August 20, 2009

Proteinuria: Is the ONTARGET renal substudy actually off target?

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ONTARGET showed that dual renin–angiotensin system blockade prevents microalbuminuria but facilitates transient renal function impairment in nonproteinuric patients with atherosclerotic vascular disease or diabetes. This articles suggests that these findings should not be used as an excuse not to optimize renin–angiotensin system inhibition and target urinary protein in patients with proteinuric nephropathies.

Related Articles:

Chronic Kidney Disease, RAS Blockade
  • Diarrhea was more common with combination therapy than either agent alone in ONTARGET. It would be interesting to see detailed data to see, if the occurrence of acute renal failure requiring dialysis was more common in this group of patients and in patients, as RAAS blockers [irrespective of whether a single agent or combination], can precipitate ARF because of voulme depletion. I agree that this was a side-effect or a complication of RAAS use with volume depletion from any cause, rather than a negative renal end point.

    As I stated earlier [in relation to ONTARGET study – I am not sure, if my slides are still on this-site] that ONTARGET results should be applied to ONTARGET POPULATION and patients with proteinuric CKD were NOT Included in the study and we shouldn’t [if one really wish to practice evidence-made medicine] apply these results to this group of patients.

  • I agree completely with the sentiment of this article. The analysis of the ONTARGET study by commentators around the world is both sloppy and damaging to the the principles of CKD management. I would like to point out that, unless I’m mistaken, in the IDNT and RENAAL studies, no data was available on acute renal failure. It is expected that in these studies, even one RAS medication could have precipitated acute renal failure requiring dialysis (just as a small number of patients in ONTARGET did in the monotherapy groups). Yet in IDNT and RENAAL there was a 20% reduction in hard clinical end-points that easily outweighed any harm that may have been observed, though wasn’t reported. In ONTARGET, these patients were at VERY LOW RENAL RISK. And therefore, any expectation of renal benefit is trivial, whereas even a small amount of harm could be shown to be statistically significant, which it was in this study of 25,500 patients. The renal ONTARGET study and the pervasive analysis of it, was extremely disappointing.