, amlodipine (5 mg/day) was substituted to control hypertension [10]. It is against this background that we read with excitement the recent meta-analysis by Jo et al. [12 ]on the impact of RAAS blockade on CIN. This meta-analysis of 12 studies involved 4,493 patients [12]. This report represented the largest such meta-analysis on the effects of concurrent angiotensin inhibition on contrast-induced nephropathy. The methodology, particularly the disparate statistical subgroup analysis distinguishing between the different ACEI/ARB study patient ‘phenotypes', was very commendable [12]. The major findings, i.e. that ACEI/ARB discontinuation in chronic users before iodinated contrast exposure is associated with less deterioration of renal function but that acute preprocedure intervention with ACEI/ARB therapy in drug-naïve patients did not affect the incidence of CIN, should receive stronger positive acknowledgement from the nephrology and general medicine community [12]. This care model or paradigm is very much in line with one of our touted measures of ‘renoprevention' as we have repeatedly reported from our Mayo Clinic Health System Unit here in northwestern Wisconsin [13,14].Once again, the meta-analysis by Jo et al. [12] touted the preemptive temporary discontinuation of ACEI/ARB prior to iodinated contrast administration in older CKD patients to limit the severity and incidence of CIN [12]. In the last few years, we have continued to tout the concept of renoprevention [13,14]. By ‘renoprevention', we mean all the preventative practices that would potentially eliminate or at least alleviate the incidence of AKI in (especially older) CKD patients [13,14]. Prevention is indeed better than cure [13,14]. Except for the institution of renal replacement therapy, modern medicine has yet to devise a cure for AKI. Undeniably, at least for now, no specific pharmacologic therapy is effective in patients with established AKI, and the care of such patients is limited to supportive treatment and, of course, renal replacement therapy when indicated [15]. We support the increasing application of the principles of ‘renoprevention' which would include the deliberate protocolized prevention or rapid correction of perioperative hypotension, together with the deliberate preemptive withdrawal or avoidance of all potential nephrotoxic exposures in the perioperative period, before the administration of iodinated contrast and during concurrent serious illnesses [13,14,15,16,17]. Such nephrotoxic exposures would include diuretics, nonsteroidal anti-inflammatory drugs, ACEI/ARB and aminoglycosides among others [13,14,15,16].

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