GASTRIN PROCESSING AND SECRETION IN PATIENTS WITH END-STAGE RENAL-FAILURE

Gastrin circulates at higher than normal concentrations in patients wi th end-stage renal failure (ESRF). However, it remains unclear which f orms of gastrin are elevated and whether there is also an alteration i n the secretory profile after stimulation. In the present study all pr ocessed and partially processed forms of circulating gastrin were meas ured in plasma before and after meal stimulation in ESRF patients and control subjects. Since Helicobacter pylori (HP) infection affects gas trin secretion, HP status was determined. Fasting gastrin-amide (36 +/ - 8 pmol/L), gastrin-Gly (55 +/- 16 pmol/L), and total gastrin (218 +/ - 32 pmol/L) measured in ESRF/HP-patients were all significantly great er than those in the control group (10 +/- 1, 15 +/- 3, and 17 +/- 2 p mol/L, respectively; P < 0.01). Plasma gastrin-amide (126 +/- 67 pmol/ L) and total gastrin (397 +/- 164 pmol/L) were highest in the ESRF/HP patients. The proportion of nonamidated gastrin products was 4-fold h igher in ESRF patients than in control subjects, suggesting structure- specific changes in gastrin secretion and metabolism, and this was con firmed by chromatography. The meal-stimulated increments in control/HP - and ESRF/HP-groups were similar. However, the ESRF/HP+ group had a m arkedly potentiated gastrin response. Pasting plasma somatostatin, an inhibitor of gastrin secretion, was also measured and was significantl y lower in the ESRF patients than that in the control group. These stu dies show that the hypergastrinemia associated with renal failure has been underestimated. This is because only amidated products were measu red. The potentiated gastrin meal response in ESRF attributed previous ly to changes in gastrin metabolism are in part explained by the effec t of HP infection. The observed diminished somatostatin response sugge sts that the increase in circulating gastrin in ESRF is the result of loss of inhibition of secretion as well as decreased metabolism. As bo th amidated and nonamidated gastrin are now considered to have trophic and secretory effects, these findings may explain the gastrointestina l tract hypertrophy often associated with ESRF.