Renal
Scleroderma
By the late Joseph
Korn, M.D., Alan S. Cohen Professor of Medicine in Rheumatology,
and Director, Section of Rheumatology and Arthritis Center,
Boston University School of Medicine (originally published
in "Scleroderma Voice," 2003 #1)
Editor's note:
You can skip directly to the subheads that interest you, by
clicking on these links:
Kidney disease
is one of the manifestations of vascular, or blood vessel
involvement, in scleroderma.
Other manifestations
of vascular disease in scleroderma include Raynaud's phenomenon,
telangiectasia (dilated blood vessels, most common on the
face and hands), and pulmonary hypertension.
In all of these,
it appears that initial events are damage to the inner lining
of blood vessels, abnormal constriction of blood vessels (which
is at first reversible), and subsequent structural changes
in the blood vessel with overgrowth of the lining cells of
blood vessels and deposition of scar tissues in the blood
vessels.
The term "vasculopathy"
has been applied to blood vessel disease in scleroderma. The
initiating events for this vasculopathy are unknown.
Renal Involvement: Early
Treatment Is Crucial
Until 25 years
ago, kidney disease was the leading cause of death in scleroderma.
That picture has
changed with the availability of a new class of drugs called
angiotensin converting enzyme (ACE) inhibitors, which have
had a profound effect on the ability to treat kidney disease
in scleroderma.
Nonetheless, involvement
of the kidneys in scleroderma remains an important event that
can lead to loss of kidney function, the need for dialysis,
and secondary effects on the heart and lungs. The ability
to recognize renal involvement early and to institute therapy
immediately remains the most important bulwark against devastating
renal involvement.
What Is Scleroderma Renal Crisis?
The term "scleroderma
renal crisis" has been used to characterize kidney involvement
in scleroderma, because of the abrupt and potentially devastating
consequences of kidney disease.
The onset of renal
crisis is generally heralded by an abrupt rise in blood pressure,
which can occur over a matter of days to weeks.
This is associated
with declining kidney function (measured as a rise in the
serum creatinine or a decline in "creatinine clearance"),
the appearance of protein in the urine, and, in more advanced
stages, accompanying heart failure.
How Does Scleroderma Renal Crisis
Develop?
The events that
lead to this crisis are imperfectly understood, but appear
to involve at first constriction of blood vessels within the
kidney, followed by actual scarring of these vessels with
growth of the lining cells of blood vessels (endothelial cells
and smooth muscle cells), and deposition of fibrin, the material
that forms blood clots, inside the vessel.
The process tends
to involve medium-sized blood vessels in the kidney. As a
result of impaired blood flow in the kidney, kidney hormones
are released that bring on a cascade of blood vessel constriction
and further impaired blood flow.
There may be injury
or actual death of parts of the kidney, both as a result of
the initial process and the ensuing severely high blood pressure.
The high blood
pressure and constricted and occluded (blocked) blood vessels
present an impediment to normal heart function, and some component
of heart failure is common.
Because blood vessels
are literally occluded, red blood cells are sheared as they
pass through the blood vessels, leading to their destruction;
this is called microangiopathic hemolytic anemia.
The occlusion of
blood vessels may also trap platelets, and their trapping
leads to further blood vessel occlusion and formation of clot.
This
Process Is Easier to Prevent Than to Reverse
Obviously, once
there is extensive occlusion of blood vessels, with severe
damage to extensive kidney tissue, little can be done to reverse
the process.
The key is early
treatment, which in turn depends on early recognition.
Kidney disease
is generally limited to patients who have diffuse scleroderma-that
is, scleroderma with extensive skin disease, rather than patients
with limited scleroderma (CREST syndrome).
Patients with rapidly
progressive skin disease, and those with certain types of
autoantibodies (anti-RNA polymerase antibodies), appear to
be at greater risk.
Check
Your Blood Pressure Often
 |
| Figure 1. Urine dipsticks
for measuring protein levels in urine. |
One way to help
detect kidney disease early is to have all patients with diffuse
scleroderma monitor their blood pressure on a regular basis,
several times a week, so that the earliest kidney involvement
can be detected. Approximately 10 percent of patients who
develop kidney disease do not, for some reason, develop high
blood pressure, so patients may be asked to monitor their
urine for protein.
Both of these approaches
help detect kidney disease before the patient develops the
serious symptoms of kidney and heart failure.
Treat Symptoms Promptly with
ACE Inhibitors
When any persistent
rise in blood pressure is detected, or if there is the appearance
of protein in the urine or the blood changes noted above,
treatment should promptly be instituted with angiotensin converting
enzyme (ACE) inhibitors.
This class of drugs,
which includes such agents as enalapril, captopril, and lisinopril,
among others, has clearly been effective in aborting the devastating
consequences of renal crisis in patients where treatment is
initiated before the kidneys begin to fail.
There is another
group of drugs, called angtiotensin receptor antagonists,
that may also be effective in treating renal crisis, but it
appears they are less effective than ACE inhibitors.
Other classes of
drugs have, over the years, proven to be ineffective.
The lower incidence
of renal crisis that most scleroderma centers are seeing is
attributed to early aggressive treatment of mild to modest
elevations of blood pressure, which abort the development
of the full spectrum of kidney problems. In the past as many
as 30% of patients with diffuse scleroderma developed kidney
disease, whereas the number is much closer to 10 or 15% today.
The
Sooner Treatment Starts, the Better the Results
 |
| Figure 2. How a normal
kidney functions. |
The effectiveness
of treatment for renal crisis depends on whether there is
impairment of kidney function is at the time treatment is
initiated.
Patients who are
treated before the serum creatinine doubles, that is, before
there is a 50% decline in kidney function, tend to have excellent
outcomes.
However, even in
patients whose kidney function declines to the point of their
needing dialysis, treatment with angiotensin converting enzyme
(ACE) inhibitors is effective. Thirty to forty percent of
such patients recover enough renal function so that dialysis
is no longer necessary, and some return to near-normal levels
of kidney function.
Kidney
Disease in Scleroderma Is Best Managed by Experts
The need for aggressive
therapy with angiotensin converting enzyme (ACE) inhibitors,
both in earlier and later stages of kidney disease, cannot
be over-emphasized.
Often, when ACE
inhibitors are first initiated, kidney function continues
to decline and this decline is wrongly attributed to the drug.
Almost always, it is a mistake to stop ACE inhibitors and
to try treating with alternative agents.
Management of kidney
disease in scleroderma is best undertaken by those experienced
with this manifestation and familiar with its clinical course
and response.
Renal
Scleroderma:More Widespread Than Previously Realized?
 |
| Figure 3. Scleroderma
patients at risk for renal crisis should check their blood
pressure several times a week. |
Some recent studies
suggest that kidney involvement in scleroderma may be more
widespread than appreciated.
There may be some
level of abnormal kidney function in many patients with scleroderma,
detectable by assessing the ability of the kidneys to concentrate
the urine or by other soph-isticated kidney function tests.
It is not clear
whether such patients are at greater risk for developing scleroderma
renal crisis. This population could be targeted for closer
monitoring. Future studies should help elucidate this point.
Renal
Scleroderma Is Treatable
The point to remember
is that kidney disease in scleroderma is treatable. The key
to success is early detection and aggressive therapy with
appropriate drugs.
Because kidney disease
is often abrupt in onset and can be devastating in its manifestations,
the physician and patient need to be partners in monitoring
for kidney involvement. |
