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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.

Introduction: Beta 2 microglobulin (beta2M) is filtered by the glomeruli and reabsorbed by the proximal tubular cells where it is metabolized. Its plasma concentration increases with decreasing renal function., Aim: To compare serum creatinine (Cr) and serum beta2M as markers of GFR., Patients and Methods: In 160 adult patients, with various kidney diseases and different GFR, serum Cr (autoanalyzer), serum beta2M (RIA) and GFR (bladder cumulative method using 99mTc-DTPA as glomerular tracer) were measured in the same day., Results: A linear relationship was observed between In GFR and both In serum Cr (lnCr=3.112-0.716 lnGFR; r=0.92) and ln serum beta2M (lnbeta2M= 4.274-0.814 lnGFR; r = 0.90). With decreasing GFR the increase in serum beta2M was higher than that of serum Cr (see regression coefficients that are significantly different). The normal upper limit of serum Cr corresponds to a GFR 48.1 mL/min while that of serum beta2M to a GFR 65.0. With decreasing GFR the increase of serum beta2M occurs before than that of serum Cr., Conclusions: With declining renal function, serum beta2M increases more and before than serum Cr. Serum beta2M is a good endogenous marker of GFR, better than serum Cr.

Chromogranin A (CGA) is a low MW (49,000) acidic hydrophilic protein. It is synthesized in the chromaffm granules of the neuroendocrine cells, and has been found circulating in the blood of healthy subjects. The aim of this study was to assess the relationship between serum levels of CGA and renal function. One hundred two renal patients (45 M and 57 F; age 14-76 years, mean 52) participated in the study. Glomerular filtration rate (GFR) was measured by the bladder cumulative method, using 99mTc-DTPA as a tracer. Blood CGA was determined by RIA. Plasma creatinine, beta2microglobulin (beta2m) and tumor associated trypsin inhibitor (TATI) were also determined. The reduction in renal function was associated with an increase in all of the above studied parameters. In patients with advanced renal failure (GFR <20 mL/min) CGA levels increased by 22-fold as compared to the patients with normal renal function (GFR> 100 mL/min). The other studied parameters were also increased but to a lesser degree, e.g., TATI 14-, beta2m 8- and creatinine 5-fold. The results of this study demonstrate that renal handling of the CGA is similar to other low MW proteins, and it accumulates in the blood in renal failure.

The aim of this study was to evaluate the relationship between renal function and the blood level of some tumor markers that are low molecular weight proteins, that is, tumor-associated trypsin inhibitor (TATI), squamous cells carcinoma antigen (SCC), cytokeratin 19 fragments (CYFRA 21-1), tissue polypeptide antigen (TPA), and M3-specific epitope of tissue polypeptide antigen (TPS). In 41 adult patients without evidence of neoplastic disease, glomerular filtration rate (GFR) and the blood levels of creatinine and of the tumor markers were determined. The decrease in GFR was accompanied by an increase in serum levels of TATI, SCC, CYFRA 21-1, and TPA. The serum level of tumor markers increased particularly when GFR fell below 40 ml/min. On the basis of these results, the renal function must be taken into account for the clinical evaluation of the studied tumor markers.

Renal function was assessed in 20 (11 female and 9 male, age 21-76 years, mean 53) renal patients with a creatinine clearance 25-145 ml/min, mean 95, to evaluate the effects of iohexol, a non-ionic low-osmolar contrast medium. Intravenous urography was performed in 16 patients and computed body tomography in 4, using a dose of iohexol ranged between 0.6-3.3 (mean 1.17) g/kg b.w. Different parameters of renal function were determined in the week preceding and 1, 3 and 5 days after the administration of iohexol. The principal renal effect of iohexol was an increase of urinary alanine aminopeptidase, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-D-glucosaminidase. The maximum increase of enzymuria was observed on day 1 after the administration of iohexol. In most cases enzymes returned to base-line values within 3 days. No relevant variation of renal hemodynamics (glomerular filtration rate and effective renal plasma flow) was observed after iohexol. In conclusion, iohexol can increase of urinary enzymes, but the effect is rapidly reversible and is not accompanied by a clinically significant impairment of renal hemodynamics.