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      Serum β2-Microglobulin Correlates Positively with Left Ventricular Hypertrophy in Long-Term Hemodialysis Patients

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          Background/Aims: β<sub>2</sub>-Microglobulin (β<sub>2</sub>-MG) is a major protein component of dialysis-related amyloidosis. In long-term hemodialysis (HD) patients, β<sub>2</sub>-MG amyloid deposits not only in osteoarticular tissues, but also in systemic tissues, including the heart. The purpose of this study was to investigate the relationship between serum β<sub>2</sub>-MG concentrations and echocardiographic parameters in long-term HD patients in a cross-sectional study. Methods: Measurement of serum β<sub>2</sub>-MG concentrations and echocardiography were performed in 251 patients who had undergone HD therapy for more than 10 years. Results: The left ventricular mass index (LVMI) of the higher serum β<sub>2</sub>-MG (≥30 mg/l) group was significantly higher than that of the lower serum β<sub>2</sub>-MG (<30 mg/l) group (151.5 ± 45.7 vs. 137.0 ± 44.5 g/m<sup>2</sup>, p = 0.020). In simple regression analyses, serum β<sub>2</sub>-MG concentrations correlated significantly and positively with interventricular septum thickness (IVST) (r = 0.215, p < 0.001), posterior left ventricular wall thickness (PWT) (r = 0.249, p < 0.001), left ventricular wall thickness (LVWT) (r = 0.252, p < 0.001), relative wall thickness (RWT) (r = 0.153, p = 0.015) and LVMI (r = 0.171, p = 0.007). Multiple regression analyses revealed that serum β<sub>2</sub>-MG concentrations correlated significantly and positively with IVST, PWT, LVWT and RWT. Conclusion: Serum β<sub>2</sub>-MG concentrations correlated significantly and positively with the echocardiographic parameters of left ventricular hypertrophy (LVH) in long-term HD patients. Thus, deposition of β<sub>2</sub>-MG amyloid in the heart may be associated with LVH progression.

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          Most cited references 9

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          Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.

          To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society of Echocardiography (ASE) conventions and cube function and volume correction formulas in 52 patients. Penn-cube LV mass correlated closely with necropsy LV mass (r = 0.92, p less than 0.001) and overestimated it by only 6%; sensitivity in 18 patients with LV hypertrophy (necropsy LV mass more than 215 g) was 100% (18 of 18 patients) and specificity was 86% (29 of 34 patients). ASE-cube LV mass correlated similarly to necropsy LV mass (r = 0.90, p less than 0.001), but systematically overestimated it (by a mean of 25%); the overestimation could be corrected by the equation: LV mass = 0.80 (ASE-cube LV mass) + 0.6 g. Use of ASE measurements in the volume correction formula systematically underestimated necropsy LV mass (by a mean of 30%). In a subset of 9 patients, 3 of whom had technically inadequate M-mode echocardiograms, 2-dimensional echocardiographic (echo) LV mass by 2 methods was also significantly related to necropsy LV mass (r = 0.68, p less than 0.05 and r = 0.82, p less than 0.01). Among other indexes of LV anatomy, only measurement of myocardial cross-sectional area was acceptably accurate for quantitation of LV mass (r = 0.80, p less than 0.001) or diagnosis of LV hypertrophy (sensitivity = 72%, specificity = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)
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            Serum beta2-microglobulin level is a significant predictor of mortality in maintenance haemodialysis patients.

            Beta(2)-microglobulin (beta(2)-M) is recognized as a surrogate marker of middle-molecule uraemic toxins and is a key component in the genesis of dialysis-associated amyloidosis. Few studies have evaluated the association of beta(2)-M levels with clinical outcome in dialyzed patients. The prognostic implication of serum beta(2)-M levels for the survival of haemodialysis patients was examined in 490 prevalent haemodialysis patients (60.1 +/- 11.8 years, haemodialysis duration of 87.4 +/- 75.7 months, 288 males and 202 females; 24% diabetics). The patients were divided into two groups according to their serum beta(2)-M levels: lower beta(2)-M group (n = 245) with serum beta(2)-M or=32.2 mg/L. During the follow-up period of 40 +/- 15 months, there were 91 all-cause deaths, and out of them, 36 were from cardiovascular diseases. Kaplan-Meier analysis revealed that all-cause mortality in the higher beta(2)-M group was significantly higher compared to that in the lower beta(2)-M group (P < 0.001). Multivariate Cox proportional hazards analyses showed that serum beta(2)-M level was a significant predictor for all-cause mortality (hazard ratio, 1.05; 95% CI, 1.01-1.08; P = 0.005), and for non-cardiovascular mortality (hazard ratio, 1.06; 95% CI, 1.02-1.10; P = 0.006), after adjustment for age, gender, haemodialysis duration, the presence of diabetes, serum albumin and serum C-reactive protein. These results demonstrate that the serum beta(2)-M level is a significant predictor of mortality in haemodialysis patients, independent of haemodialysis duration, diabetes, malnutrition and chronic inflammation, suggesting the clinical importance of lowering serum beta(2)-M in these patients.
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              Among the uremic toxins in the "middle molecule" range, beta2-microglobulin (beta2-M) is certainly one of the most frequently studied compounds. Its serum level increases with the progression of chronic kidney disease, to reach very high concentrations in patients with end-stage kidney disease. It is the major protein component of dialysis-related amyloidosis, a dramatic complication which results from high extracellular concentration and posttranslational modification of beta2-M and a number of other promoters of amyloid fibril formation and deposition in osteo-articular tissues. Effective removal of beta2-M can be achieved with highly effective hemodialysis and hemodiafiltration techniques but predialysis session serum levels cannot be normalized. The prevalence and severity of beta2-M amyloidosis appear to have decreased in the last 20 years, although its occurrence may simply be delayed.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                December 2014
                04 November 2014
                : 128
                : 1-2
                : 101-106
                aDepartment of Metabolism, Endocrinology, Molecular Medicine, and Nephrology, Osaka City University Graduate School of Medicine, and bShirasagi Hospital, Osaka, and cInoue Hospital, Suita, Japan
                Author notes
                *Eiji Ishimura, MD, PhD, Department of Nephrology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan), E-Mail ish@med.osaka-cu.ac.jp
                365447 Nephron Clin Pract 2014;128:101-106
                © 2014 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 3, Pages: 6
                Original Paper


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