Assessment of tumor-associated trypsin inhibitor (TATI) as a marker of renal function

J Nephrol. 2003 Sep-Oct;16(5):663-72.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Biomarkers / blood
  • Creatinine / blood
  • Female
  • Glomerular Filtration Rate*
  • Humans
  • Iodine Radioisotopes
  • Kidney / metabolism
  • Male
  • Middle Aged
  • Radiopharmaceuticals
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency / diagnosis
  • Technetium Tc 99m Pentetate
  • Trypsin Inhibitor, Kazal Pancreatic / blood*
  • Trypsin Inhibitor, Kazal Pancreatic / metabolism
  • beta 2-Microglobulin / blood

Substances

  • Biomarkers
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • beta 2-Microglobulin
  • Trypsin Inhibitor, Kazal Pancreatic
  • Creatinine
  • Technetium Tc 99m Pentetate