The Lupus Book: A Guide for Patients and Their Families, Third Edition (28 page)

alterations of therapy if needed.

ARE THERE OTHER FORMS OF LUPUS KIDNEY DISEASE

BESIDES GLOMERULONEPHRITIS?

Although they rarely cause symptoms, many
commonly used drugs can affect

renal function
, the most common of which are the NSAIDs. Some of them,

particularly indomethacin, can raise serum creatinine as part of their action

against a chemical called prostaglandin. A normal serum creatinine is up to

about 1.3 mg/dL. If the creatinine is slightly above this level, nonsteroidals

should probably be used only for a few days and the blood should be carefully

monitored. Circumstances when this might arise would be an acute attack of

gout or bursitis. Since creatinines are measured in terms of a logarithmic function rather than an arithmetic one, a serum creatinine of 2 indicates only 50

percent kidney function, 3 means 30 percent kidney function, and 4 signifies 20

percent kidney function. (Remember logarithms from high school? A rise in

creatinine from 2 to 3 indicates a 10-fold change!) Patients with a serum cre-

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atinine above 6 mg/dL usually require dialysis. The use of NSAIDs is not ad-

vised if the creatinine is above 2.

Other drugs can induce an
interstitial nephritis
, which inflames and then scars the connective tissue of the glomerulus. Certain antibiotics and anti-inflammatory drugs are included in this group. Sjo¨gren’s syndrome is associated with
tubular dysfunction
, which leads to electrolyte abnormalities. High blood pressure also damages kidney tissue and is capable of inducing renal failure

regardless of SLE activity. Patients with antiphospholipid antibodies are predisposed toward developing
renal vein thrombosis
, especially if they have membranous nephritis. This condition can result in acute renal failure, flank (side of the back) pain, and fever. It is managed with anticoagulation and steroids if the lupus is active.

WHAT IS THE NATURAL COURSE OF LUPUS NEPHRITIS

AND HOW DO WE TREAT IT?

When Dr. Cohn told Gillian she had lupus in her kidney, it was not an

easy thing to say to a promising concert pianist. At the time, her ankles

were so swollen that Gillian couldn’t wear any shoes other than an old pair

of sneakers. Her anti-DNA levels were high and serum complement levels

low. Dr. Cohn arranged for a kidney biopsy, which showed class IV (dif-

fuse proliferative) disease with a lot of activity and little scarring. He told Gillian that she had a reversible lesion and needed chemotherapy as well

as steroids. She was started on 60 mg of prednisone a day and received

six monthly doses of intravenous Cytoxan at the hospital infusion center

as an outpatient. During this time, Gillian gained 40 pounds, became moody

and irritable, and could not concentrate on her practicing. After 6 months,

she began to improve. Her creatinine was still normal at 1.4 and her 24-

hour urine protein had decreased from 7 grams to 3. At this point, Dr.

Cohn extended the Cytoxan treatments to every 3 months and tapered her

prednisone to 10 mg a day. Gillian did well for a year, but her blood

pressure began to go up, as did her cholesterol and blood sugars. She was

started on blood pressure medicine and put on a strict low-fat, low-

carbohydrate diet. After 2 years, the Cytoxan was stopped. Gillian was

maintained on 10 mg of prednisone a day to suppress her renal disease and

her mild lupus symptoms outside the kidney. Five years later, her creatinine

was 2.6, along with a 24-hour urine protein of 1.3 grams. Dr. Cohn ar-

ranged for a second biopsy that showed little lupus nephritis activity but a

lot of damage from hypertension and scarring. Her medicine was kept the

same. Being on the road a lot, Gillian tried the best she could to keep to

her diet, but it was not easy. After 10 years of nephritis, Gillian’s creatinine finally crept up near 7 and she was placed on hemodialysis. Fortunately,

her brother was able to donate a kidney and she underwent a successful

transplant. Fifteen years later, her creatinine is 1.0 and she is on 10 mg of

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Where and How Can the Body Be Affected by Lupus?

prednisone a day, cell cept, Cyclosporin A to prevent transplant rejection,

a diabetes medicine, a cholesterol medicine, and a blood pressure medicine.

