Lupus And Me: Kidney Disease And Lupus- 2 Articles

Kidney Disease and Lupus
From: Lupus.org

The two medical terms for the kidney disease that occurs in systemic lupus erythematosus are lupus nephritis or lupus glomerulonephritis. It is estimated that about one-third of people with lupus will develop nephritis that requires medical evaluation and treatment. Lupus nephritis is an important and potentially serious symptom of lupus.

Clinical Course Of Lupus Nephritis

There are very few signs or symptoms of lupus nephritis.

It does not cause pain in the abdomen or back.
However, when protein leaks from the kidneys, it is eliminated from the body in the urine
Foamy, frothy urine and getting up to urinate during the night can suggest excessive protein loss.

The loss of protein in the urine from lupus nephritis may then lead to fluid retention with weight gain and swelling (edema). This is often the first symptom noticed of lupus nephritis.

The edema generally appears as puffiness in the feet, ankles and legs.
This swelling will be absent in the morning, but will gradually worsen as the person walks about during the day.

The clinical path of lupus nephritis is highly variable.

1) Often the signs of lupus nephritis are seen only in urine studies.

· In many people, the urine abnormalities are very mild and may be present during one examination and absent the next.

· This form of lupus nephritis is rather common and generally does not require any special medical evaluation or treatment.

2) In some people, though, abnormal findings in the urine studies may persist or even worsen over time.

· People with this type of lupus nephritis are at risk for loss of kidney function.

· These individuals will need additional studies to assess the extent of their lupus nephritis and to determine the best treatment for controlling the disease.

It is important to recognize that not all kidney problems in people with lupus are due to lupus nephritis.

Infections of the urinary tract, with burning on urination, are quite common in people with lupus and require antibiotic treatment.
Also, signs or symptoms of kidney disease that can be confused with lupus nephritis may be caused by some medications used in lupus treatment. These problems usually go away when the medications are discontinued. Two medications that can cause fluid retention or loss of kidney function are:

-Salicylate compounds (e.g., aspirin)
- non-steroidal anti-inflammatory drugs (NSAIDs)

Studies To Evaluate Lupus Nephritis

There are a number of studies that can be done to test for kidney disease in a person with lupus:

1) Urinalysis

A urinalysis is by far the simplest and most commonly used study to test for lupus nephritis. In this test, a urine sample is examined for the presence of protein and blood cells which are not normally found in the urine.

The blood cells that may collect in the kidney to form and be excreted in the urine are called casts. Casts are seen when the urine is examined under the microscope.
The presence of protein in the urine is called proteinuria.
The presence of red blood cells in the urine is called hematuria
The presence of white blood cells in the urine is called leukocyturia.
The presence of any of these in the urine suggest the possibility of lupus nephritis and generally indicate the need for further studies.

2) Blood work

The main function of the kidney is to remove waste products and excess fluids from the body. Blood studies can be done to measure whether the kidney is doing this job properly.

Two studies that are done to indicate whether waste products are being adequately removed by the kidney and not building up in the blood:
-the blood urea nitrogen (BUN) study
-the serum creatinine study.
Losing protein in the urine may lead to lower levels of protein in the blood. This is measured by:
- the serum albumin study.
Imbalances of salt and water in the blood are detected by chemistry studies such as:
- the serum sodium study
- the potassium study
- the bicarbonate study.
Blood tests may also be done to detect immune system abnormalities that are commonly seen with lupus nephritis. Two commonly used blood tests are:
- the serum complement test, which measures the levels of proteins in the blood that typically are low in lupus nephritis, and
- the antibodies to DNA test which measures these antibodies that typically are high in lupus nephritis.

3) 24-Hour urine collection

Studies of the urine collected by the patient over a 24-hour period determine whether the kidneys are working properly.

These studies measure the kidneys' ability to filter waste products:
-the creatinine clearance test
-the exact amount of protein lost in the urine over a 24-hour period.

4) Imaging studies

There are two ways to examine size and shape of the kidneys, which must be done before a kidney biopsy to help guide the physician doing the biopsy:

an intravenous pyelogram (IVP) involves an injection of dye that collects in the kidneys. An x-ray of the abdomen is then taken which shows the outline of the kidneys.
a sonogram uses soundwaves transmitted through the body to show the shape and size of the surfaces of the kidney.

5) Kidney biopsy

If urine or blood studies suggest lupus nephritis, a kidney biopsy may be performed. The biopsy is done to:

confirm the diagnosis of lupus nephritis
to determine the extent and severity of kidney disease.

A kidney biopsy is done in a hospital by inserting a narrow needle through the skin of the back and removing a small piece of the kidney. (On rare occasions, a kidney biopsy may need to be done surgically in the operating room.)

