15 Questions - Kidney Issues with Lupus

1. What are the symptoms of kidney problems associated with Lupus?  Is pain associated with the problem?  Brentwood, MO

The unfortunate problem with Lupus related kidney disorders, as with the case of most kidney problems, is that a patient cannot directly sense a problem with the kidney until a significant amount of his/her renal function is gone. For example, most patients with kidney disease do not experience any symptoms until 70-75% of renal function is gone. When those symptoms do appear, they are often non-specific including reduced appetite, weight loss, and difficulty with concentration. I need to emphasize to the reader that these symptoms apply to all patients with failing kidneys and not specific to Lupus patients. However, there are more closely linked to the onset of Lupus nephritis. About 60% of patients with SLE will develop clinically apparent Lupus nephritis. The clinical manifestations of Lupus nephritis include increased loss of protein in the urine. This loss of protein leads to accumulation of sodium (salt) and water in the peripheral tissues leading to edema. Patients that lose over 3000 mg/24 hrs of protein (normal up to 150 mg/24 hrs) can develop what is called the Nephrotic syndrome; a condition where swelling is found throughout the body including the hands, feet, lower legs and eyelids. For many patient’s, the onset of proteinuria can be detected by patients if they notice that their urine has developed an unusual “foamy” character. The increase in urine foam is sometimes the result of increased urinary protein content.

Other problems with Lupus nephritis is high blood pressure. For many patients, the new development of hypertension precedes the onset of overt Lupus nephritis. Any SLE patient developing hard to control hypertension should see their doctor for possible involvement of Lupus in their kidneys. Lastly to answer your question regarding a “pain” in the kidney associated with SLE, I am afraid not. As I noted previously, we cannot sense “damage” to the kidney until a significant amount of renal function is lost. There are only two notable exceptions to this condition; patients with infection that rises into the kidney can feel flank discomfort if the infection involves the capsule or outer lining of the kidney. Also, patients with the overlapping complications of SLE called the Anti-Cardiolipin or Anti-Phospholipid Antibody syndrome can experience pain in the kidney if a blood clot is formed or lodged in the kidney. I would summarize these comments to say that the development of new onset hypertension, swelling of the feet hands or eyelids and the development of “foamy-Like” urine should alert a patient to see their doctor.
 

2. Are all kidney problems in lupus nephritis problems?

If I understand you correctly, you are asking whether there are any conditions in Lupus nephritis that are benign. That is a complicated question. Let me start by saying that the optimal condition for any SLE patient is to have no manifestations of Lupus Nephritis. Dr. Dan Wallace of UCLA noted that patients with kidney involvement represent a patient with inherently more complicated disease; one that requires more attention from their physician and often higher levels of immunosuppression. All kidney disease can have significant impact on a patient’s overall health including increasing the risk for coronary disease and cardiovascular complications. With that as background, there are forms of Lupus nephritis that pose little risk for progression to end-stage renal disease. For example, Class IIa mesangial Lupus nephritis exhibits hematuria (blood in the urine) and proteinuria, but has a small chance of progressing to dialysis. However, about 30-40% of patients with Class IIa Lupus nephritis will progress to Class III/IV Lupus nephritis. These two forms are significantly more aggressive and associated with a higher risk of dialysis and more potentially life-threatening complications of SLE.

3. What factors might pre-dispose a person to kidney damage?
I am guessing that you are asking what characteristics of Lupus pre-dispose a patient to lupus nephritis. Well that is a really good question. Clearly, the main determinates are your genetic background. If you have a relative with SLE that involves the kidney then it is more likely that you will also have renal involvement. The apparent random process of when auto antibodies like Anti-ds-DNA “cross react” with normal structures in the kidney (a process called molecular mimicry) and induce inflammation are risk factors, but currently we do not have the technology to identify those patients. Other more general factors include hypertension and the amount of protein in a patient’s urine. The more protein a patient has the more likely they are to experience kidney damage over time.

4. When is it necessary for doctors to do a renal biopsy?

In an SLE patient with no prior history of Lupus nephritis and a normal urinalysis, a kidney biopsy is not required. However, previous studies have clearly shown that there is no ability of a doctor to predict whether a patient has a mild or aggressive form of nephritis based upon the number of red blood cells in the urine or the amount of protein. For example, patients with Class IV nephritis (the most aggressive and likely to progress to dialysis) often will have less proteinuria than a patient with Class V. Thus when a person should get a kidney biopsy is still based upon your doctors judgment, but it should be emphasized that your doctor cannot rule out significant renal disease by the amount of proteinuria and hematuria. Prospective studies on this question have also given very helpful insights. For example, studies of patients with specific findings on the biopsy like the presence of crescents clearly are at higher risk for progressive disease. Moreover, other studies have shown that if a patient continues to exhibit crescents after intensive immunosuppression they have a very high likelihood of progression to dialysis. In my personal practice, my threshold for biopsying patients is low. The current safety of kidney biopsies and reduced patient discomfort have enabled nephrologist to use serial biopsies as a tool for very precise patient management. As a general comment, patients with chronic kidney disease (manifested by elevated serum creatinine), hematuria or proteinuria over 500 mg/24 hrs should have a defining biopsy as part of their diagnosis and disease management. 

