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.

C-reactive protein and interleukin-6 levels are related to renal function in predialytic chronic renal failure.

BACKGROUND: Several studies have provided convincing evidence that in apparently healthy subjects elevated serum levels of plasma C-reactive protein (CRP) are associated with an increased risk of experiencing myocardial infarction and sudden cardiac death. It has been claimed that, in dialytic patients, the hepatic synthesis of this 'acute phase response' plasma protein is primarily induced by the macrophage-derived interleukin 6 (IL-6). Little information is available, however, regarding CRP and IL-6 plasma levels in pre-dialytic renal failure. METHODS: Plasma CRP by a modification of the laser nephelometry technique, IL-6 and serum albumin were determined in 103 chronic pre-dialytic patients (mean age 50 +/- 6.3 years; creatinine clearance (Cr.cl.) 36.3 +/- 23.1 ml/min). RESULTS: CRP was >5 mg/l (normal upper range) in 42% of the global population. CRP and IL-6 were significantly related (r = 0.35, p < 0.0004). CRP and IL-6 were related to renal function (CRP vs. Cr.cl., r = -0.56, p < 0.0001; IL-6 vs. Cr.cl., r = -0.55, p < 0.0001, Spearman correlation coefficient). When patients were divided in tertiles according to renal function, CRP median value resulted 7.9 mg/l (interquartile interval: 5-12) in the first tertile (Cr.cl. <18.5 ml/min), 4.0 mg/l (3-6) in the second tertile (Cr.cl. 18.5-45 ml/min) and 3.2 mg/l (2.7-4.0) in the last tertile (Cr.cl. >45 ml/min) (p < 0.0001). A negative correlation between CRP and S-albumin was also found (r = -0.52, p < 0.0001, Spearman correlation coefficient). CONCLUSIONS: IL-6 and CRP were increased and were inversely related to creatinine clearance in our population of 103 chronic predialytic patients. The possibility of a decreased renal clearance of CRP and/or cytokines as a cause of an activated acute-phase response is discussed. A negative correlation between CRP and S-albumin was found confirming the link between chronic inflammation and malnutrition in chronic renal patients.