Renal Scleroderma

By 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)

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.