Urinary protein 1 or Clara cell protein: a new sensitive marker of proximal tubular dysfunction

Protein 1 or Clara cell protein (CC16) is a 16 kD protein secreted predominantly by Clara cells in terminal bronchioles and from puberty on in the male urogenital tract. The sensitivity of CC16 in urine as an index of proximal tubule dysfunction was compared to that of retinol-binding protein, beta 2-microglobulin and alpha 1-microglobulin. These microproteins were measured by latex immunoassay in the urine from 114 pregnant women, 126 diabetics (65 men and 61 women), 80 workers exposed to cadmium (36 men and 44 women), and from healthy subjects matched for age and sex. In women, CC16 appeared consistently as a much more sensitive index of tubular dysfunction than other microproteins. In female diabetics, for instance, the prevalence of elevated values of CC16 in urine (53%) largely exceeded that of other microproteins (< 30%) and even of albumin (35%). In men, however, the existence of a post-renal secretion contaminating the urine limits the sensitivity of CC16 which was revealed to be higher than that of other microproteins, in diabetics only. The assay of urinary CC16 has the potential, especially in women, to detect very subtle defects of the proximal tubule which pass completely unseen with other microproteins. We postulate that this unique sensitivity of CC16 is due to its very low concentration in tubular fluid which, combined with its anionic character, strongly hinders its access to brush border binding sites.