The specimen of kidney tissue is then examined under a microscope to determine how much inflammation or permanent damage (scarring) is present. These findings classify the type of lupus nephritis by using a scoring system devised by the World Health Organization (WHO) (see Table 1). Knowing the type of lupus nephritis helps to determine the seriousness of the nephritis and the best approach to treatment.

World Health Organization (WHO) Classification System for Lupus Nephritis

The World Health Organization has established a classification system for types of lupus nephritis, which are described in the table below.

Table 1. World Health Organization (WHO) Classification System for Lupus Nephritis

Class	Designation	Comment
I	Normal	No evidence of lupus nephritis on the kidney biopsy.
II	Mesangial Nephritis	Most mild form of lupus nephritis; typically responds completely to treatment with corticosteroids.
III	Focal Proliferative Nephritis	Very early stage of more advanced lupus nephritis; typically treated with high doses of corticosteroids, with excellent outcome.
IV	Diffuse Proliferative Nephritis	Advanced stage of lupus nephritis with definite risk of loss of kidney function; typically treated with high doses of corticosteriods combined with immunosuppressive drugs.
V	Lupus Membranous Nephropathy	Generally associated with excessive protein loss and edema; typically treated with high doses of corticosteroids, with or without immunosuppressive drugs.

Treatment and Therapy

Treatment for lupus nephritis must be individualized to the needs of the specific person. All of the following must be taken into consideration:

the amount of edema (swelling)
urine abnormalities
amount of protein in the urine
reduction of kidney function
findings of the kidney biopsy.

Diuretic agents may be used to help eliminate excess fluid. Anti-hypertensive drugs can control increased blood pressure. Anticoagulation drugs are used in case of complications arising from blood clots. Changes in the diet can be made to control the intake of salt, proteins, and calories.

There are two major forms of drug therapy used for lupus nephritis: corticosteroids to control inflammation, and cytotoxic or immunosuppressive drugs to suppress the activity of the immune system.

Corticosteroids

Corticosteroids have been used to manage lupus nephritis for nearly forty years. Still, there are many unanswered questions as to exactly how they work and how they may be most effectively used.

High doses of corticosteroids, or even corticosteroids given for extended periods of time, may cause a number of side effects (some side effects can be lessened by a low calorie and low salt diet):

- increased appetite
- fluid retention with weight gain
- puffy face
- easy bruising
- moodiness
- loss of mineral from the bones
- cataracts
- thinning hair
- an increased risk of infection and diabetes.

High doses of corticosteroids (taken orally or intravenously) are given until the lupus nephritis improves.
The dose of corticosteroids is then slowly reduced under close watch of a physician to make certain that the nephritis doesn't worsen.

Cytotoxic or immunosuppressive drugs are generally regarded as standard treatment for people with serious lupus nephritis. These drugs block the function of the immune system, which in turn prevents further damage to the kidneys.

The most commonly used is cyclophosphamide (Cytoxan).

Immunosuppressives that are used less frequently include: azathioprine (Imuran), chlorambucil (Leukeran), and cyclosporine (Sandimmune or Neoral).

The application of these drugs typically varies according to classification:

Corticosteroids (such as prednisone, prednisolone and methylprednisolone, or Medrol) are considered necessary in the initial treatment in virtually all forms of lupus nephritis.
Corticosteroids are the only type of drug required for those with Class II (mesangial nephritis).
A combination of corticosteroids and immunosuppressives are used to treat most people with Class III (focal proliferative nephritis), Class IV (diffuse proliferative nephritis) or advanced Class V (membranous nephropathy).

Several promising experimental therapies for lupus nephritis are currently being studied. These include:

newer immunosuppressive drugs like cyclosporine and mycophenolate mofetil (CellCept)
the removal of antibodies associated with lupus nephritis by selective plasmapheresis
the administration of biologic agents that suppress the immune system.

Kidney Failure

Despite the prescribed treatment, some people with lupus nephritis do have progressive loss of kidney function. In the case of complete failure of both kidneys, dialysis, and eventually kidney transplantation will be required.

Dialysis can be done in two ways:

Hemodialysis passes the blood through a dialysis machine and filters it directly.
Peritoneal dialysis places fluid in the abdominal cavity and subsequently removes it.

Kidney transplantation has been very successful in people who have had kidney failure from lupus nephritis. Usually they are kept on artificial dialysis until there is little or no evidence of active lupus before the transplantation procedure is performed. Afterwards, immunosuppressive drugs will be used to prevent rejection of the transplanted kidney.

