Urinary Albumin Fragments as a New Clinical Parameter for the Early Detection of Diabetic Nephropathy.

Yagame, Mitsunori; Suzuki, Daisuke; Jinde, Kiichiro; Yano, Naohiro; Naka, Raita; Abe, Yoshifumi; Nomoto, Yasuo; Sakai, Hideto; Suzuki, Hirokazu; Ohashi, Yoshitami

doi:10.2169/internalmedicine.34.463

Cited by 26 publications

(15 citation statements)

References 10 publications

(11 reference statements)

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“…It is probable that immunochemically nonreactive albumin is formed as a result of renal passage, although we cannot eliminate the possibility that it is present in low concentrations in blood and that its removal is facilitated by renal clearance. It is of interest that a similar molecule was proposed by Yagame et al (11 ), although they demonstrated the presence of albumin fragments by reducing SDS-PAGE and did not demonstrate that the molecule ever existed in an intact form. They did demonstrate the prevalence of relatively large albumin fragments in diabetic urines compared with control urines.…”

Section: Discussionmentioning

confidence: 79%

Characterization of Immunochemically Nonreactive Urinary Albumin

Osicka

Comper

2004

Clinical Chemistry

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Background: Conventional immunoassays underestimate the urinary albumin concentration because intact albumin in urine exists in two forms, immunoreactive and immunochemically nonreactive. Methods: Urinary albumin concentration measured by HPLC (which measures total albumin, i.e., the sum of immunoreactive albumin ؉ immunochemically nonreactive albumin) or RIA was compared with densitometric analysis of albumin bands in diabetic urine samples separated by either native polyacrylamide gel electrophoresis (PAGE) or reducing sodium dodecyl sulfate (SDS)-PAGE. Immunochemically nonreactive albumin was also isolated from diabetic urine (relative amount detected, 70 -80% of the expected) and was tested for contamination by common urinary proteins by native PAGE, ELISA, and capillary electrophoresis. Results: Urinary albumin concentrations measured by native PAGE and HPLC were better correlated (r 2 ‫؍‬ 0.83) than concentrations measured by native PAGE and RIA (r 2 ‫؍‬ 0.62) because under native conditions both native PAGE and HPLC detect total albumin and not only the immunoreactive albumin alone that is measured by RIA. Urinary albumin concentrations measured by reducing SDS-PAGE and RIA were better correlated (r 2 ‫؍‬ 0.84) than concentrations measured by reducing SDS-PAGE and HPLC (r 2 ‫؍‬ 0.65) because under reducing conditions immunochemically nonreactive albumin is unstable and fragments into many smaller peptides. The partially purified preparation was found to contain <1% contamination by common urinary proteins and is stable to freezing and frequent freeze/thaw cycles. Conclusions:The results are consistent with the interpretation that immunochemically nonreactive albumin

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Section: Discussionmentioning

confidence: 79%

Characterization of Immunochemically Nonreactive Urinary Albumin

Osicka

Comper

2004

Clinical Chemistry

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“…11 Other reports have, by mass spectrometry analysis, further identified albumin fragments in normal plasma 23,24 as well as plasma of patients with focal segmental glomerulosclerosis, 25 uremia, 26 and diabetes. 10 This finding stands in contrast to studies based on tritium-labeled albumin, where the majority of these studies found no LMW albumin in plasma, 19,27 although small amounts of tritiumlabeled fragments in plasma have been reported. 9 In this study, we have used albumin with a higher specific activity than the mentioned studies, which likely explains why we were able to detect the low amounts of labeled LMW albumin found in plasma.…”

mentioning

confidence: 79%

“…[7][8][9]29 A study in diabetic patients found no correlation between the urinary excretion of albumin fragments and b 2 -microglobulin, also supporting the concept that changes in the excretion of urinary albumin fragments is not associated with proximal tubule dysfunction. 10 Based on the finding of albumin fragments in plasma, it is, therefore, more likely that changes in urinary excretion of albumin fragments reflect alterations in extrarenal albumin metabolism and/or glomerular filtration.…”

mentioning

confidence: 99%

Generation of Urinary Albumin Fragments Does Not Require Proximal Tubular Uptake

Weyer

Nielsen²,

Christensen³

et al. 2012

Journal of the American Society of Nephrology

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Urinary albumin excretion is an important diagnostic and prognostic marker of renal function. Both animal and human urine contain large amounts of albumin fragments, but whether these fragments originate from renal tubular degradation of filtered albumin is unknown. Here, we used mice with kidneys lacking megalin and cubilin, the coreceptors that mediate proximal tubular endocytosis of albumin, to determine whether proximal tubular degradation of albumin forms the detectable urinary albumin fragments. After intravenous administration of 125 I-labeled mouse albumin to knockout and control mice, we examined kidney uptake of albumin and urinary excretion of both intact albumin and its fragments using size exclusion chromatography. In control mice, all labeled albumin eluted as albumin fragments in the urine. In megalin/cubilin-deficient mice, we observed decreased uptake and degradation of albumin and increased urinary excretion of intact albumin; we did not, however, detect a decrease in the excretion of albumin fragments. These results show that the generation of urinary albumin fragments occurs independently of renal tubular uptake and degradation of albumin, suggesting that the pathophysiological implications of changes in urinary albumin fragments require reevaluation.

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“…Albumin molecules are thought to be fragmented during renal passage in healthy samples [20][21][22][23][24]. The TIA method is commonly used for a urinary albumin diagnosis in Japan.…”

Section: Discussionmentioning

confidence: 99%

Presence of immunounreactive albumin in the urine of diabetic patients

Nakayama

Ida

Hatano

et al. 2006

Clinical Laboratory Analysis

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Recent studies have demonstrated that conventional immunochemical assays underestimate urinary albumin concentration because of the presence of immunounreactive albumin. It has been reported that intact urinary albumin in 24-hr diabetic urine samples could be detected as total concentration (immunoreactive+immunounreactive) by an HPLC method based on size exclusion chromatography. The aim of this study was to investigate urinary albumin concentration in diabetic spot urine samples by comparing the HPLC method with several other methods. The albumin concentrations on 80 diabetic spot urine specimens were measured by turbidimetric immunoassay (TIA), high performance liquid chromatography (HPLC), and a dipstick method. In addition, they were also analyzed by reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) and native polyacrylamide gel electrophoresis (Native PAGE). The albumin concentrations derived from diabetic spot urine samples measured by the HPLC method were higher than those of the other methods except for five of 80 samples. Furthermore, the albumin concentrations analyzed by Native PAGE were higher than SDS PAGE in 61 (76.2%) of 80 samples. This study suggests the need for evaluating diabetes not only by HPLC, but also by combining it with another method.

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Urinary Albumin Fragments as a New Clinical Parameter for the Early Detection of Diabetic Nephropathy.

Cited by 26 publications

References 10 publications

Characterization of Immunochemically Nonreactive Urinary Albumin

Characterization of Immunochemically Nonreactive Urinary Albumin

Generation of Urinary Albumin Fragments Does Not Require Proximal Tubular Uptake

Presence of immunounreactive albumin in the urine of diabetic patients

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