Assessment of tumor-associated trypsin inhibitor (TATI) as a marker of renal function.
BACKGROUND
Low molecular weight (LMW) proteins have been proposed for renal function assessment. This study aimed to ascertain the usefulness of tumor-associated trypsin inhibitor (TATI), a LMW protein (6.200 d), as a glomerular filtration rate (GFR) marker. The results were compared with those of beta2-microglobulin and of creatinine (Cr).


METHODS
Renal handling of TATI labelled with 125I was first studied in rats. Then, in 198 patients, serum TATI levels and GFR (99mTc-DTPA clearance, bladder cumulative method) were determined. To evaluate urine excretion, the fractional TATI clearance was determined in 63 patients.


RESULTS
In rats, total body scan showed a large amount of radioactivity in the kidneys, but not in other organs. The duration of radioactivity demonstrated a peak-time of 11 min. In human beings, the relationship between TATI and GFR was similar to that of beta2-microglobulin and Cr. The increase in TATI with declining renal function was statistically significant, vs. patients with GFR > 100 mL/min, already in the group with GFR 80-100 mL/min (p < 0.05, Bonferroni-Dunn test). The beta2-microglobulin increase was significant in the group with GFR 60-80 mL/min and of Cr in the group with GFR 40-60 mL/min. In patients with renal failure (GFR < 20 mL/min) TATI increased, vs. patients with GFR > 100 mL/min, 13x, beta2-microglobulin 8x and Cr 5x. Urinary excretion of TATI, expressed as fractional clearance, was very low increasing when GFR fell < 40 mL/min.


CONCLUSIONS
The kidney plays an important role in the handling of TATI. When GFR fell, the increase in blood levels of TATI was sooner and higher than that of beta2-microglobulin and CR. Consequently, TATI can be added to the group of renal function markers.
Tramonti
Gianfranco
G
Department of Internal Medicine, Nephrology Unit, University of Pisa, Pisa, Italy. g.tramonti@med.unipi.it
Ferdeghini
Marco
M
Annichiarico
Carmela
C
Donadio
Carlo
C
Norpoth
Maria
M
Mantuano
Emanuela
E
Bianchi
Claudio
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000175:diagnosis; D016284:Technetium Tc 99m Pentetate; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000097:blood* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000097:blood
D015415:Biomarkers; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D001613:beta 2-Microglobulin; D014359:Trypsin Inhibitor, Kazal Pancreatic; D003404:Creatinine; D016284:Technetium Tc 99m Pentetate