At age 30, Gillian teaches music at a junior college.

Patients with class I and II biopsy patterns have an excellent outcome. Class

V is relatively resistant to therapy even though most rheumatologists try a course of corticosteroids with or without
immunosuppressive regimens
. Some of the drugs that fall into this category include azathioprine, cyclophosphamide, mycophenolate mofetil, or cyclosporin A, all of which are discussed in Chapters

27 and 28. Class VI usually leads to end-stage renal disease within months and

no specific therapy is indicated. Class III or IV proliferative nephritis is reversible some of the time with aggressive therapy. High doses of corticosteroids

with or without immunosuppressives (particularly intravenous cyclophospha-

mide, or Cytoxan) can prolong kidney function and prevent the need for dialysis over a 10-year period in half the patients. (See Chapter 28.)

Is there anything you can do to prevent the effects of kidney disease? High

blood pressure should be managed aggressively, since it accelerates functional

kidney impairment. Stress reduction helps lower blood pressure. Patients with

renal disease should restrict their salt intake to no more than 3 grams a day;

when renal function is 50 percent or less, normal protein intake should also be restricted. Diuretics help remove fluid in lupus patients and make them feel more comfortable, but they must be used cautiously, since they alter electrolyte balance. Potassium supplementation is given to patients with normal kidney func-

tion on most diuretics. However, potassium intake is restricted in patients with markedly impaired renal function.

HOW ARE THE URINARY TRACT AND BLADDER

AFFECTED BY LUPUS?

The ureter is not involved in lupus and the bladder is a rare target of the disease.

But a condition known as
lupus cystitis
is observed in 1 to 5 percent of those with lupus. Manifested by inflammation of the lining of the bladder with blood

in the urine, cystitis can be diagnosed by an office procedure known as cystos-

copy. Lupus cystitis frequently correlates with gastrointestinal malabsorption. It is treated with antibiotics and anti-inflammatory lupus medications. Occasionally, pentosan polysulfate sodium (Elmiron) is prescribed or a drug called

DMSO (dimethylsulfoxide) is administered directly into the bladder.

Young women are especially prone to develop urinary tract infections, and

young women with lupus are particularly vulnerable to infections in general.

The drugs of choice for most urinary tract infections are sulfa antibiotics, but these are often poorly tolerated by SLE patients (Chapter 9). A common problem

I encounter takes place when gynecologists, urologists, or family practitioners
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prescribe sulfa antibiotics without realizing that lupus patients frequently develop flareups of SLE when they are given these drugs. Many antibiotic alter-

natives are available in these circumstances. Always tell physicians who are

treating you that they are dealing with a lupus patient.

THE BOTTOM LINE

Lupus nephritis is very tricky to treat, since it produces few symptoms or signs.

Despite our best efforts, patients may still evolve kidney failure. First, a doctor must confirm that it is indeed lupus that is affecting the kidney. Second, renal function and inflammation must be measured. On the basis of blood tests, urine

testing, and biopsy material (if available), a careful treatment plan is formulated.

Because many of the drugs used to prevent or retard this disease are quite potent in their own right, a careful balance is important.

The reader is referred to other parts of this book for details regarding dialysis and transplantation (Chapter 28); cyclophosphamide, mycophenolate mofetil,

chlorambucil, nitrogen mustard, azathioprine, pulse steroids, steroids, and apheresis management (Chapters 27 and 28); and pregnancy in the patient with lupus

nephritis (Chapter 30).

20

The Blood and Lymphatic Systems

Before rheumatology was recognized as a subspecialty of internal medicine in

1972, lupus patients were treated primarily by another group of subspecialists—

hematologists. Hematology is the study of diseases of the lymph glands and

blood components, all of which play a key role in the well-being of individuals with SLE. This chapter looks at why many lupus patients have blood and lymphatic abnormalities. Although rheumatologists supervise the overall manage-

ment of SLE, hematologists still play an important role in managing the blood

abnormalities seen in lupus.

