Proteinuria selectivity index based upon α2-macroglobulin or IgM is superior to the IgG based index in differentiating glomerular diseases

Tencer, Jan; Torffvit, Ole; Thysell, Hans; Rippe, Bengt; Grubb, Anders

doi:10.1046/j.1523-1755.1998.00205.x

Cited by 48 publications

(30 citation statements)

References 29 publications

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“…The assays were performed essentially as described for the IgM assay [22]. Human IgG2, IgG4, and IgM were purchased from The Binding Site (Birmingham, UK).…”

Section: Methodsmentioning

confidence: 99%

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Size and Charge Selectivity of the Glomerular Filter in Patients with Insulin-Dependent Diabetes mellitus: Urinary Immunoglobulins and Glycosaminoglycans

Torffvit¹,

Rippe

1999

Nephron

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Background: In diabetic nephropathy, a reduction in negative membrane charge in the glomerular filter, i.e., the number of sulphated groups of glycosaminoglycans, has been argued to lead to increases in excretion of negatively charged molecules, such as albumin and IgG4. However, albuminuria and an increased excretion rate of IgG may also be caused by an increase in radius or number of glomerular large pores. Methods: Timed urinary excretion rates of sulphated glycosaminoglycans, albumin, and IgG2, IgG4, and IgM were analyzed in 94 patients with insulin-dependent diabetes mellitus with different degrees of nephropathy and compared with the excretion rates in 26 control subjects. Sulphated glycosaminoglycans were measured spectrophotometrically after addition of 1,9-dimethylmethylene blue. Albumin and immunoglobulins were measured by immunoassays. Results: With increases in the albumin excretion rate the excretion of IgG2, IgG4, and IgM also increased, in contrast to a decrease in glycosaminoglycans and the ratio between IgG2 and IgG4 (selectivity index). This index decreased from 6.2 to 0.7 (median; p < 0.01). However, with linear regression analysis the excretion rates of albumin and immunoglobulins were not associated with those of glycosaminoglycans. Conclusion: In diabetic nephropathy changes in both large-pore number and in charge selectivity may be pathogenic mechanisms for albuminuria.

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“…The assays were performed essentially as described for the IgM assay [22]. Human IgG2, IgG4, and IgM were purchased from The Binding Site (Birmingham, UK).…”

Section: Methodsmentioning

confidence: 99%

“…The standard curve obtained at each plate was used to calculate the concentrations in the urine samples. Buffer solutions for coating, incubation, and substrate have previously been described for the IgM assay [22]. …”

Section: Methodsmentioning

confidence: 99%

Size and Charge Selectivity of the Glomerular Filter in Patients with Insulin-Dependent Diabetes mellitus: Urinary Immunoglobulins and Glycosaminoglycans

Torffvit¹,

Rippe

1999

Nephron

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“…Tencer et al reported the proteinuria selectivity index as useful to describe changes of the glomerular permeability for macromolecules in glomerular diseases [13]. Proteins the size of A2M cannot normally pass the glomerular barrier.…”

Section: Discussionmentioning

confidence: 99%

Urinary Biomarkers for Kidney Disease in ATTR Amyloidosis

F¹

2014

J Nephrol Ther

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“…The rationale for using nonalbumin proteinuria as a surrogate for nonselective proteinuria is as follows: In patients with overt glomerulopathy, (1) increasing proteinuria is associated with increasing albuminuria ( Figure 1). (2) As albuminuria increases, also increased is the excretion of both high molecular weight proteins (e.g., IgG, ␣ 2 macroglobulin, and IgM) and low molecular weight proteins (e.g., ␤ 2 microglobulin) (33)(34)(35). Thus, nonalbumin proteinuria (P-C ratio Ϫ A-C ratio) increases.…”

Section: Figure 2 Relationship Between P-c Ratio and The Proportion mentioning

confidence: 99%

Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis

Birmingham¹,

Rovin²,

Shidham³

et al. 2008

Clinical Journal of the American Society of Nephrology

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Background and objectives: Albuminuria is regarded a sensitive measure of progression of glomerular disease. This study was undertaken in patients who had systemic lupus erythematosus glomerulonephritis (n ‫؍‬ 57) and were followed in the Ohio SLE Study to determine whether measuring albuminuria offered clinical advantages over that of total proteinuria. Design, setting, participants, & measurements: Twenty-four-hour urine collections (n ‫؍‬ 127) were obtained at baseline and annually for measurement of microalbumin, total protein, and creatinine.Results: There was a strong linear relationship between microalbumin-creatinine and protein-creatinine ratios over the entire range of protein-creatinine ratios; however, in the protein-creatinine ratio range 0.0 to 0.3, as the protein-creatinine ratio increased, the microalbumin-protein ratio increased much more than the protein-creatinine ratio. Also, the greater the protein-creatinine ratio, the greater was the evidence for nonselective proteinuria (protein-creatinine ratio ؊ microalbumincreatinine ratio).Conclusions: For the diagnosis of proteinuria renal flare, measuring albuminuria offers no advantage over measuring total proteinuria because changes in protein-creatinine and microalbumin-creatinine ratios are highly correlated over the designated ranges for systemic lupus erythematosus glomerulonephritis proteinuric flares. In those with normal-range proteinuria, subsequent changes in microalbumin-protein ratio might be a better forecaster of renal flare than changes in proteincreatinine or microalbumin-creatinine ratio. High protein-creatinine ratios are associated with evidence of nonselective proteinuria, which may increase the nephrotoxicity of proteinuria. Thus, using high-threshold criteria for systemic lupus erythematosus flare (allowing greater proteinuria increase before flare is declared) may expose the kidney to greater nephrotoxicity than using the low-threshold criteria for systemic lupus erythematosus flare.

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Proteinuria selectivity index based upon α2-macroglobulin or IgM is superior to the IgG based index in differentiating glomerular diseases

Abstract: The findings of this study indicate that alpha 2M SI and IgM SI are superior to IgG SI in characterization of glomerular disorders and might replace the IgG SI for this purpose.

Cited by 48 publications

References 29 publications

Size and Charge Selectivity of the Glomerular Filter in Patients with Insulin-Dependent Diabetes mellitus: Urinary Immunoglobulins and Glycosaminoglycans

Size and Charge Selectivity of the Glomerular Filter in Patients with Insulin-Dependent Diabetes mellitus: Urinary Immunoglobulins and Glycosaminoglycans

Urinary Biomarkers for Kidney Disease in ATTR Amyloidosis

Relationship between Albuminuria and Total Proteinuria in Systemic Lupus Erythematosus Nephritis

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