Proteinuria with Disseminated Neoplastic Disease1

Low-grade proteinuria occurs in most patients with dis seminated cancer. Twenty-four-hr urine protein (average ± S.D.; N = 9 to 17) was <80 mg in normals; 223 ±154 mg in patients with acute myelocytic leukemia; 177 ±98 mg in subjects with Stage IV Hodgkin's; and 215 ±147, 229 ± 186, 233 ±163, and 280 ±240 mg in patients with meta static cancer of colon, breast, ovary, and pancreas, respec tively. The novel glycoprotein EDC1 (M.W. 27,000) was isolated previously from the urine of patients with several types of cancer and shown to be a fragment of plasma inter a-trypsin inhibitor (M.W. 170,000). Both EDC1 and inter-ct trypsin inhibitor inhibit the serine proteases trypsin and chymotrypsmn. By radial immunodiffusion and radioimmu noassay of the 41 recognized plasma proteins and of EDC1, the composition of urine protein has now been analyzed in: (a) five nephrotics (glomerular proteinuria); (b) four patients with cystinosis and four with hereditary renal tubular aci dosis (tubular proteinuria); and (c) 26 proteinuric (200 to 800 mg/day) patients with the six types of disseminated cancer listed above. In a, b, and C, the 41 plasma proteins accountedfor100%,>95%, and 33 to60% oftheurine protein , respectively, whereas EDC1 accounted for <1%, <1%, and 40 to 63%, respectively. In normals, a, b, and c, plasma EDC1 averaged <1 , <1 , <1 , and 65 @g/ml,respec tively. Renal clearance of EDC1 in c averaged 3% of creati nine clearance. Postmortem renal histology in three cancer patients with EDC1 proteinuria was normal. Our conclusion is that most types of cancer cells interact with plasma inter a-trypsin inhibitor to generate plasma EDC1 which is rapidly filtered by the glomeruli, with a resultant “overflow― or “prerenal― proteinuria, which is unique to disseminated neoplastic disease.