Toxic wastes and kidney disease: research needs.

In 1981 over one billion dollars will be spent sustaining the lives of patients with end-stage renal disease by hemodialysis and renal transplantation, but less than 0.02% of this amount will be invested in studies of nephrotoxicity (1). Any knowledge of the effect of industrial waste on human kidney disease gained from this miniscule effort will probably be serendipitous. Our monumental ignorance of this subject appears to have two sources. First, research on nephrotoxicity is largely confined to acute, high-dose exposure in animals; the delayed effects of chronic low-dose exposure in man remain virtually unexplored. Second, the etiology of most chronic kidney diseases in man is unknown. The diagnostic categories commonly used for end-stage renal diseases rarely stipulate underlying causes. Roughly 60% of dialysis and transplant patients are reported to have glomerulonephritis or interstitial nephritis. These two entities encompass most acquired chronic renal diseases. Yet methods for determining etiology are rudimentary, arbitrary or applicable only in a few highly specialized research laboratories. In addition, the standard clinical techniques for detecting renal disease, irrespective of etiology, have been improved little in sensitivity or specificity since they were described by Richard Bright 150 years ago. Chronic glomerulonephritis is usually detected by the presence of albuminuria, while renal failure is detected by elevations of the blood urea nitrogen (BUN) or serum creatinine (Scr). Unfortunately, proteinuria is characteristically absent in the early phases of interstitial nephritis and azotemia is not apparent until more than two-thirds of kidney function is lost. Consequently, toxin-induced chronic interstitial nephritis which is characterized in its early phases by the absence of albuminuria cannot usually be detected