PATTERNS OF TUBULAR PROTEINURIA FROM METALS AND SOLVENTS

Using modern technology, minute quantities of low-molecular-weight-proteins (LMWP), prostanoids, growth factors, and intrarenal and extrarenal enzymes can be measured in urine. Excretory patterns that are characteristic for the site and mechanism of renal injury often can be found. It is possible to recognize urinary biomarker patterns that suggest the putative environmental nephrotoxin. This fingerprinting approach has become an effective tool in recent years as urine from cohorts with known occupational nephrotoxin exposures has been analyzed for patterns of specific constituents in European cooperative studies. The authors' studies performed on subjects with occupational and environmental exposures in New Jersey confirm the pattern specificity and threshold effects for chromium, mercury and lead. In addition, they have been able to show that increased N-acetylglucosaminidase excretion following lead exposure correlates with current (blood lead) but not with cumulative (bone lead) exposure. The success of recent cooperative efforts has been in part due to the absence of clinical renal failure in study subjects. Urinary biomarkers indicate early renal injury. As renal failure progresses, excretory patterns become nonspecific. Moreover, renal injury that results in tubular proteinuria may not progress to renal failure. Nevertheless, biomarkers of renal injury can help establish acceptable exposure levels and identify the need for long-term surveillance to ascertain when clinical renal disease may result