Conclusion

Over the past several decades, there have been major advances in the understanding of what causes lupus nephritis and, in particular, improvements in treatment. Today, more than 80 percent of people with lupus nephritis will live a normal life span.

Related Information

On this web site
NSAIDs
Steroids
Immune Suppressing Drugs
Medications

On the Internet
MedlinePlus: Drug Information
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
NIDDK: Kidney Disease and Kidney Failure
NIDDK: Hematuria
NIDDK: Kidney Biopsy
NIDDK: Proteinuria
NIDDK: Your Kidneys and How They Work

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Lupus and Kidney Disease: What You Should Know about Lupus Nephritis (Lupus Kidney Disease)

From: http://www.hss.edu/conditions_lupus-nephritis-kidney-disease.asp

Background Information

Lupus:
Lupus is a chronic and autoimmune disease that affects several parts of the body, including joints, blood, skin, and kidneys. The immune system of those with lupus does not function properly. Lupus creates autoantibodies that fight and damage the cells, tissues, and body organs. When they are present, they can likely lead to disease.

Kidney:
The kidney is a bean-shaped, fist-sized organ that helps cleans the body from any toxic or other waste products. In addition, the kidney plays an important role in helping to maintain blood pressure, the volume of body fluids, and the body's water and PH balance. We have two kidneys, but one healthy kidney could be sufficient for our needs. As we get older, we start to lose some of our kidney function.

Lupus Nephritis

Lupus Nephritis (LN) is the disease of the kidneys due to lupus. This occurs when lupus autoantibodies deposit in the kidneys and cause inflammation. About 30-50% of lupus patients will develop LN within the first six months to three years of being diagnosed with SLE. Inflammation of the kidney prevents it from functioning normally and can cause it to spill protein, which causes frothy and/or bloody urine. Other early manifestations of lupus nephritis include swelling of the feet and an increase in blood pressure. These symptoms are usually seen as the first signs of the disease.

Signs of LN may include:

· Swelling or puffiness of feet, legs, eyes

· High blood pressure

· Frothy urine or getting up constantly to urinate at night

· Blood in urine

One may not experience any symptoms, however, so a urine test is needed. It’s crucial to have your doctor rule out other causes such as kidney stones or a urinary infection before considering the diagnosis of LN.

WHO (World Health Organization) Lupus Nephritis Classification:

Class 1: Minimal Mesangial Lupus nephritis (LN)
Class 2: Mesangial Proliferative LN
Class 3: Focal Proliferative LN
Class 4: Diffuse Proliferative LN
Class 5: Membranous LN

Kidney biopsy is crucial to help diagnose lupus nephritis and rule out other issues. It’s also helpful to identify the class of LN in a given case in order to determine the most effective therapy for that patient.

A biopsy is performed whenever there’s an indication of a severe form of nephritis (Class 3-5). At times, especially when the disease does not respond well to therapy or there is a new flare, the biopsy will need to be repeated to assess intensity of inflammation and degree of scarring. If scarring is the main finding of the biopsy (often classified as class VI or Advanced sclerosing LN according to more recent classification systems), aggressive therapy is unlikely to be helpful and may need to be discontinued in order to avoid unnecessary toxicity.

Testing for Lupus Nephritis

There is a wide range of tests that can determine how the kidney is affected.

1. Blood: BUN (normally<20) and creatinine (Cr; normally <1 in average woman; it may be higher in muscular men as it reflects muscle mass). Also albumin (normal>3.5) which may be decreased due to loss of protein in the urine.

2. Electrolytes: sodium, potassium, bicarbonate

3. Creatinine clearance: Calculated by using creatinine, age, race, gender. Normally 80-120 ml/min/1.73m2

4. Urine analysis: Normally 0-trace protein, no red and white blood cells (<5 RBC, <5 WBC)

5. 24-h urine protein: (creatinine is also measured to assess whether collection was performed properly): normally <300mg/24h. In lupus by definition>500 mg/24h.

6. Spot urine protein/creatinine ratio: Normally <300 mg/24h. It may vary depending on the timing of collection: best to test second urine of the day

7. Renal ultrasound: size of kidneys and consistency of kidney tissue

8. Kidney biopsy

Other Important Tests:

1. Serology:

1. C3 (normally>80), when disease is active, it is usually low

2. C4 (normally>18), when disease is active, it is usually low

3. Anti-dsDNA (normal is 0), when disease is active, it is usually high

4. Antiphospolipid antibodies (anticardiolipin antibodies IgG, IgM, IgA, and lupus anticoagulant). This might determine whether blood thinners are needed

