Putting Up
Roadblocks On The Path to Diabetic Kidney Disease
Evan David Rosen, M.D., Ph.D.
Assistant Professor of Medicine,
Harvard Medical School
One
of the most feared complications of diabetes is end-stage renal
(kidney) disease (ESRD). This condition, which requires either
dialysis or kidney transplantation, is reached in about 10%
of patients with type 2 diabetes and in 20% of type 1 diabetics.
Type 2 diabetes still accounts for the majority of cases of
ESRD, given the fact that it is so much more common than type
1 diabetes. And with type 2-diabetes on the rise in the United
States, the numbers for ESRD have gone up proportionately. Last
year alone, 90,000 Americans developed ESRD.
ESRD doesn’t just appear
out of the blue, however. The first stage of diabetic kidney
disease occurs when small amounts of protein are excreted in
the urine. The kidney normally acts as a filter to prevent proteins
in the blood from spilling into the urine - in diabetes the
filter becomes damaged and protein leaks through. Up to 60%
of diabetics will have such extra protein in their urine at
some point in their lives. In some of these patients, the amount
of protein that leaks through the filter gets larger and larger,
and eventually a series of pathological changes occur that lead
to wholesale kidney failure. Once this occurs, there is very
little that can be done other than dialysis or transplantation.
Given this unpleasant state
of affairs, efforts have been directed at preventing the earliest
form of kidney disease from appearing, or at least halting the
progression from small amounts of protein spilling to larger
quantities. The single most important factor appears to be good
sugar control, which is one of the major reasons why doctors
are always on their diabetic patients’ cases to get them
to reduce their blood glucose levels. Other factors can help
as well, such as reducing blood pressure and quitting smoking.
There is also a group of medications
that can help. These drugs are called ACE inhibitors, because
they inhibit a protein called Angiotensin Converting Enzyme.
ACE inhibitors are often prescribed for hypertension, but they
appear to have benefits that have nothing to do with blood pressure.
Commonly prescribed ACE inhibitors include captopril (CapotenTM),
lisinopril (ZestrilTM or PrinivilTM), enalapril (VasotecTM),
and ramipril (AltaceTM). Studies performed several years ago
showed that ACE inhibitors prevent the onset and progression
of early diabetic kidney disease in type 1 diabetes. Several
smaller studies also suggested that ACE inhibitors were similarly
useful in type 2 diabetes, and certainly the majority of diabetes
specialists have used ACE inhibitors liberally in such patients.
Now, three papers have appeared
back to back to back in the latest issue of the New England
Journal of Medicine, looking at the use of drugs called angiotensin
II receptor antagonists, or ATII blockers, in type 2 diabetes.
The most common ATII blockers on the market include irbesartan
(AvaproTM), valsartan (DiovanTM), and losartan (CozaarTM). These
drugs work in a similar way to ACE inhibitors, so it comes as
not much of a surprise that they prevent the progression of
diabetic kidney disease. Still, it’s nice to get confirmation
of this assumption in three separate large trials. Furthermore,
two of the studies looked specifically at patients with moderate
amounts of protein in their urine, and showed a 16-23% reduction
in the development of ESRD and death.
This is all to the good, of
course. I just think it’s important to mention a few things
that may help you if you’re a patient with type 2 diabetes,
or a physician taking care of such patients. First, I believe
strongly that ACE inhibitors are the first option in the prevention
of diabetic nephropathy, for both type 1 and type 2 diabetes.
They have been around longer than ATII blockers, we know them
better, and frankly, they are at least half as expensive. This
last fact, coupled with the fact that ACE inhibitors will soon
be off patent and will thus be even cheaper, is why these drug
company funded studies were performed only with ATII blockers
and did not include ACE inhibitors. It is true that in about
5-20% of people, ACE inhibitors can cause a benign (albeit annoying)
cough. It is my practice to use ATII blockers only in those
patients who develop such a cough on ACE inhibitors. Second,
patients with diabetes who also develop high blood pressure
(an extremely common combination) should be treated with an
ACE inhibitor (or ATII blocker if a cough develops) before trying
other blood pressure medications. This is to give the double
benefit of blood pressure reduction and protection from diabetic
kidney disease in one pill.
It pains me to think of all
the patients I have seen in consultation who have early diabetic
kidney disease and who are taking several expensive pills for
hypertension that do not include an ACE inhibitor. Finally,
neither ACE inhibitors nor ATII blockers are a substitute for
good sugar control. It is important that patients are not left
with the impression that these drugs totally eliminate the risk
of diabetic kidney disease. The most important factor is still
maintaining a near normal glucose level. Furthermore, neither
ACE inhibitors nor ATII blockers protect against other complications
of diabetes like retinopathy (eye disease) and neuropathy (nerve
damage) - only good glucose control can prevent these conditions.
References:
1. Lewis E. J., Hunsicker L.
G., Clarke W. R., Berl T., Pohl M. A., Lewis J. B., Ritz E.,
Atkins R. C., Rohde R., Raz I., the Collaborative Study Group.
Renoprotective Effect of the Angiotensin-Receptor Antagonist
Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes.
New England Journal of Medicine 2001; 345:851-860, Sep 20, 2001.
2. Brenner B. M., Cooper M. E.,
de Zeeuw D., Keane W. F., Mitch W. E., Parving H.-H., Remuzzi
G., Snapinn S. M., Zhang Z., Shahinfar S., the RENAAL Study
Investigators. Effects of Losartan on Renal and Cardiovascular
Outcomes in Patients with Type 2 Diabetes and Nephropathy. New
England Journal of Medicine 2001; 345:861-869, Sep 20, 2001.
3. Parving H.-H., Lehnert H.,
Brochner-Mortensen J., Gomis R., Andersen S., Arner P., the
Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria
Study Group.The Effect of Irbesartan on the Development of Diabetic
Nephropathy in Patients with Type 2 Diabetes. New England Journal
of Medicine 2001; 345:870-878, Sep 20, 2001.
Written by Evan D. Rosen, M.D.,
Ph.D.
Content created 9/26/01
Content last reviewed September 26, 2001
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