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A validation of recent increasing concerns of the role of ACE-Is and ARAs in AKI epidemic around the world.

Posted by nneooonuigbo on 02 Dec 2013 at 13:47 GMT

We read with amazing interest, the recent superbly designed and executed investigative analysis by Tomlinson et al of ACEI and ARA prescribing trends in the UK, and the demonstration that up to 15% of the increase in AKI admissions in England over a 4-year time period was potentially attributable to the increased prescribing of ACE-Is and ARAs [1]. As was very aptly acknowledged by the authors, since the introduction of ACE-Is and ARAs, the indications for their use has escalated over the last two decades to include a number of chronic conditions including hypertension, CKD with proteinuria, and heart failure with left ventricular dysfunction. The authors had reported that ACE-Is and ARAs now represented the second most commonly prescribed medicines in English primary care, accounting for 6% of all prescriptions [2]. Similarly, here in the US, some studies have demonstrated that nearly 80% of some US diabetic patients are receiving an ACE-I, an ARA or a combination of both agents [3-5].
In a report published in 2009 in the journal, Hemodialysis International, we had observed that simultaneous with this escalating albeit evidence-based increase in the utilization of ACE-Is and ARAs, there had continued to be experienced, an increasing epidemic of AKI both in community-based and in hospital-based studies [6]. We acknowledged that even though other factors would be contributing to this AKI epidemic, we further opined that recent published data had raised concerns of a plausible connection between increased use of the RAAS blocking agents and this AKI epidemic [6]. In that same Hemodialysis International article, we had reported on three cases of AKI treated in the ICU of our 4-nephrologist Northwestern Wisconsin practice, all seen over a 3-day Christmas weekend in 2007, where severe and potentially life-threatening AKI, often with hyperkalemia, sometimes requiring dialysis intervention, were clearly causatively associated with concurrent use of ACE-I or ARA therapy [6]. One of them was a renal transplant recipient [6].
Clearly, according to various accounts, from hospital-based and community-based studies, the United States is experiencing an AKI epidemic [7,8]. Hsu et al. showed that between 1996 and 2003, the incidence of nondialysis requiring cases of community-based AKI increased from 322.7 per 100,000 person-years to 522.4 per 100,000 person-years [8]. Similarly, the incidence of dialysis-requiring AKI increased from 19.5 per 100,000 to 29.5 per 100,000 person-years [8].
We conclude that the report by Tomlinson et al has validated our concerns that the increasing use of ACE-Is and ARAs over the last two decades has clearly contributed to the AKI pandemic around the world [1,6-8]. We introduced the terminology of Renoprevention in an article published in 2009 in the Quarterly Journal of Medicine, where we strongly advocated for the preemptive albeit temporary withholding (for upwards of a week) of ACE-Is and ARAs (and other nephrotoxics including NSAIDs) in older CKD patients during acute illness, before iodinated contrast exposure and before major elective surgical procedures [9]. In a more recent analysis, we have further demonstrated the practicality and economic economic impact of this new reengineered paradigm of preemptive withholding of RAAS blockade in critically sick patients in our ICUs [10].

1. Tomlinson LA, Abel GA, Chaudhry AN, Tomson CR, Wilkinson IB, Roland MO, Payne RA. ACE Inhibitor and Angiotensin Receptor-II Antagonist Prescribing and Hospital Admissions with Acute Kidney Injury: A Longitudinal Ecological Study. PLoS One. 2013 Nov 6;8(11):e78465. doi: 10.1371/journal.pone.0078465.
2. National Health Service. The Information Centre. Prescription Cost Analysis, England (2011) Available: Accessed 25 February 2013.
3. Carter BL, Malone DC, Ellis SL, Dombrowski RC. Antihypertensive Drug Utilization in Hypertensive Veterans With Complex Medication Profiles. J Clin Hypertens (Greenwich) 2000; 2:172–80.
4. Nelson CR, Knapp DA. Trends in antihypertensive drug therapy of ambulatory patients by US office-based physicians. Hypertension 2000; 36:600–3.
5. Scarsi KK, Bjornson DC. The use of ACE inhibitors as renoprotective agents in Medicaid patients with diabetes. Ann Pharmacother 2000; 34:1002–6.
6. Onuigbo MA. Does concurrent renin-angiotensinaldosterone blockade in (older) chronic kidney disease patients play a role in the acute renal failure epidemic in US hospitalized patients?—Three cases of severe acute renal failure encountered in a northwestern Wisconsin Nephrology practice. Hemodialysis International 2009; 13:S24–S29.
7. Centers for Disease Control and Prevention (CDC). Hospitalization discharge diagnoses for kidney disease— United States, 1980–2005. MMWR Morb Mortal Wkly Rep. 2008; 57:309–312.
8. Hsu CY, McCulloch CE, Fan D, Ordon˜ ez JD, Chertow GM, Go AS. Community-based incidence of acute renal failure. Kidney Int. 2007; 72:208–212.
9. Onuigbo MA. Reno-prevention vs. reno-protection: a critical re-appraisal of the evidence-base from the large RAAS blockade trials after ONTARGET--a call for more circumspection. QJM. 2009 Mar;102(3):155-67. doi: 10.1093/qjmed/hcn142. Epub 2008 Dec 19.
10. Onuigbo MA. Renoprevention: A new concept for reengineering nephrology care--an economic impact and patient outcome analysis of two hypothetical patient management paradigms in the CCU. Ren Fail. 2013;35(1):23-8. doi: 10.3109/0886022X.2012.741644. Epub 2012 Nov 15.

No competing interests declared.

RE: A validation of recent increasing concerns of the role of ACE-Is and ARAs in AKI epidemic around the world.

LTomlinson replied to nneooonuigbo on 04 Dec 2013 at 16:00 GMT

Dear Dr Onuigbo,
Thanks very much for your comments. We have been very much aware of your previous work on this topic and the points you raise. I have moved on to looking at individual level data and will hopefully have more to report soon
Best wishes

No competing interests declared.