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Background: Proteinuria is a risk factor for end-stage renal disease (ESRD). Creatinine clearance (CrCl) is usually used as a marker to monitor the progression of ESRD, while cystatin C (CYST) has also been considered as a marker of renal function. Tumor-associated trypsin inhibitor (TATI) has been shown to be a promising marker of renal function. The aim of this study was to examine the relationship between CrCl, CYST, ß(2)-microglobulin (B2M) and TATI, with glomerular filtration rate (GFR) in patients with different levels of proteinuria., Methods: Seventy-one patients (37 males, 34 females, mean age 53 ± 15 years) were included in the study. GFR was measured by the bladder cumulative method using (99m)Tc-DTPA. Blood levels of CYST, B2M and TATI were also measured. CrCl and proteinuria were determined by 24-hour urine collection. Statistical analysis was performed with multivariate analysis., Results: The results are expressed as the ratio to GFR of CrCl and reciprocals of CYST (100/CYST), B2M (100/B2M) and TATI (100/TATI). The ratio CrCl/GFR increased from 1.41 in patients with proteinuria <1 g/day, to 1.66 (p<0.05) in those with proteinuria >3 g/day. The ratio 100/CYST/GFR was 1.67 and 2.28 (p<0.05), 100/B2M/GFR 0.90 and 0.69 and 100/TATI/GFR 0.14 and 0.19, respectively. Multivariate analysis demonstrated that ClCr/GFR as well as 100/CYST/GFR was independently related to the degree of proteinuria., Conclusions: CrCl and CYST overestimate GFR in patients with heavy proteinuria, while the ratios 100/TATI and 100/B2M with GFR do not significantly change. The direct measurement of GFR still remains the best method to assess the progression of renal damage in patients with heavy proteinuria.

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.

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.

TATI (tumor associated trypsin inhibitor) is a low molecular weight protein employed as a tumor marker. To evaluate the role of the kidney in the clearance of TATI, we studied the rat kidney uptake of 125I-TATI. Total body scan demonstrated a high radioactivity in the kidneys of the rats and none in other organs. The relationship between serum TATI and glomerular filtration rate (GFR) was studied in man. For comparison serum beta 2-microglobulin (beta 2M) arid plasma creatinine were also determined. The decrease in GFR was accompanied by an increase in the other parameters. Serum TATI increased in patients with renal failure (GFR < 20 mL/min) 12.4 times with respect to subjects with normal renal function (p < 0.001, non-parametric Mann-Whitney test), beta 2M increased 7.6 times (p < 0.001) and creatinine 4.7 times (p < 0.001). The increase in TATI is statistically significant already in patients with GFR 60-40 mL/min (p < 0.005). These results suggest that TATI is handled by the kidney. It is a sensitive marker of reduction in renal function.

Tumor-associated trypsin inhibitor (TATI) is a low molecular weight protein employed as tumor marker. To evaluate the role of the kidney in the clearance of TATI we studied the relationship of serum TATI with the glomerular filtration rate (GFR), and for comparisons the relationships of beta 2-microglobulin (beta(2m)) and creatinine with GFR. Urine excretion and renal extraction of TATI were also determined. The decrease in GFR was accompanied by an increase in blood levels of TATI, beta(2m) and creatinine. Serum TATI increased 12.4 times in patients with renal failure (GFR < 20 ml/min) with respect to subjects with normal renal function (P < 0.001, non-parametric Mann-Whitney test), while beta(2m) increased 7.3 times (P < 0.001) and creatinine 4.7 times (P < 0.001). In patients with GFR 60 to 40 ml/min, only the increase in TATI was statistically significant (p < 0.005). Renal excretion of TATI was low but it increased progressively in renal failure. Renal extraction ranged from 13% to 41%, for a mean 24.87. These results suggest that TATI is handled by the kidney and that it is a snesitrive marker of reduction in renal function.