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Why ACE inhibitors are contraindicated in bilateral renal artery stenosis ?

Posted Sep 01 2010 10:53am

It is traditionally believed  , renal blood flow is critically determined by the  luminal diameter  of  renal artery.But in reality  there are more important factors  other than renal  arterial diameter  that determine the glomerular  blood flow.  As in any vascular bed, it is the arterioles that determine the resistance and hence the flow . These arterioles  form the  critical  resistance  points and acts as   check  valves in this  “vascular  highway”  flowing across the renal terrain !

Unlike other micro-circulations ,  the kidneys have a  special job to do ,  ie filtering  the toxic  molecules. Hence,   for the blood entering the kidneys  , even  nourishing the kidney seems ,  a less important  function !  The nephrons  of the kidneys are probably the most “high – tech” cells in human body (Of course ,next only to brain cells ) .The vascular  tuft of glomerulus located within the bowman’s capsule  is perfused  by afferent arteriole and drained by efferent arteriole .

The entry of blood into glomerulus is regulated both by afferent and  efferent arteriolar  tone .These  two micro-circulaoty units  are under the  sensitive control of both neural  and humoral  signals. Glomerular circulation is meticulously  regulated by renal juxta glomerular apparatus.It modulates the glomerular  blood flow by secreting renin which  acts through Anigiotensin 2  on the   efferent arteriole .

The tone of the  efferent  arteriole  is thought to be the single important factor in this servo control mechanism.

What happens in bilateral renal arterial stenosis ?

When there is bilateral renal arterial stenosis the effective renal blood flow is not  significantly reduced , but maintained at  the cost of increasing the efferent arteriolar constrictor tone.It  is  like a  check valve at  the  exit point of a dam , which is partially closed to maintain the adequate pressure head (Here , intra-glomerular  pressure head )

What happens when ACEI are introduced ?

Once ACE inhibitors administered , the efferent arteriolar   tone is removed , this triggers  the intra glomerular pressure to drop  suddenly and filtration pressure reduces .

Note: ACEI does  not reduce the renal  blood flow  directly  but  the glomerular  perfusion pressure drops hence precipitating acute renal function deterioration

What is your comment about the reno-protective effects of ACEI ?

The medical science’s  most  crucial  moments are , when we confront , two diagonally opposite views  are being debated  and both  suggest , there is definite benefit for the patient ! Cardiologists and nephrologists were always  made to believe  , that ACEI are  unfriendly to kidneys .But ,we now have  evidence , ACEI is not an untouchable molecule in renal  dysfunction.

This is based on  the observations made , over the years that  excess Angiotensin 2  is  ultimately a liability for the kidneys !

Lookin at a  long  term perspective  , AT 2  increases the intra -glomerular hypertension and ACEI inhibitors reduce it.This  pr0tects the  nephrons from  hyper-filtration  mode ,  that accelerates the  glomerular  injury . So , the  current thinking seems to suggest ACEI has a definite role in arresting the progress of  renal cell injury .

This is akin to beta blocker story in CHF which was initially contraindicated in CHF later became a definite indication

The only issue for ACEI is , it should not be continued if an ARF like picture sets in .(Acute deterioration ). Otherwise ,  in CRF at any  basal level of serum creatinine  , ACEI can be continued . Some think even an  increase by few mg of creatinine  can be allowed .

So the following can be a working guideline *

  • ACEI can be started  or continued at any level of creatinine in stable CKD with or without dialysis

But ,ACEIs need to be stopped in all of the following 

  • Acute renal failures
  • Acute on chronic renal  failure
  • Accelerated elevation of  creatinine  (As in bilateral renal artery stenosis)

How much elevation of creatinine is allowed in CKD  with ACEI  ?

This is   not answered yet .

*Caution : The above conclusions on ACEI and creatinine was  derived  by me , based on  with  personal discussions with my  Nephrology colleagues. It may  be subjected to correction.

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