5. What are the lab values of Lupus most closely associated with later renal failure?  Is there a lab value profile of Lupus patients who are most likely to have renal involvement?   How do you know if you are higher risk or lower risk for renal involvement?  I have read some subtypes are low risk.  Charlotte, NC

Yes there are very clearly certain lab values that are clues to the potential for significant kidney involvement. For example, the serum creatinine is a routine laboratory value that your doctor should be checking on you every 3-6 months. The serum creatinine (Cr) is a blood number that reflects the ability of the kidney to clear toxins from the body. Thus, patients with a higher serum Cr have lower kidney function. The interpretation of this test can be subtle. For example, a young, petite woman who weighs 110lbs may have a normal Cr of 0.6 mg/dl.  If her Cr rises to 1.0 mg/dl that will remain within the “normal range” but clearly may not be normal for her. In a woman of that size, this rise in Cr represents a 40% reduction in kidney function; a very significant drop. To continue the example, if this patient also had hematuria (red cells in the urine) or proteinuria, I would strongly consider a kidney biopsy to rule out the possibility of evolving lupus nephritis. Other tests that correlate with Lupus nephritis involve patients that go onto develop Nephrotic syndrome. This is a condition where the involvement of Lupus in the kidney is of sufficient severity that the patient is loosing over 3000 mg of protein/24 hours. In nephrotic syndrome, the serum albumin level will fall below 4.0 mg/dl. This is may indicate that the protein losses in the urine are severe and by extension most likely represents significant Lupus nephritis. Patients with the nephrotic syndrome also have markedly elevated serum Cholesterol. For the SLE patient with a reasonable diet, the onset of very high cholesterol can represent the presence of the nephrotic syndrome and significant Lupus nephritis. Dr. James Balow and his team at the NIH have shown that serum hematocrit (red blood cell mass in the blood) less than 26% is the most predictive for progressive renal disease. Patients with the more aggressive forms of Lupus nephritis including Class III, IV, Vc and Vd, the serum compliment levels C3, C4 and CH50 levels will fall. Lastly, prospective studies have shown that higher levels of antibodies recognizing double stranded DNA roughly correlate with more aggressive forms of Lupus nephritis. I need to emphasize that no single test is able to accurately predict which patient may have benign or proliferative forms of Lupus nephritis. When all these above tests are tracked by an experienced doctor, an accurate and timely management of a patient is clearly possible.  These tests are currently the most predictive of underlying Lupus nephritis and should be thoroughly investigated. 

In response to the last portion of your question, there are forms of Lupus nephritis that are less aggressive. Please see the answer to question #2 for more details.

6. I am 50 yr. old and I was diagnosed with Lupus about three years ago.  I get constant urinary tract infections (about every three months).  I have noticed that each time they are taking longer to clear up.  Do constant UTIs cause kidney damage and should I be concerned?  My only medication is plaquenil.  Miami, FL

Your question is a common and I thank you for asking it. Yes, patients with SLE have up to a 4-fold greater risk of developing UTIs. These UTIs are also more likely to become complicated and lead to more significant infections. Risk factors for the development of a UTI in an SLE patient are similar to other populations and include - Age, duration of SLE and the use of immunosuppressive medications. The most common organism was E-Coli. Other variables to consider include the observation that a person has repeated “UTIs” in the absence of positive urine cultures, you have to worry about Lupus nephritis with a strong “interstitial” component. Lupus autoimmunity is not limited to the glomerulus of the kidney but can also involve the tubules or interstitium of the kidney. When this happens it can look very much like a “sterile” UTI. You could consult your doctor if your UTIs are repeatedly culture negative

7. My doctor is concerned that my switch to estrogen birth control could increase the risk of having a flare up. My nephritis is in remission and I switched off Depo-Provera because of irregular bleeding, but I'm really freaked out that being on estrogen will cause a flare with the lupus nephritis. Do I need to be concerned? Culver City, CA

