Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

Abstract

Current epidemiological data from the USA, Europe, Asia and the Indian subcontinent, Africa, the Far East, South America, the Middle East and Eastern Europe all point to the increasing incidence of renal failure encompassing acute kidney injury (AKI), chronic kidney disease (CKD) and end-stage renal disease (ESRD). While the explanations for these worldwide epidemics remain speculative, it must be acknowledged that these increases in AKI, CKD and ESRD, happening worldwide, have occurred despite the universal application of strategies of renoprotection over the last 2 decades, more especially the widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We note that many of the published large renin-angiotensin-aldosterone system (RAAS) blockade randomized controlled trials, upon which current evidence-based practice for the increasing use of ACEIs and ARBs for renoprotection derived from, have strong deficiencies that have been highlighted over the years. From reports in the literature, there is an increasing association of exacerbations of renal failure with ACEIs and ARBs, more so in the older hypertensive patient, >65 years old. The biological plausibility for ACEI and ARB to protect the kidneys against a background of potential multiple pathogenetic pathways to account for CKD progression appears to be not very defensible. We reviewed the literature along these lines and submit that ACEIs and ARBs often cause unrecognized significant worsening renal failure in CKD patients, sometimes irreversible, and that more caution is required regarding their use, especially in the older hypertensive patients, with likely ischemic hypertensive nephropathy. Given the increasing association of concomitant RAAS blockade with worsening renal failure following exposure to iodinated contrast, during acute illness, in the perioperative period and following lower bowel preparations prior to colonoscopy, we submit that, preferably, ACEIs and ARBs be withheld for 2–4 days prior to or during these clinical scenarios. This represents the concept of renoprevention.

The Impact of Renin-Angiotensin-Aldosterone System Blockade on Contrast-Induced Nephropathy: A Meta-Analysis of 12 Studies with 4,493 Patients

“…Another strength of our study is the newly adopted analysis according to the status of chronic exposure to RAAS blocker, which has not been employed in previous meta-analyses or narrative reviews on this issue [16,17,18,19]. The major findings of this meta-analysis are that ACEI/ARB discontinuation in chronic users before contrast procedure is associated with less deterioration of renal function, whereas acute intervention of ACEI/ARB intake in drug-naïve patients did not affect CIN incidence.…”

Proteinuria as a Risk Marker for the Progression of Chronic Kidney Disease in Patients on Predialysis Care and the Role of Angiotensin-Converting Enzyme Inhibitor/Angiotensin II Receptor Blocker Treatment

“…This practice was recently supported by a study that showed a delayed onset of RRT after the discontinuation of ACEi/ARBs in advanced CKD patients (stages IV–V) [22]. Furthermore, a debate is ongoing concerning the general applicability of the many trials showing a delayed progression to end-stage renal disease when treated with ACEi/ARBs in patients with mainly CKD stages I–IV [23]. …”

Predictors of Acute Kidney Injury in Geriatric Patients Undergoing Total Knee Replacement Surgery

“…Onuigbo et al stated that for renal protection in the elderly with underlying CKD, it is reasonable to discontinue ACEI/ARB two to four days prior to elective surgeries or invasive procedures with risk of AKI (55). The same seems to be correct in the elderly who are undergoing elective joint surgeries and are at risk for AKI.…”