The specific proteinuria of cancer patients

Abstract

Most patients with disseminated cancer have proteinuria. Twenty-four hour urine protein averaged less than 80 mg in normals; 223 mg in patients with acute myelocytic leukemia; 177 mg in subjects with stage IV Hodgkin's; 215, 229, 233, and 280 mg in patients with metastatic cancer of colon, breast, ovary, and pancreas respectively. We recently purified the novel glycoprotein EDC1 (mol wt 27,000) from the urine of patients with several types of cancer and found it to be a fragment of plasma inter-alpha-trypsin inhibitor (IATI) (mol wt 170,000). Both EDC1 and IATI are antiproteolytic. By radial immunodiffusion and radioimmunoassay of the 41 recognized plasma proteins and of EDC1, we have now analyzed the composition of urine protein in: (i) five nephrotics ("glomerular proteinuria"), (ii) four patients with cystinosis and four with hereditary renal tubular acidosis ("tubular proteinuria"), and (iii) 26 proteinuria (200-800 mg/day) patients with the six types of disseminated cancer listed above. In (i), (ii) and (iii) the 41 plasma proteins accounted for 100%, greater than 95%, and 33-60% of the urine protein, respectively, while EDC1 accounted for less than 1%, less than 1%, and 40-63% respectively. In normals, (i), (ii) and (iii), plasma EDC1 averaged less than 1, less than 1, less than 1 and 65 micrograms/ml respectively. Renal clearance of EDC1 in (iii) averaged 3% of creatinine clearance. In three cancer patients with EDC1-proteinuria, postmortem renal histology was normal.

Conclusion: most types of cancer cell interact with plasma IATI 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.