Your question is common. A recent prospective study of 351 patients with SLE examined the rate of Lupus flares in patients receiving supplemental estrogens and those receiving placebo. In this very elegant study, the authors found no difference in severe flare rates, while there were small increases in mild to moderate flares. The probability of ANY flare was 0.64 for women on estrogens versus 0.51 for placebo. While this difference was significant it also illustrates and very important observation; namely, that overall flare rates in SLE are low. In patients with significant renal disease, prospective studies have shown a flare rate of approximately 30% at 30 months. With regard to blood clots (deep venous thrombosis), there was no significant increased rate of thrombosis. It is important to emphasize to the readers that these findings cannot be uniformly applied to all patients with SLE. There are patients for whom administration of oral estrogens may not be wise. For example, patients with the Nephrotic syndrome in which the kidney looses large amounts of protein in the urine, there is a relative increased risk for blood clots due to the loss of specific “anti-clotting” proteins. Likewise, patients with the associated disorder of the Anti-Cardiolipin Antibody or the Lupus Anti-Phospholipid antibody syndrome are both at increased for blood clots and thus should be avoided.  The ultimate decision for whether to administer estrogens or not to a Lupus patient will depend upon the indications for administering the estrogens; e.g. severe hot flashes, broad mood swings, depression, severe osteoporosis and the risk of  a lupus flare. The data clearly indicates that a short term course of estrogens can be safely administered. I strongly suggest you discuss this with your doctor and assist them in identifying your specific risk factors.

8. My daughter had a kidney transplant in 1992 and has not experienced any symptoms of Lupus since. Does every Lupus patient experience this same outcome or is this an unusual case. The donor was her living sister, who was 22 at the time.   She still takes 5 mgs of Prednisone, as her doctors are apprehensive about eliminating it completely.   Lake Suzy, FL

First of all let me say that I am quite pleased for your daughter. Good for her. As to your question, it is well described that a patient with end stage renal disease (ESRD) from Lupus nephritis and has received a kidney transplant, typically ceases to demonstrate any symptoms of SLE. For over 95% of patients, they experience a complete remission. Some clinical investigators have argued that the absence of symptoms is because of the necessary immunosuppressive drugs that are routine following transplantation. While this may be true, there are many patients like your daughter who are on relatively minimal immunosuppression who continue to do well. Moreover, many patients with end stage renal disease from Lupus who do not receive a transplant also experience a complete remission. A couple of other comments regarding transplantation in SLE; current registry studies from Johns Hopkins and other transplant centers find no reduction in the overall life of a transplanted kidney.  Just as lupus flairs are rare with ESRD, the recurrence of Lupus nephritis in a transplanted kidney is also unusual, but it does occur.

9. Is an annual cystology necessary follow-up after taking Cytoxan?  I have Class III Lupus Nephritis and underwent an 18 month course of Cytoxan 10 years ago with good results.  Just recently, I read that anyone who has taken Cytoxan should have an annual cystology (I don't know what that is) to check for bladder cancer, but none of my doctors have ever said anything about any kind of follow-up and have never done anything more than routine blood work and urinalyses to monitor kidney function.  Should I be worried about bladder cancer?  Should I insist on an annual cystology?  Escondido, CA

Very good question. Intravenous Cytoxan is metabolized by the liver and generates a metabolite that can be quite toxic to the lining of the bladder. This is why patients need to be vigorously hydrated prior to and after an infusion of Cytoxan. The true incidence of Cytoxan induced bladder cancer in SLE patients is unknown. In patients with a similar disease Wegener’s granulomatosis, the incidence is approximately 10% after 16 years. It should be noted however, that Wegener’s patients are often treated with oral Cytoxan. There is general agreement that administering Cytoxan intravenously can lower the risk of bladder cancer. With that as background, I do believe that regular (every 6 months) urine cytologies is a reasonable and important aspect of your overall care.

10. What is the likelihood of a successful pregnancy in patients with lupus and kidney issues and who have never had children before?  Bellevue, WA

The statistics for successful pregnancies in SLE patients has improved over the years. Currently, over 50% of pregnancies are carried to term with no difficulties. Moreover, approximately 25% of Lupus patients will experience pre-term delivery, but without significant complications to the child. Risk factors for an unsuccessful pregnancy include the presence of the Lupus Anti-phospholipid Antibody syndrome. In this condition, patients develop and auto-antibody that leads to a hypercogaulable state.  This results in placental ischemia leading to abruption placentae, pre-eclampsia and fetal loss. If a patient with Lupus has some degree of renal failure, the good news is that if their serum creatinine is less than 2.0 mg/dl there is approximately a 10% chance of progression of their renal insufficiency over the course of the pregnancy.

