Blog entry by Meguid El Nahas

Anyone in the world

On Tuesday of this week, the ALTITUDE study investigating the effect of Aliskerin (a renin antagonist) on Diabetic Nephropathy has been stopped for lack of efficacy.

Is that another nail in the coffin of RAAS inhibition in CKD and Diabetic Nephropathy or is it a misunderstanding of the nature of modern day diabetic kidney disease?

Increasingly the patients with diabetes and CKD we see at the Sheffield Kidney Institute are older T2DM patients with longstanding hypertension, often predating the diagnosis of DM, atherosclerosis and minimal (<1g/24h) proteinuria; those are likely to have renal atherosclerosis and ischemic nephropathy. These are unlikely to respond to RAAS inhibition and may in fact be harmed by these agents and their combination (see data from ONTARGET).

The RAAS inhibition story in DN started in 1984 in experimental animals (Zatz et al/Brenner et al.) of T1DM. They were apparently confirmed in the Lewis study published in NEJM in 1993 , but when you read carefully this publication you realised the patients selection bias; those with heavy proteinuria at baseline were in the placebo group, those with milder proteinuria in the captopril group...so selection bias from onset not to mention the fact that BP systolic and diastolic was lower in the captopril group!  Consequently, if beneficial at all these agents would be best used in young, T1DM with heavy proteinuria reflecting severe microvascular disease...not older T2DM with ATS and renal ischemia...

So perhaps, it is high time for nephrologists worldwide to:

1. Distinguish diabetic nephropathy (T1DM) and diabetic nephropathy (T2DM)

2. Get off the RAAS inhibition bandwagon as this approach can do more harm than good if patients selection is not carefully considered.

In fact, we published preliminary data suggesting that STOPPING  these agents in T2DM may lead to IMPROVEMENT in the kidney function of some patients with T2DM and advanced CKD (Ahmed et al, 2011)!

[ Modified: Thursday, 1 January 1970, 1:00 AM ]