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.
Tumour-associated trypsin inhibitor (TATI) is a low molecular weight (MW) protein employed as a tumour marker. The blood levels of some low MW proteins increase in renal insufficiency. The aim of this study is to evaluate the relationship between serum TATI and glomerular filtration rate (GFR). Serum beta 2-microglobulin (beta 2M) and plasma creatinine were also determined. The decrease of GFR was accompanied by an increase in the other parameters. The maximum increase of TATI was from a mean basal value of 8.51 +/- 5.58 micrograms l-1 in subjects with normal renal function to 107.27 +/- 63.34 micrograms l-1 in patients with renal failure; beta 2M increased from 1.45 +/- 0.38 to 11.16 +/- 5.73 mg l-1 and creatinine from 1.05 +/- 0.17 to 5.07 +/- 1.93 mg dl-1. The increase in TATI occurs sooner and is greater than that of beta 2M and of creatinine. These results suggest that TATI is handled by the kidney. It is sensitive marker of reduction in renal function. When TATI is used as a tumour marker, renal function must be taken into account in the evaluation of the results.
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.
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