Handling of human pepsinogens by the isolated rat kidney: evidence for a high glomerular sieving coefficient

Pepsinogen A (PGA) and pepsinogen C (PGC) are low-molecular-weight proteins synthesized by the gastric mucosa. Data in man suggest that both pepsinogens are almost freely filtered through the glomerular basement membrane despite a molecular weight of about 43,000 dalton and a strongly negative charge. This promoted us to investigate the glomerular sieving of PGA and PGC in the isolated rat kidney model by measuring their fractional excretions before and after inhibition of tubular function with sodium iodoacetate. During the control episode fractional excretion of PGA was 40 +/- 0.04% and of PGC 42 +/- 0.04% (mean +/- SEM from 9 experiments). After complete inhibition of tubular function a large increase in fractional excretion was found for both pepsinogens: 87 +/- 0.04% for PGA and 95 +/- 0.09% for PGC. It is concluded that tubular secretion does not contribute to the high fractional excretion of pepsinogens and that both PGA and PGC are almost freely filtered through the glomerular basement membrane.