Decreased urinary peptide excretion in patients with renal disease

Background Normal urine contains low-molecular-weight peptides or protein fragments that have been poorly studied, primarily because of the technical difficulty of measuring peptides in the presence of proteins. We studied these substances in healthy subjects and patients with renal disease and varying degrees of proteinuria to understand the factors that determine their excretion. Methods: We estimated these substances as the difference between results using the Lowry method (which detects both proteins and peptides) and those obtained using the dye-binding Bradford (Biorad) method (Biorad Laboratories Inc, Hercules, CA; which detects only proteins). Results: We validated this 2-assay approach to measure peptide levels by showing that such proteins as immunoglobulin G, albumin, and lysozyme were measured equally by the Lowry and Biorad methods, whereas degraded proteins were recognized by the Lowry method only, but not by the Biorad method. We found that healthy subjects excreted less than 200 mg of protein, but 3 to 4 g of peptides/g creatinine; thus, peptides constituted approximately 95% of total protein material excreted in urine. Patients with renal disease and proteinuria had a progressive decrease in peptide excretion, ranging from 3 to 0 g/g creatinine. Twenty-five percent of nephrotic patients (118 of 72 patients) excreted very small amounts of peptides in urine (0% to 10% of total protein material). Conclusion: We found that healthy persons excrete substantial amounts of peptides in urine, and this excretion decreases in the presence of proteinuric renal disease. It is possible that these peptides in urine arise from the tubular degradation of filtered proteins and exocytosis of protein fragments toward the urinary side, a process that becomes increasingly impaired as proteinuria increases.