Urine β2-microglobulin is associated with clinical disease activity and renal involvement in female patients with systemic lupus erythematosus

Choe, Jeong‐Sook; Park, Sang Hoon; Sk, Kim

doi:10.1177/0961203314547797

Cited by 24 publications

(23 citation statements)

References 23 publications

(51 reference statements)

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“…to define active disease. [28][29][30][31][32][33] Additionally, it is important to point out that the cut-off selection presented by Yee et al 24 underlines the importance of considering the SLEDAI-2K score as a continuous scale, especially in longitudinal studies. Therefore, in this study we also analyzed the relationship of dsDNA positivity by the CIA in relation to the SLEDAI-2K score and found significantly higher scores in the CIA-positive versus the CIA-negative SLE patients (p < 0.0001).…”

Section: Discussionmentioning

confidence: 99%

International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies

Bentow

Lakos

Martis

et al. 2016

Lupus

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Section: Discussionmentioning

confidence: 99%

International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies

Bentow

Lakos

Martis

et al. 2016

Lupus

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“…Collectively, the recent animal toxicology data raise important questions about both the specificity of urinary β 2 M for tubular lesions, i.e., this compound appears to detect glomerular injury better than tubular damage, and its overall utility relative to the more easily obtained assay for albuminuria. Interestingly, significant correlations between urinary β 2 M and other indices of renal damage (e.g., protein/Cr ratio) have been reported in IgA nephropathy (163) and systemic lupus erythematosus (164). Both these conditions are characterized by predominantly glomerular lesions.…”

Section: Urinary β2m For the Assessment Of Tubular Functionmentioning

confidence: 99%

“…After therapy, the serum β 2 M level decreased significantly (268). Urinary β 2 M has been shown to correlate with overall and renal disease activity scores and proteinuria (164). Patients with active primary Sjögren’s syndrome, notably those with increased systemic disease activity (302) and history of lymphoma (303, 304), and hemophagocytic lymphohistiocytosis (305) were also found to have elevated urinary β 2 M level.…”

Section: β2m In Non-renal Diseasesmentioning

confidence: 99%

“…Such studies are urgently needed, because the urinary β 2 M appears to have a much larger utility than previously recognized. Animal toxicology experiments conducted under rigorously controlled conditions (160, 162) and provocative observations in glomerular diseases (163, 164) suggest that urinary β 2 M may in fact be a better marker of glomerular than tubular damage. This finding, backed by controlled experiments in hundreds of animals and observations in a much smaller number of humans, seems to go against textbook dogma.…”

Section: β2m: Synthesis and The Way Forwardmentioning

confidence: 99%

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Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

et al. 2017

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There is currently an unmet need for better biomarkers across the spectrum of renal diseases. In this paper, we revisit the role of beta-2 microglobulin (β2M) as a biomarker in patients with chronic kidney disease and end-stage renal disease. Prior to reviewing the numerous clinical studies in the area, we describe the basic biology of β2M, focusing in particular on its role in maintaining the serum albumin levels and reclaiming the albumin in tubular fluid through the actions of the neonatal Fc receptor. Disorders of abnormal β2M function arise as a result of altered binding of β2M to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of β2M as a predictor of renal function and clinical outcomes in recent large database studies against predictions made by recently developed whole body population kinetic models. Furthermore, we discuss recent animal data suggesting that contrary to textbook dogma urinary β2M may be a marker for glomerular rather than tubular pathology. We review the existing literature about β2M as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that β2M is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of β2M as a biomarker in a number of non-renal diseases. The goal of this comprehensive review is to direct attention to the multifaceted role of β2M as a biomarker, and its exciting biology in order to propose the next steps required to bring this recently rediscovered biomarker into the twenty-first century.

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“…Proteins of low molecular weight, such as α1-microglobulin (α1-MG) (31.8 kD) or β2-microglobulin (β2-MG) (11.8 kD), are excreted in large quantities when proximal tubular cells lose their capacity to reabsorb them; therefore, these proteins reflect intrinsic tubular injury [ 19 ]. Studies have shown that serum and urinary levels of β2-MG were associated with renal involvement in SLE [ 20 , 21 ], as well as urinary albumin (UAL) [ 22 ], IgG, and α1-MG [ 23 ]. Physiologically, α1-MG is involved in the defense against oxidative tissue damage [ 24 ], while β2-MG is a component of the MHC class I [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Urinary Albumin Levels are Independently Associated with Renal Lesion Severity in Patients with Lupus Nephritis and Little or No Proteinuria

Ding

Zheng

et al. 2017

Med Sci Monit

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BackgroundSystemic lupus erythematosus (SLE) leads to renal lesions, which may be clinically silent in patients with little or no proteinuria. Early detection of these lesions may improve prognosis, but early markers are controversial. This study aimed to determine renal marker proteins associated with renal lesion severity in patients with lupus nephropathy (LN) and little or no proteinuria.Material/MethodsPatients with LN and little or no proteinuria (<0.5 g/24 hours) (n=187) that underwent kidney biopsy were grouped according to: low severity (Class I or II; n=116) versus high severity (Class III, IV, or V; n=71). Disease status was determined according to the SLE disease activity index (SLEDAI). Renal marker proteins (serum β2-macroglobulin, urinary β2-macroglobulin, albumin, IgG, and α1-macroglobulin) were measured using radioimmunoassay.ResultsCompared with the low severity group, patients in the high severity group had higher urinary albumin (11.60±8.94 versus 7.08±10.07 μg/mL, p=0.008) and urinary IgG (13.21±9.35 versus 8.74±8.90 μg/mL, p=0.007) levels. Multivariate conditional logistic regression analysis showed that urinary albumin (odds ratio (OR)=1.417, 95% confidence interval (95% CI): 1.145–1.895, p=0.001) and SLEDAI (OR=2.004, 95% CI: 1.264–3.178, p=0.003) were independently associated with severe renal lesions in these patients. Using an optimal cutoff point of urinary albumin of 7.53 μg/mL resulted in 67% sensitivity and 82% specificity for the detection of high severity renal lesions.ConclusionsUrinary albumin levels and SLEDAI were independently associated with histological severity of renal lesions in patients with LN and little or no proteinuria. These parameters could be used to help select patients for renal biopsy.

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Urine β2-microglobulin is associated with clinical disease activity and renal involvement in female patients with systemic lupus erythematosus

Abstract: We demonstrated that urine β2MG levels are associated with renal involvement and overall clinical disease activity in SLE.

Cited by 24 publications

References 23 publications

International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies

International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies

Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

Urinary Albumin Levels are Independently Associated with Renal Lesion Severity in Patients with Lupus Nephritis and Little or No Proteinuria

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