Association between the Delta Estimated Glomerular Filtration Rate and the Prevalence of Monoclonal Gammopathy of Undetermined Significance in Korean Males

Background. We investigated the association between the reduction in the estimated glomerular filtration rate (eGFR) and the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in Korean males. Methods. We enrolled 723 healthy Korean males. Serum creatinine concentration, serum electrophoresis, serum immunofixation, and the serum free light chain assay were performed. We calculated delta eGFR per year (ΔeGFR/yr). The prevalence of MGUS was compared based on the ΔeGFR/yr and age group. Results. Thirteen (1.8%) of 723 participants exhibited the monoclonal band on serum immunofixation. Prevalence of MGUS by age group was 0.00% (0/172 for 40 years), 1.63% (6/367 for 60 years), and 3.80% (7/184 for >60 years). The median decrease in ΔeGFR/yr was 5.3%. The prevalence of MGUS in participants in their 50s with >5.3% decline in ΔeGFR/yr was significantly higher than those with <5.3% decrease in ΔeGFR/yr (3.16% versus 0.00%; P = 0.049). The prevalence of MGUS in participants in their 50s with >5.3% decrease in ΔeGFR/yr was similar to that of healthy males in their 60s. Conclusion. Using the rate of reduction in ΔeGFR/yr in healthy Korean males who had their serum creatinine level checked regularly may increase the MGUS detection rate in clinical practice.

Several studies of the prevalence of MGUS stratified by age category in each race have been conducted. However, to the best of our knowledge, none has reported the correlation between the degree of estimated glomerular filtration rate (eGFR) reduction and the prevalence of MGUS. And the association between measurement of free kappa and lambda light chains by the serum FLC assay and the prevalence of MGUS has not been well documented either. Thus, in this study we investigated the correlation between the degree of egfr reduction and MGUS prevalence among Korean healthy males.
The MGUS prevalence in participants with kappa or lambda FLC concentrations higher than the reference value on sFLC was 10.91% (6/55), significantly higher than the 1.05% (7/668) in those with a normal serum kappa and lambda FLC concentration.

Discussion
We investigated the association between ΔeGFR/yr and prevalence of MGUS in healthy Korean males aged over 40 years. Our results showed that MGUS prevalence values in Korean men in their 40 (0.00%), 50 (1.63%), and >60 years of age (3.80%) were similar to MGUS values for Japanese males in their 40 (1.2%), 50 (2.7%), and >60 years of age (4.3%) and Chinese men 50-65 years (1.2%) [8,9]. To date, the MGUS prevalence in Koreans has been determined only in elderly people >65 years [3]. In the present study, the prevalence of MGUS in participants >60 years was 3.80% which was similar to those obtained from elderly Korean male aged over 65 years (3.8%) [3].
By definition of MGUS, there is no renal insufficiency. However, excess serum free light chains and intact immunoglobulins that exceed the metabolic ability of kidney function in patients with MGUS can accumulate in the kidney, resulting in subclinical renal insufficiency such as a decline in GFR [10,11]. On the basis of above consideration, we had assumed that the prevalence of MGUS may be higher in patients with markedly reduction of GFR. And the GFR decline may occur within reference range of serum creatinine. In our study, although the prevalence of MGUS in all participants was not significantly different based on the ΔeGFR, a statistically significant difference was found in the group in their 50s. The difference between the 50s group and those >60 can be partially explained that MGUS is not always a premalignant lesion. Our study indicated that there was apparent association between the MGUS and ΔeGFR; however, a large-scale cohort study is needed to reach the statistical significance.
According to the current MGUS management guideline, MGUS does not require aggressive treatment [12]. However, MGUS is an obvious premalignant lesion that requires careful observation because it progresses to multiple myeloma or other plasma cell-related disorders in some patients [12][13][14][15]. In this study, the MGUS prevalence in the group with ≥5.3% decline in ΔeGFR/yr was almost threefold that in the other groups. The prevalence of MGUS in participants in their 50s with a high rate of decrease in ΔeGFR/yr was 3.16%, which was similar to that in the group in their 60s. As 10-20% of those with MGUS in this group are likely to develop multiple myeloma or diverse malignant plasma cell disorders when they reach 60-70 years of age, early detection of MGUS in 50s should be considered.
Measurement of serum creatinine level is included in the National Health Screening Program organized by the National Health Insurance Service for Koreans who are required to undergo a regular health checkup every year or 2 years. And the ΔeGFR can be calculated from those data. We thought that addition of screening for monoclonal protein in those whose ΔeGFR/yr shows a marked reduction may increase the MGUS diagnostic rate.
In this study, we observed 9 samples of false-negative results for sFLC assay based on the sIFE findings. We thought that possible sources of false-negative results of sFLC assay were antigen excess [16], FLC polymerization [17], and polyclonal FLC elevation [18]. On the other hand, sFLC assay demonstrated false-positive results for 17 samples based on the sIFE findings. Seventeen participants were normal on the sIFE and sPEP tests but had an abnormal sFLC ratio. Among them, 15 participants showed kappa clonality which means that their sFLC ratio showed more than 1.65 and the remaining 2 participants demonstrated lambda clonality which means that their sFLC ratio is less than 0.26 (data not shown). It has been well documented that sFLC assay could detect monoclonal protein more sensitive than sPEP and sIFE assay [6,19]. So it is not clear whether 17 samples are true false-positive results. These 17 participants may have monoclonal protein in their sera. So we thought that they need to be monitored to identify monoclonal protein.
In conclusion, the prevalence of MGUS in healthy Korean males in their 50s with a decrease in ΔeGFR/yr of ≥5.3% was significantly higher than those with a decrease in ΔeGFR/yr of <5.3%. Additionally, the prevalence of MGUS was similar to that of healthy Korean males in their 60s. Using ΔeGFR/yr in healthy Korean males whose serum creatinine level is checked regularly may facilitate early detection of MGUS.