11. I've been diagnose with lupus since 1996.  My creatine has now reached 3.0 and my doctor has advised me to have low protein intake of food.   What is the best diet for this?  How much daily protein in my diet is acceptable?   Manila, Philippines

Low protein diets have not shown to be effective in slowing the progression of renal disease. In a large study of over 800 patients (MDRD trial), patients randomized to low protein diets experienced the same rate of decline of renal disease as normal protein.  Studies have clearly shown that clinical efforts such as tight blood pressure control or reduction of proteinuria are far more effective in slowing the progression of renal disease of any type, but also of lupus nephritis. It is important to emphasize the need for your doctor to regularly measure the amount of protein in your urine and to monitor various clinical markers of disease activity (Please see Question #5).

12. Can you explain the importance of testing for protein in the urine and at what level would the doctor feel the need to do further testing and treatment?  Where would you like to see a patient’s protein level?

The measurement and tracking of protein losses in the urine is one of the more important aspects of disease management in SLE. Protein in the urine can be benign but it is never normal. It remains the best and most consistent marker of disease activity in the kidney.  As for where a person’s protein should be---the best result would be no protein in the urine. Patient’s can have up to 150 mg of protein per 24 hours and still be considered “normal”.  Patients with protein between 15-300 mg are considered to have micro albuminuria while patients with greater than 300 mg are considered to have overt proteinuria. Patients with significant levels of proteinuria are considered to have “nephrotic range” proteinuria and should undergo renal biopsy to help define the stage of lupus nephritis and degree of renal damage. I would also emphasize and encourage patients to “partner” with their doctor to track the amount of proteinuria in your urine. This will help you to be a more informed patient and to assist your physician in your overall care.

13. Could kidney stones be a symptom of lupus?  Poteet, TX

Good question. Yes patients with involvement of the “tubule” portion of the kidney result in changes in the urine that predispose a person to the development of kidney stones. When tubules are scarred or damaged from Lupus nephritis, their ability to acidify the urine can be impaired. This can increase the incidence of various types of kidney stones. Moreover, damaged tubules also may be impaired in the production of citrate which is necessary for binding to calcium and preventing the calcium from forming into a stone. The usual maneuvers to prevent stones in a Lupus patient are the same as those for the general population. These include drinking a minimum of 2 liters of fluid per day and if the individual is shown to be citrate deficient to supplement these levels.    

14. What are the most effective treatments for lupus nephritis?  I recently had a Kidney biopsy showing the Lupus was affecting my Kidneys with a Class 5 Lupus Nephritis. I am treating with Cytoxan every 4 weeks and 60 mg of prednisone daily.  I want to be as aggressive in treatment as I can, so I clearly want to beat this.  Is there more aggressive treatment with a better success rate than 60%?  St. Louis, MO

That is a really comprehensive question. Let me start by noting that Class V lupus nephritis is sub-divided into to four subgroups that vary in their risk for progression to ESRD. For example, the World Health Organization (WHO) Class Va and Vb are comparatively mild and exhibit a much reduced risk for progression to dialysis. In contrast, WHO Class Vc and Vd are two of the most aggressive forms of Lupus nephritis. Your current therapy is fairly aggressive and mirrors the “classic NIH” induction protocol. This same protocol has been directly compared with oral CellCept (mycophenolate mofetil) and shown to have equivalence. Having said that there have been no trials in which these two treatments options have been compared in patients that have a feature on their biopsy called a crescent. It is important for the readers to understand that crescents in Lupus nephritis are important markers of severe disease. Studies have also shown that if a patient is treated for Lupus nephritis and the crescents persist after treatment, those individuals have a high (75%) chance of progressing to ESRD over 5 years. So how does this apply to your particular situation depends on your kidney biopsy. If you have WHO Class Vc or Vd and in addition have the presence of crescents, I would agree with your physician in the use IV Cytoxan. Other options are also available and can be reviewed on the Lupus Foundation of America website.

15. I have SLE and Polycystic kidney disease (PKD). Can you tell me if there is any impact on either disease to the other?  Cape Elizabeth, ME

Answer: Yes a combined lesion of SLE and PCKD disease is important in that you have two completely different disorders that are affecting kidney function. Moreover, the treatment for the two diseases is very different. You did not mention whether your Lupus involved your kidney.  If it does, I am unaware of PCKD being a contraindication to typical therapeutic options in SLE with the exception of Cyclosporin A or FK-506. These two agents are often used to treat the proteinuria in Lupus but unfortunately have the side effect of inducing fibrosis in the kidney. Thus, use of either of these drugs in a person with PCKD could in theory do additional damage to the tubules of the kidney that have already been compromised by the PCKD disease.