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Researchers Recommend Newer Methods To Assess Kidney Disease In Newly Diagnosed Multiple Myeloma Patients

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Published: Aug 28, 2013 3:20 pm

Findings from a recent study indicate that a newer method of determining kidney disease in multiple myeloma patients may be more accurate than traditional methods.

Researchers from Greece found that when they used the newer method, which tests for a protein known as cystatin-C, they were able to detect kidney damage in a higher percentage of newly diagnosed multiple mye­loma patients.

The investigators recommend that newer methods that include cystatin-C should be used instead of older methods, which rely only on measures of a compound called creatinine.

However, they note that larger prospective studies are needed to determine whether a method based on both creatinine and cystatin-C levels is more accurate than a method based on cystatin-C levels alone.

The researchers also caution that cystatin-C can be affected by other conditions, such as thyroid dysfunction, or the use of glucocorticoids, such as dexamethasone (Decadron) and prednisone. Therefore, they also state that further studies are needed to determine whether methods using cystatin-C can be reliably used to detect kidney damage in patients who have been treated with anti-myeloma therapies.

Background

Kidney impairment is a common myeloma-related complication that occurs in nearly 20 percent of newly diagnosed patients. It is primarily caused by the accumulation of antibody proteins called free light chains in the kidneys.

The most accurate method of assessing kidney damage currently is to directly measure a patient’s glomerular filtration rate (GFR), the rate at which the kidneys filter fluid. However, the Greek researchers point out that directly measuring GFR is time-consuming, expensive, and not always readily available in many hospitals.

GFR can be estimated based on a patient’s creatinine level in the blood or urine.  Creatinine is a protein found in the body’s muscles. It is routinely removed from the blood by the kidneys, but when the kidneys are not functioning properly, creatinine cannot be easily removed.

The researchers note, however, that creatinine may not be the most accurate method of assessing kidney damage, particularly in patients with early-stage kidney damage and those with reduced muscle mass.

Findings from one of their previous studies show that patients with kidney damage tend to have higher levels of cystatin-C than those with no kidney problems.  Cystatin-C is a protein that is found in almost all tissues and blood, and it is removed from the body via the kidneys.

Another retrospective study also showed that a newer method that combines serum creatinine and cystatin-C levels more accurately estimates GFR than creatinine or cystatin-C alone.

Thus in the current study, the researchers sought to prospectively evaluate newer methods of determining kidney damage based on levels of both creatinine and cystatin-C.

Study Design

Investigators from four major hospitals in Athens and Thessaloniki, Greece, assessed kidney damage in 220 newly diagnosed multiple myeloma patients and 52 healthy individuals. The median age was 69 years for the myeloma patients, and 68 years for the healthy individuals.

None of the myeloma patients had previously received treatment.

The investigators compared four different methods of determining kidney impairment.

The first method, called Modification of Diet in Renal Disease (MDRD), is based on creatinine levels in the blood, age, ethnicity, and gender.

The second method, abbreviated as CKD-EPI, is based on creatinine levels alone.

The third method, abbreviated as CKD-EPI-CysC, is based on cystatin-C levels alone.

The fourth method, abbreviated as CKD-EPI-sCr-CysC, is based on both creatinine and cystatin-C levels

Results

The investigators found that median cystatin-C levels were increased in myeloma patients compared to the healthy individuals (1.07 mg/L versus 0.72 mg/L, respectively).

According to the researchers, the normal range for cystatin-C levels is between 0.53 mg/L and 0.95 mg/L.

Overall, 61 percent of the myeloma patients had elevated cystatin-C levels. In comparison, only 26 percent of the myeloma patients had elevated creatinine levels.

In addition, the researchers found that elevated cystatin-C levels were associated with advanced disease. Patients with stage 3 myeloma according to the International Scoring System (ISS) had higher median cystatin-C levels (1.91 mg/L) than stage 2 (0.96 mg/mL) and stage 1 patients (0.83 mg/L).

When comparing the four methods of determining kidney damage, the investigators found that the two methods including cystatin-C levels, CKD-EPI-sCr-CysC and CKD-EPI- CysC, identified more patients with moderate to severe chronic kidney disease.

Overall, 45 percent of patients were classified as having moderate to severe chronic kidney disease according to the CKD-EPI-sCr-CysC method, compared to 43 percent according to the CKD-EPI-CysC method, 42 percent by the CKD-EPI method, and 40 percent by the MDRD method.

Furthermore, 29 percent of the patients were reclassified to higher chronic kidney disease stages when the CKD-EPI-CysC method was used, compared to the MDRD method.

When the researchers grouped the patients by age, they found that the CKD-EPI-sCr-CysC method was the most accurate in identifying patients above 70 years of age with moderate to severe chronic kidney disease. For patients ages 70 years and below, the CKD-EPI-CysC method produced the most accurate results.

Based on these findings, the researchers recommend that more research be carried out to determine which of the two cystatin-C methods is the most accurate in measuring kidney function in myeloma patients.

The median overall survival for all myeloma patients in the study was 52 months.

To see which method of calculating kidney function was best at predicting patient survival, the researchers analyzed to what degree disease stage, kidney function, and lactate dehydrogenase (LDH) levels together affect survival.  This analysis was done four times — once for each of the four measures of kidney function.

These analyses found that LDH level was the only factor consistently predictive of patient survival.  The only measure of kidney function that was significantly predictive of survival was the CKD-EPI-CysC method.

For more information, please refer to the study in the European Journal of Haematology (abstract).

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6 Comments »

  • Eric said:

    Without actually being presented with the accuracy of the prediction calculations, do you think that one method is superior to the others when all predict kidney damage in 40-45 percent of the patients studied? This study does not seem to warrant changes in prediction method for kidney impairment from the standard method.

  • Boris Simkovich said:

    Thanks for your question, Eric.

    You’re right that, on the surface, it looks like the four measures don’t differ that much from one another in practical terms.

    The issue is that, when you look below the surface, you find that the similarity ends.

    When it comes to estimating the degree of a patient’s kidney damage, for example, the agreement between the newer CKD-EPI-CysC method and the older MDRD method was only 60 percent.

    So, although on average it looks like the methods are coming up with similar results, they actually differ when you start looking at individual patients.

    Now, you could ask: “Okay, there’s disagreement between the methods at the individual patient level, but why should we assume that the newer methods are actually better?”

    Well, first of all, there’s previous research that shows that the CysC methods are, in fact, better at estimating kidney damage, as reflected in the actual glomerular filtration rate (GFR).

    But the most compelling argument, which was alluded to in our article, is that the CysC-based methods are better at predicting overall survival.

    For example, you can use each of the methods to split the myeloma patients into two groups — those with moderate to severe kidney damage, and those without.

    If you do that, you find that there is a bigger difference in survival between these two patient groups when you use the CysC-based methods than the older, creatinine-based methods.

    In other words, the CysC-based methods give physicians a more accurate picture of just how serious a patient’s myeloma is.

    If you wish, we can put up some survival curves from the article to illustrate the point I just made.

    Thanks again for your question.

  • Eric said:

    Boris

    Thanks for the reply and further explanation. I would like to see the survival curves you mentioned, since this may better illustrate the benefit of the new method of kidney damage measurement / prediction. I look forward to being able to see the graphical data. Thanks very much.

  • Boris Simkovich said:

    Sure, Eric. I’ll get the graphs up later today (Friday), or sometime early tomorrow. They’ll be here in the comments.

  • Boris Simkovich said:

    Here you go, Eric.

    First, here are the overall survival curves for patients in the study using the MDRD method to categorize patients based on their kidney damage. Patients with CKD (“chronic kidney disease”) stage 1 and 2 have no, or mildly reduced, kidney function. Patients with CKD stages 3 to 5 have moderate to very severe kidney damage.

    MMOS-MDRD

    And these are the overall survival curves for the same patients, but using the CKD-EPI-CysC method to categorize patients based on kidney damage.

    MMOS-CKD-EPI-CysC

    I won’t show them here, but the graph using the CKD-EPI method looks very similar to the MDRD graph above, and the graph using the CKD-EPI-sCr-CysC method looks very similar to the CKD-EPI-CysC graph above.

  • Eric said:

    Boris

    Thanks for the additional graphs. It is obvious from the CKD-EPI-CysC graph that stage 3 to 5 CKD have dramatically poorer survival prediction than the MDRD method. Thanks for extra information.