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.


The ACEI, captopril was introduced into clinical medicine in the early 1970s for hypertension. Other ACEIs and the ARBs were introduced subsequently. Following several RAAS blockade trials, we now have an expanded set of clinical indications for these agents. Despite the escalated use of these agents, we continue to experience an unexplained epidemic of ESRD/CKD/ARF. There are concerns regarding potential iatrogenic renal failure arising from these agents. A case, it would appear, of unintended consequences. Our publication of several reports on the previously unrecognized syndrome of late onset renal failure from angiotensin blockade (LORFFAB) in 2008 adds to this evolving literature. At the same time, some recent reports have questioned the veracity of claims of superior reno-protection with these agents beyond BP lowering. A post hoc analysis of a subset of patients in the MICRO-HOPE cohort suggested that a previously unrecognized greater 24-h BP lowering achieved in the ramipril arm vs placebo could explain the reported benefits of the ACEI. These doubts and concerns became heightened by the results of the ONTARGET study. Our critical re-appraisal of the large RAAS blockade trials revealed design flaws and protocol contradictions that further these doubts and concerns. We conclude that these agents be used more judiciously, with better monitoring of kidney function. Treating physicians must consider drug discontinuation in selected patients. We also support temporary withdrawal of these agents before major surgical procedures, contrast media administration and during acute illness. Such preventative measures (reno-prevention) would enhance the benefits of reno-protection with RAAS blockade.

Publication types

  • Review

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / adverse effects*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Evidence-Based Medicine / methods*
  • Humans
  • Hypertension / drug therapy*
  • Kidney Failure, Chronic / chemically induced*
  • Proteinuria / diagnosis
  • Proteinuria / therapy*
  • Randomized Controlled Trials as Topic


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors