Blog entry by Meguid El Nahas

Anyone in the world

The answer to this question is usually that ACE inhibitors and ARBs have a protective effect by slowing the progression of CKD.

Yet, in all studeis on inhibition of RAAS and CKD progression diabetic or otherwise, there hasn't been a single study that reported the impact of the intervention on GFR. Instead, all the studies on ACE inhibition and progression since that of Lewis et al in 1993 relied on surrogate markers of progression namely: serum creatinine, creatinine clearance, 1/Cr slopes against time or more recently estimatedGFR. Not a single study published to my knowledge solid data on the hard and relevant endpoint of measured GFR and changes with time???!!!!

Authors have overlooked that changes in serum creatinine and derived formulation can be due to one of 4 factors:

1. Impact on dietary intake of amino acids or creatine

2. Creatine/Creatinine metabolism

3. GFR

4. Tubular secretion

So changes upon ACE inhibition in serum creatinine could be due to any one of these 4 confounders; yet nobody seems to take that into consideration and equate changes in serum creatinine to changes in GFR only....Why I ask myself this oversight????

This, in spite of evidence to suggest that inhibition of the RAAS system impacts on :

1. Efferent arterioles; leading to vasodialtation

2. Increased peritubular capillary circulation secondary to improved efferent arteriolar blood flow

3. Increased tubular secretion of creatinine either indirectly through 1 and 2 or directly through an increase in its organic cationic transporters (OCT1 and 2) that affect creatinine secretion by the proximal tubules (ref 1,2).

In conclusion, the oberved effect of RAA system inhibition of the rate of decline of serum creatinine may be simply the reflection of increased tubular secretion of creatinine rather than anything to do with prevention of GFR decline as the latter has never been measured!? Clearly, this is a hypothesis as much as the assumption that inhibition of RAAS slows the decline of true GFR!

Isnt it intriguing that investigators studying the progression of CKD never reported measured changes in GFR....I wonder why????


1. Thomas MCTikellis CBurns WCThallas VForbes JMCao ZOsicka TMRusso LMJerums GGhabrial HCooper ME,Kantharidis PReduced tubular cation transport in diabetes: prevented by ACE inhibition.Kidney Int. 2003 Jun;63(6):2152-61.

2. Thomas MCJerums GTsalamandris CMacisaac RPanagiotopoulos SCooper MEMDNSG Study GroupIncreased tubular organic ion clearance following chronic ACE inhibition in patients with type 1 diabetes.Kidney Int. 2005 Jun;67(6):2494-9.
[ Modified: Thursday, 1 January 1970, 1:00 AM ]