Suppression of Para-aminohippurate Transport in the Isolated Perfused Kidney by an Inhibitor of Protein Binding in Uremia

Abstract

Serum from patients with advanced renal failure contains substances that inhibit binding of small ligands to albumin. The extractable inhibitors of binding to albumin (lx), which were previously shown in rat kidney slices to inhibit para-aminohippurate (PAH) transport, were added to the in vitro perfused rat kidney in an attempt to investigate effects on organic acid transport in the intact organ. Following addition of extract to the perfusate there was an immediate and profound decrease in whole kidney PAH secretion. Mean PAH clearance fell an average of 60% +/- 7% after addition of extract from human uremic pleural exudate and an average of 62% +/- 6% after addition of similarly prepared extract from normal human urine. There was no change in inulin clearance, vascular resistance, urine flow, or fractional reabsorption of sodium. The effect was shown to be as marked when bovine serum albumin (4.0 g/dL) was added to the perfusate, clearances falling 66% +/- 7%. Controls showed no change in PAH or inulin clearance during 90 minutes of in vitro perfusion. An increase in ultraviolet (UV) absorbance by the urine within minutes after addition of inhibitor to the perfusate suggested tubular secretion of a major portion of the extract. Partial recovery of PAH clearance was observed after 20 to 40 minutes in most kidneys and near complete recovery occurred in some kidneys. The inhibitory effect was duplicated by addition of hippurate at 24 mg/dL (1.2 mmol/L) to the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)