EARLY URINARY MARKERS OF TARGET NEPHRON SEGMENTS AS STUDIED IN CADMIUM TOXICITY

A number of chemicals may adversely affect one or more of the anatomic al structures of the kidney, such as the glomerulus, the tubular appar atus, the medullary, or interstitial cells. To recognize subclinical r enal dysfunction, a battery of new, non-invasive tests was applied in comparison to established ones. The study on cadmium exposed subjects, performed within the framework of a collaborative European research p roject, exemplifies the concept of target selectivity within a nephron . One hundred seventy-two subjects were classified according to urinar y cadmium excretion as controls (<1.5 mu g/g creatinine), or subjects with moderate or high cadmium body burden (1.5 to 5 mu g/g creatinine, >5 mu g/g creatinine). Twenty-six urinary analytes (such as serum der ived proteins, tubular enzymes, eicosanoids) and four plasma markers, related to the function or integrity of specific nephron segments, wer e investigated in a cross-sectional study. The group with the moderate cadmium body burden showed alterations of proximal tubular integrity, that is, increased excretion of tubular brush-border antigens. The gr oup with higher cadmium body burden revealed an involvement of the who le nephron. The most prominent quantitative changes were found for the glomerular markers high molecular weight proteins, and thromboxane B- 2 and for the proximal tubular markers retinol binding protein, alpha( 1)-microglobulin, N-acetyl-beta-D-glucosaminidase, and the intestinal alkaline phosphatase. A diagnostic approach to screen for nephrotoxici ty due to environmental hazards like cadmium should include proximal t ubular markers (alpha(1)-microglobulin and tubular enzymes, that is, i ntestinal alkaline phosphatase) but the measurement of glomerular mark ers is also advisable.