1. Fractional excretions of pepsinogens A and C in the urine were investigated in 21 healthy subjects and in 38 patients with chronic renal insufficiency. In eight of the healthy subjects fractional excretions were measured again after oral administration of omeprazole for 9 days.
2. The mean fractional excretion of pepsinogen A was 27.6% (range 4.4–73.9%) in healthy subjects and remained unchanged after omeprazole administration. In patients with renal failure the mean fractional excretion of pepsinogen A was 37.9% (range 7.0–81.9%). The mean fractional excretion of pepsinogen C was 1.0% (range 0.04–6.8%) in healthy subjects and decreased after omeprazole. In patients with chronic renal diseases a sharp rise in fractional excretion of pepsinogen C was observed once glomerular filtration rate was less than 40 ml/min.
3. Fractional excretion of pepsinogen A was unexpectedly high for a negatively charged protein with a molecule mass of 40 000 daltons. This might be explained by the presence of the positively charged activation peptide. Furthermore, pepsinogen C seemed to be almost entirely reabsorbed from the glomerular filtrate and a tubular reabsorption maximum appeared to be present. Pepsinogen C may, therefore, be a new marker of tubular function. The cause of the remarkable difference in tubular handling of two quite similar low-molecular-mass proteins remains to be elucidated.