Diuresis-dependent excretion of multiple forms of renal brush-border enzymes in urine

Jung, Klaus; Schulze, G

doi:10.1016/0009-8981(86)90181-6

Cited by 16 publications

(16 citation statements)

References 10 publications

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“…I-ALP is restricted to the S3 segment of the proximal tubule, their simultaneous assay allowing renal injury to be localised to S3, S1/2 or the whole proximal convoluted tubule (30). The main problems in measuring enzymes in general are their lack of stability, interference from factors in the urine, and the fact that their release varies according to dieresis (31). Brush border enzymes may be found in the urine in two forms: soluble or bound to cell membrane fragments.…”

Section: N-acetyl-b-dglucosamidasementioning

confidence: 99%

Cell-Specific Biomarkers in Renal Medicine and Research

Shaw¹

2010

Methods in Molecular Biology

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Histopathology is the gold standard for defining renal injury, but it is invasive, time-consuming and expensive, plus it is seldom used in subjects with mild renal injury. Using biomarkers linked to distinct, defined cell types and tissues provides a direct link to histopathology without its drawbacks, plus it provides increased sensitivity, and specificity. The nephron consists of several sections, each with its own specific biomarkers; therefore, by the use of a battery of tests injuries can be localised to distinct areas of it. Using urine samples simplifies repeated sampling from the same subject or animal leading to better defined toxicokinetics and disease monitoring.Serum creatinine is the most widely used renal biomarker in spite of its known shortcomings. Cell-specific biomarkers are more specific and sensitive and have been known for over 40 years, but they are still underused in renal medicine and research. In particular, while many studies have shown cell-specific biomarkers to be valuable in diagnosis, there are few studies where they have been used to guide therapy or linked to quantitative changes in the kidney. Furthermore, the great majority of cell-specific biomarkers are from the proximal tubule, which may have hindered research into the study of conditions where the distal tubules are affected. Recently, the range of biomarkers and their applications has been expanded by the introduction of indicators of cellular regeneration.This chapter will discuss how using biomarkers with a known cellular origin, renal effects may be found earlier and at lower levels of injury. Their use in both renal medicine and drug research will be presented. Knowledge of these existing markers lays the foundation for evaluation, comparison, and characterisation of new markers that will be identified in the future.

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Section: N-acetyl-b-dglucosamidasementioning

confidence: 99%

Cell-Specific Biomarkers in Renal Medicine and Research

Shaw¹

2010

Methods in Molecular Biology

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“…For albumin, measured in urines of normal persons, Viberti et al (27,28) found ä large intra-individual Variation, which was pnjy slightly less when related to creatinine. Calculation of urinary enzyme activities, in relation to creatinine reduced the intra-individual variabilities (29,30,31). Our present results confirm and extend these pbservations.…”

Section: Biological Variation Of Urinary Proteinsmentioning

confidence: 99%

A Diagnostic Programme for Quantitative Analysis of Proteinuria

Hofmann

Guder²

1989

Clinical Chemistry and Laboratory Medicine

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Summary:A spectrum of quantitative methods was adapted to the Kone Specific Analyser for the purpose of recognizing, quantifying and differentiating various forms of proteinuria. Total protein, IgG, albumin and oci-microglobulin (measured by turbidimetry), N-acetyl-ß-.D-glucosaminidase activity and creatinine (measured photometrically), were measured in undiluted urine; in addition a r microglobulin was measured in serum.Within and between run predsion, accuracy and linearity of the turbidimetric methods were in good agreement with nephelometric procedures. All turbidimetric methods exhibited a correlation coefficient r > 0.98 when compared with the radial immunodiffusion procedure äs reference method. Total protein measured turbidimetrically with the Kone Specific Analyser was in good agreement with the manual biuret procedure.The low detection limits and linearities allowed quantification of urine analytes from the lower ränge of normals up to ten times the upper limit of normals.The measured analytes exhibited stability in urine at pH 4-8 over at least seven days at 4 -6 °C and -20 °C. Only IgG showed a significant loss (up to 30 percent), when measured after storage at -20 °C.Quantities per mol creatinine showed significantly lower intra-individual and inter-individual variability than quantities per liter. In 31 normal persons, the intraindividual Variation was lowest for N-acetyl-ß-Z>-glucosaminidase activity (13%) and highest for total protein (33%), when measured in the second morning urine on 5 consecutive days.When related to creatinine, resülts obtäined in the second morning urine showed no significant differences from those in 24 h urine, except for aj-microglobulin which gave lower values in 24 h urines.The upper normal limits, calculated äs the 95% ranges, were determined from 154 urines of 31 individuals. Nearly all analytes showed an asymmetric distribution. Because of a wide tailing of the upper limit, preliminary üpper normal limits were set aböve this ränge:Total protein: 7.9 g/mol creatinine (70 mg/g creatinine) IgG:1.13 g/mol creatinine (10 mg/g creatinine) Albumin:2.26 g/mol creatinine (20 mg/g creatinine) ocrMicroglobulin: " 1.58 g/mol creatinine (14 mg/g creatinine) N^Acetyl-ß-jD-glücosaminidäse: 0.56 kU/mol creatinine (5 U/g creatinine).Application of the newly adapted programme to unselected urines sent for urine analysis revealed a threefold incfease in the propörtion of resülts outside the normal ranges, compared with the routinely used protein test strip procedure. All additional positive urines exhibited either signs of glomerular or tubular proteinuria. Determination of albumin or N-acetyl-ß-jD-glucosaminidase excretion was sufficient to detect these additional cases.