WHAT’S WRONG WITH THE PATIENT’S BLOOD?

Whole blood is divided into three major components: red blood cells, white

blood cells, and platelets. The function of each of these is reviewed in Chapter 5. In SLE, any or all of these components may be quantitatively (or numerically) high or low, or they may be malfunctioning
qualitatively
. A simple tube of blood measures quantitative values; qualitative tests also require blood samples but are more difficult to perform.

COULD THE PROBLEM BE ANEMIA?

Are you tired? Do you feel weak? Do you look pale? If any of these answers

are yes, you could be anemic. About 80 percent of SLE patients are anemic

during the course of their disease. Anemia, or a low red blood cell count, is

defined as a
hemoglobin
count of less than 12 grams per deciliter (g/dL) or a
hematocrit
of less than 36. The hematocrit is the percentage of red cells per 100

ml of blood and it is usually about three times the hemoglobin. A normal he-

moglobin ranges from 12 to 16 g/dL and indicates the amount of a certain

protein in red blood cells. Anemia in lupus is divided into two general catego-

ries: nonimmunologic and immunologic. The major symptom of anemia is fa-

tigue, which is usually evident when the hemoglobin drops into the 10 g/dL

range. Further decreases can make a person appear pale and feel weak.

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Nonimmunologic Anemias

Red blood cells are made by the bone marrow and released into the circulation.

When people develop chronic inflammatory disorders, the stimulus to make red

blood cells decreases. These individuals develop what is called an
anemia of
chronic disease
.

A week after Sylvia had her annual gynecologic evaluation, her doctor

called her to say that she was anemic. Her hemoglobin was 9.7, and it had

been 13 a year before. Sylvia’s lupus had been under excellent control with

three aspirins four times a day, and even though she felt tired, Sylvia had

only minimal aching. Her periods had always been heavy, but not unusually

so. She consulted her internist, who performed a thorough evaluation. He

found that Sylvia’s anemia stemmed from several causes: she was iron-

deficient due to her heavy periods, had an anemia of chronic disease, and

was also having a problem with the aspirin. An endoscopy of her stomach

showed evidence of gastritis from taking aspirin. Her doctor started her on

iron and omeprazole (an ulcer medicine with the brand name Prilosec) and

stopped aspirin for 6 weeks. When her hemoglobin rose to 12 and another

endoscopy showed the ulcer healing, an aspirin derivative (Disalcid) that

rarely causes ulcers was started and she was kept on the iron.

Lupus patients can be anemic for any of the reasons that makes otherwise healthy people become anemic. However, several of these causes are more prominent in

SLE, especially when superimposed upon a preexisting anemia or chronic disease.

Among young women a common cause is heavy menstrual bleeding and resultant

iron-deficiency anemia
. Another cause of this type of anemia is the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or aspirin,

which can irritate the stomach lining, inducing secondary blood loss from an erosive gastritis. Practitioners often check the stools of their lupus patients for blood on a periodic basis if these patients are taking nonsteroidals. If continued NSAID administration is necessary, patients with these problems are given iron supplements and gastric agents that coat the stomach. However, doctors often discontinue the NSAIDs. Occasionally, anemias in lupus patients respond to the administration of folic acid or injections of vitamin B . Since African Americans have an increased 12

prevalence of SLE, sickle cell anemia and sickle cell traits should be screened for in this population.

A hormone made by the kidney, called
erythropoietin
(EPO), stimulates the bone marrow to make red blood cells.
Chronic renal disease
is associated with decreased EPO levels, which can lead to anemia. The availability of EPO injections has greatly improved these patients’ quality of life over the last decade.

There are many other causes of anemia in lupus, but they occur in the same

proportion as in the general population.

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Where and How Can the Body Be Affected by Lupus?