2. Bone tests:

1. Blood level of 25-OH-Vitamin D (normal >30 ng/ml)

2. Blood level of intact parathyroid hormone (iPTH; it is usually high in advanced kidney disease or with low 25-OH-Vitamin D levels)

3. Bone mineral density test (to check for osteoporosis)

3. Fasting lipids: High in nephrotic syndrome

4. Fasting blood sugar: Diabetes or other complications of steroids

5. Hemoglobin (HB): Anemia might be due to the inflammation, blood loss, hemolysis, or advanced kidney disease.

6. White blood cells: Low due to the disease or therapy. Increased risk of infection.

7. Platelets (PLT): Low due to the disease or therapy. Increased risk of bleeding.

8. Purified protein derivative (PPD) test for latent tuberculosis (TB)

9. Hepatitis C, Hepatitis B, HIV

Therapy of Lupus Nephritis

In proliferative lupus nephritis (severe class III or class IV), aggressive immunosuppressive therapy is required without delay to “calm down” the overactive immune system. This is called induction therapy, as it aims to induce remission. There are many types of induction therapy, but typically all require a high dose of glucocorticoids (such as Medrol or Prednisone) plus one of the following:

1. Chemotherapy (IV cyclophosphamide every month for six months)

2. Oral Cellcept (mycophenolic acid)

After about six months of induction therapy and hopefully a good response or remission of the disease, we apply maintenance of remission therapy to maintain remission and avoid a new flare of the nephritis. In this case we typically use only a low dose of glucocorticoids, or none at all, plus one of the following options:

1. Oral Cellcept (mycophenolic acid)

2. Oral Imuran (azathioprine)

For both induction and maintenance therapies, patients may consider enrolling in clinical trials of new promising therapeutic agents. This is a consideration since available conventional therapies at present are not optimal with regard to either efficacy or safety.

Addressing Comorbidity (associated health issues)

Although induction therapy and maintenance of remission therapy comprise the main strategy we use to suppress kidney inflammation in patients with lupus nephritis, additional therapies are needed for optimal results:

1. Antihypertensives: These are needed to control the often very high blood pressure of these patients as a result of LN:

1. Angiotensin Converting Enzyme inhibitors (ACEI)

2. Angiotensin Receptor Blocker (ARB)

3. Diuretics (Lasix)
Note: ACEI and ARB agents are also effective in decreasing the amount of protein spilled in the urine, independently of the immunosuppressive therapies indicated above.

2. Bone Protection: The following agents are needed to protect the bones from osteoporosis and fractures that may occur as an adverse event from therapy with glucocorticoids.

1. Calcium (about 1500 mg of calcium per day) + Vitamin D3 (at least 1000 units per day; higher doses may be required if the blood test shows a low level).

2. Bisphosphonates (Fosamax, Actonel, Boniva, etc.), if there are no contraindications to their use. In some cases with severe osteoporosis, doctors would use Forteo (teriparatide, a form of parathyroid hormone).

3. Lipid Reduction: These agents are often needed to protect from atherosclerosis and its consequences (heart attack, stroke, etc.) in the long term.
a. Statins are usually used (if there are no contraindications).

4. Anticoagulation agents are used when there is a high risk of blood clots as it might occur in the antiphospholipid and nephrotic syndromes

5. Vaccines such those below with antigens from inactivated infectious agents are used to protect from infections while the immune system is suppressed with LN therapy. Please note that vaccines with live viruses (such as the MMR, oral polio, shingles, nasal influenza vaccine preparations) are contraindicated when the immune system is suppressed.

1. Influenza

2. Pneumonia

Some lifestyle changes that can be very important in protecting the kidneys include:

· Being hydrated

· Maintaining a low sodium intake, especially if one has hypertension

· Maintaining a low potassium intake, low phosphorus, low protein (for patients with already diminished kidney function)

· Maintaining a low cholesterol diet

· Don’t smoke or drink alcohol

· Exercise

· Maintain your blood pressure and weight

· Avoid nephrotoxic agents such as NSAIDS (Advil, Aleve) and so forth.

Conclusion and Important Take-Home Messages

· Be active in your health care and partner with your rheumatologist and nephrologists (doctor who specialize in kidney diseases)

· Be aware of what pills you’re taking, their dosage, and when to take them.

· Recognize the different signs of flares relating to the disease, such as headache, high blood pressure, discolored urine, fever, joint pains, skin rash, shortness of breath, and foot/eye swelling. Notify your doctors.

· Recognize the signs of potential drug adverse events such as fever, chills, sore throat, cough, shortness of breath, blood in urine and diarrhea. Notify your doctors.

· Do not ignore your bone health (having enough calcium/vitamin D) or cardiovascular health (i.e., smoking, low cholesterol diet)