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“…This may explain the fact that, to date, a valid biological marker of tubular maturation is lacking. Fractional tubular reabsorption of B2M, which has been proposed as a valid index of tubular matura tion and of the occurrence of glomerulo-tubu lar balance [11], has been shown to be in fluenced by a number of variables, such as the fractional urine flow rate [20], An influence of diuresis on urinary enzymuria also has been demonstrated [21], and has been shown to particularly affect the excretion of soluble forms [19] rather than that of particulate forms. The expression of urinary enzymatic activities as a ratio to urinary creatinine con centration, which has been used in this study, has been recommended to compensate the effects of diuresis as well as to simplify the col lection of urine samples from neonates and infants [21], In our study, the influence of cir cadian variations of enzymuria [22] should have been minimized by the constant time of urine collection, that of early morning.…”

Section: Discussionmentioning

confidence: 99%

“…Lysosomal and brush border enzyme production is considered to involve two separate mechanisms in proximal tubule cells; exocytosis and physiological membrane turnover, respectively. Brush border enzymu ria has been shown to exist in both a particu late form, which results from the shedding of fragments from the cellular membrane, and a soluble form, whose excretion in urine is in fluenced by the urine flow rate [19].…”

Section: Discussionmentioning

confidence: 99%

Specific Developmental Profiles of Lysosomal and Brush Border Enzymuria in the Human

Siméoni¹,

Schnitzler²,

Massfelder

et al. 1994

Neonatology

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Various enzymatic urinary activities have been proposed to assess renal proximal tubule damage in children, including neonates. Nevertheless comprehensive knowledge on the developmental aspects of physiological enzymuria is limited, particularly with regard to lysosomal and brush border enzymuria. Urinary activities of two lysosomal enzymes, N-acetyl-β-D-glucosaminidase (NAG) and β-galactosidase (GAL), and of two brush border enzymes, alanine aminopeptidase (AAG) and γ-glutamyltransferase (GGT) were comparatively investigated in normal prematures (n = 28), term neonates (n = 52), infants aged less than 2 years (n = 19) and children (n = 33), and compared to urinary excretion of β₂-microglobulin (B2M). Enzymatic activities were assayed using either spectrophotometrical (NAG, AAP, GGT) fluorimetrical (GAL) or radioimmunological (B2M) methods, and were related to urinary creatinine excretion. Developmental profiles of both the studied lysosomal enzymes and of B2M were similarly characterized with significantly decreasing values from prematures (NAG 9.29 ± 1.44, GAL 2.26 ± 0.26 IU/mmol creatinine, indicated as mean ± SEM) to term neonates (6,94 ± 0.58 and 1.76 ± 0.15 IU/ mmol creatinine, respectively) and older infants and children. Lysosomal enzymatic urinary activities correlated linearly with a coefficient of r = 0.75, (p < 0.05), while correlations between each lysosomal enzymatic activity and B2M urinary excretion were weaker. Profiles of both the studied brush border enzymes were characterized with lower activities in prematures (AAP 4.45 ± 0.44, GGT 5.52 ± 0.49 IU/mmol creatinine) than in term neonates (5.62 ± 0.92 and 9.1 ± 1.73 IU/mmol creatinine, respectively) or even in infants with respect to GGT (AAP 4.06 ± 0.72 and GGT 11.54 ± 1.71 IU/mmol creatinine), with a consecutive decrease of activities in older infants or children. It is concluded that lysosomal and brush border enzymuria follow different developmental profiles in the normal human. Studies involving enzymuria as a marker of tubular lesion should include the measurements of at least one lysosomal and one brush border enzymatic activity, and should be interpreted with reference to the respective, specific developmental profiles.

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Diuresis-dependent excretion of multiple forms of renal brush-border enzymes in urine

Cited by 16 publications

References 10 publications

Cell-Specific Biomarkers in Renal Medicine and Research

Cell-Specific Biomarkers in Renal Medicine and Research

A Diagnostic Programme for Quantitative Analysis of Proteinuria

Specific Developmental Profiles of Lysosomal and Brush Border Enzymuria in the Human

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