Worsening Kidney Function -- What to Do With ACEIs and ARBs?

Robert W. Morrow, MD; Lynda A. Szczech, MD


July 31, 2012

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Robert W. Morrow, MD: Hi. This is Bob Morrow. I am a family physician from the Bronx, New York, and Associate Clinical Professor in the Department of Family and Social Medicine at the Albert Einstein College of Medicine. We are trying a new forum today. We are calling it "Primary Care Goes to Urinetown." Lynda Szczech, a nephrologist, is here with us. We are going to pose some questions over the next 3 sessions and see what she has to say. First, Lynda, would you introduce yourself?

Lynda A. Szczech, MD: Hello, Bob. My name is Lynda Szczech, and I am a nephrologist. I live in Durham, North Carolina, and I have the pleasure of being the President of the National Kidney Foundation. One of the things I would like to leave with everyone is that as you listen to our discussion, I hope you will take away a few good pearls. You also can find a lot of information at, including the National Kidney Foundation's clinical practice guidelines, which will be a bit dry compared with our discussion now but still chock-full of good information.

Dr. Morrow: Excellent. Thank you, Lynda. The first question reflects a challenge in my own practice: What should we do about adding angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers for the patient whose renal function is getting worse and worse? When do we increase the dose? When do we stop the dose? How do we decide? Lynda, what do you have to say about that difficult subject?

Dr. Szczech: The question of when to increase the dose is probably a good place to start. We need to think about urine protein excretion as the intermediate outcome. This is kind of similar to hemoglobin A1c. You want that number to be lower, so when you start an ACE inhibitor you assess urine protein excretion at baseline and you assess it again at 3 months. If this value is where you want it to be, that's great. If it is not, titrate up the dose of the ACE inhibitor [using urine protein excretion levels as your intermediate outcome] as you would with insulin or oral hypoglycemic, using hemoglobin A1c as the intermediate outcome.

Dr. Morrow: But when does that get you into trouble? When do you stop doing that?

Dr. Szczech: That is the finger on the garden-hose analogy that I always use: Angiotensin II is like your finger on the end of a garden hose; it causes the water to spurt out and increases pressure within the garden hose. If you take angiotensin II off, the water plunks out and the pressure within the hose is much less. It is good for a kidney to have that pressure within the glomerular network reduced, but it decreases filtration fraction because the pressure is less. It lowers everyone's calculated GFR (glomerular filtration rate) but does not hurt kidney function. Nonetheless, this always makes us nervous. We think that we have lost kidney function because of the ACE inhibitor, but we really have not. We have frame-shifted the reference range. You also must consider that the natural history of kidney disease is that it does progress. You will see a rise in creatinine in spite of good ACE inhibitor use. When you get to that grey area threshold of wondering whether the patient needs to start dialysis, we often want to treat ourselves or treat the number and make the patient more "euboxic." We want to make the numbers look less bad.

However, that is not the right decision. There is a great article from the RENAAL trial,[1] a study that looked at ACE inhibitors and angiotensin receptor blockers in patients with diabetic nephropathy and type 2 diabetes, during that time period right before initiation of dialysis. Staying the course with the ACE inhibitor actually does slow the time to requiring dialysis by a couple of months, which is not earth-shaking. If the potassium level becomes an issue, you are not doing the patient a disservice by discontinuing the ACE inhibitor; but if all is well, you are giving the patient a sweet couple of months by keeping the ACE inhibitor onboard and not just focusing on the numbers.

Dr. Morrow: That is very helpful, Lynda. Thank you. This is "Primary Care Goes to Urinetown," and we will return soon with a second presentation. Thanks very much for listening.


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