Determination of Clara cell protein urinary elimination as a marker of tubular dysfunction

Abstract

Clara cell 16-kDa protein (CC16) is a protein expressed primarily by the bronchial cells. It is rapidly eliminated by glomerular filtration, reabsorbed almost entirely, and catabolized in proximal tubule cells. To date, normal values for urinary CC16 in healthy children have not been determined. We have studied 63 pediatric patients (mean age 8.17 +/- 3.91 years) and 31 healthy children (control group; mean age 8.83 +/- 3.65 years). In the control group, the CC16/creatinine ratio was 1.22 +/- 1.52 microg/g. In 16 out of 31 control children, the value of the ratio was zero. Fourteen patients (22.2%) showed a high CC16/creatinine ratio; in contrast, among these same patients, the ratio N-acetyl-beta-D: -glucosaminidase (NAG)/creatinine was elevated in seven cases (11.1%) and the ratio beta2-microglobulin/creatinine was elevated in seven cases (11.1%). The three parameters were in agreement in 51 patients (80.9%). Among the patients, the CC16/creatinine ratio was correlated with both the beta2-microglobulin/creatinina ratio (r = 0.76, P < 0.001) and the NAG/creatinine ratio (r = 0.6, P < 0.001). Our findings indicate that CC16 is a good marker of proximal tubular function in childhood. The highest observed values were in children with proximal tubulopathies, in children with chronic renal failure, and in those treated with cyclosporine.

Association of Children’s Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media

“…Even though, after adjustment for specific gravity, we had a log-normal distribution of concentrations, assigning all of these censored data the same value, likely decreased the power of our analysis. The urinary levels of CC16 in our study are within the range of what has been reported in the few other studies that have measured CC16 in healthy children’s, as well as in asthmatic children’s, urine [ 14 , 46 , 47 ]. In the future, studies should use an ELISA kit with a lower limit of detection, as was recently reported by Ma and colleagues [ 14 ].…”

Urine proteome analysis by C18 plate–matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allows noninvasive differential diagnosis and prediction of diabetic nephropathy

“…Dysfunction of the proximal tubule cells can cause diminished resorption of CC16 and its increased levels in urine. CC16 has been reported as a marker of proximal tubular dysfunction in adult [ 26 ] and child patients [ 27 ]. This protein marker is sensitive to very subtle defects in proximal tubular dysfunction that may not be detected by assay of classical urinary low-molecular-weight proteins [ 28 ].…”

Normal Levels of Urinary CC16 Protein. Comments on Beamer et al. Association of Children’s Urinary CC16 Levels with Arsenic Concentrations in Multiple Environmental Media. Int. J. Environ. Res. Public Health 2016, 13, 521.

“…Therefore, in our first paper on the subject, the value of the urinary CC16-to-creatinine ratio was zero in 16 of the 31 control children (51.6%) [12]. In another recent study by our group [13], the average urinary CC16-to-creatinine ratio in control children (1.12 ± 0.59 μg/g) ( n = 28) was even lower than that in the first study (1.22 ± 1.52 μg/g).…”