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Titolo:
HUMAN INTESTINAL VERSUS TISSUE-NONSPECIFIC ALKALINE-PHOSPHATASE AS COMPLEMENTARY URINARY MARKERS FOR THE PROXIMAL TUBULE
Autore:
NOUWEN EJ; DEBROE ME;
Indirizzi:
UNIV ANTWERP,DEPT NEPHROL,WILRIJKST 10 B-2650 EDEGEM BELGIUM
Titolo Testata:
Kidney international
, , anno: 1994, supplemento:, 47
pagine: 43 - 51
SICI:
0085-2538(1994):<43:HIVTAA>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUSTRIAL POLLUTANTS; INORGANIC MERCURY; LEAD NEPHROPATHY; RENAL-FUNCTION; KIDNEY; RATS; LOCALIZATION; SEGMENT; CADMIUM; NEPHROTOXICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
64
Recensione:
Indirizzi per estratti:
Citazione:
E.J. Nouwen e M.E. Debroe, "HUMAN INTESTINAL VERSUS TISSUE-NONSPECIFIC ALKALINE-PHOSPHATASE AS COMPLEMENTARY URINARY MARKERS FOR THE PROXIMAL TUBULE", Kidney international, 1994, pp. 43-51

Abstract

The availability of early biological markers of renal damage is important for the identification of risk factors and for starting therapeutic intervention in the reversible phase of renal pathology. The usefulness of such markers relies upon their capacity to detect alterations in distinct nephron segments. Using specific monoclonal antibodies against the intestinal isoenzyme of alkaline phosphatase (IAP) and against the tissue-nonspecific isoenzyme (TNAP), we demonstrated that IAP expression in the human kidney is restricted to the straight part of theproximal tubule (the S3 segment), whereas TNAP is expressed mainly inthe proximal convoluted tubule (the S1 and S2 segments) but also in the S3 segment. This complementarity opens perspectives for IAP and TNAP as distinct proximal tubular markers, particularly for IAP, since there are no other markers available that are specific for the S3 segment. Based on these monoclonal antibodies, specific and easy to use enzyme-antigen immunoassay (EAIA) procedures were developed to detect IAP and TNAP in human urine samples. The detection limits are below the lowest enzyme activities found in the urine of normal subjects, the intra- and inter-assay variability is low, the analytical recovery approaches 100%, and EAIA enzyme activity values correlate with ELISA immunoreactivity values. Furthermore, easy urine sample preconditioning allows antigen preservation over an extended time period at 4 degrees and -80 degrees C. Using these assays, it could be demonstrated in more than 20 occupationally and environmentally exposed cohorts and clinical patient groups that urinary IAP is indeed a marker of early alterationsin the 83 segment, and that it behaves largely independently from urinary TNAP. Workers occupationally exposed to mercury vapor presented asignificantly higher excretion of IAP but not TNAP than controls. IAPexcretion was also increased in workers displaying urinary cadmium levels above the biological exposure limit of 5 mu g/g creatinine, whereas TNAP was elevated only at higher exposures. In incipient diabetes mellitus, urinary IAP, but not TNAP, was elevated; part of this increase was unrelated to differences in glycated hemoglobin, indicating thatvery early changes occur in the highly sensitive 83 segment independent of the degree of metabolic control of diabetes. Finally, IAP and TNAP remained within normal values in all appropriate control populations studied. In conclusion, LAP and TNAP have an interesting potential as urinary markers with complementary specificity to screen for nephrotoxic effects at the level of the proximal tubule, resulting from either environmental, occupational, or therapeutic exposure to hazardous substances, or from incipient diabetes mellitus. Their predictive Value remains to be established.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 18:55:10