NEPHRON TARGET SITES IN CHRONIC EXPOSURE TO LEAD

With established urinary markers of kidney integrity the early renal e ffects of lead have previously been considered to be mainly tubular or tubulointerstitial. In a cross-sectional study on 81 male lead-expose d workers and 45 age-matched controls (median blood lead concentration s 2.03 and 0.34 mu mol/l respectively) not only well-established but a lso new urinary markers of renal integrity preferentially or exclusive ly located along the different nephron segments were analysed. Markers related to the glomerulus were 6-keto-prostaglandin(1 alpha), thrombo xane B-2, mainly produced in the glomerulus, and the extracellular mat rix protein fibronectin. Markers of the proximal tubule were the brush -border antigens BBA, BB50, and HF5 and the intestinal alkaline phosph atase. Prostaglandin E(2) and F-2 alpha, preferentially synthesized in the collecting duct and medullary interstitial cells, served as marke rs of these more distal nephron segments. In contrast to previous stud ies on the early phase of lead nephrotoxicity, not only tubular but al so glomerular involvement could be shown in the study presented here b y increases in the median values of 6-keto-prostaglandin(1 alpha), and decreases in fibronectin. The proximal tubular markers intestinal alk aline phosphatase and BBA confirmed that this particular segment of th e nephron is affected by lead. Effects on the collecting tubule or med ullary interstitial cells could also be observed. It is concluded that lead affects both the glomerulus and the tubular apparatus and that c ombinations of new and established markers could be valuable for a bet ter definition and early detection of lead nephropathy.