Glomerular atrial natriuretic factor receptors in primary glomerulopathies: studies on human renal biopsies

Human renal biopsies are currently used to provide information about morphologic changes, chronicity of disease, patterns of inflammation, and immunoglobulin deposition. This practice has provided only limited insight into functional aberrations and has failed to provided information necessary for disease classification based on pathophysiology. To expand the potential of the renal biopsy in this regard and to determine whether differences in glomerular atrial natriuretic factor (ANF) binding exist in different forms of primary renal disease, quantitative autoradiography and 125I-human ANF (1-28) were used to determine the location and pharmacological characteristics of ANF binding sites in the normal human kidney. Specific ANF binding was highest in the glomeruli, but lower levels of specific binding were localized to the inner medulla and the interlobular arteries. ANF binding sites in the human kidney were found to be highly stable and similar in both location and pharmacology to those observed in experimental animals. As determined by saturation experiments, the equilibrium dissociation constants for glomeruli, inner medulla, and interlobular arteries were almost identical at 4.0 x 10(-11) mol/L. Competitive binding inhibition studies with unlabeled human ANF (1-28) demonstrated highly specific binding shared by the glomerulus, inner medulla, and interlobular artery, with apparent half-maximal inhibition concentrations of 9.2 x 10(-10) mol/L, 8.0 x -10 mol/L, and 8.2 x 10(-10) mol/L, respectively. Quantitation of specific binding of ANF to glomeruli in needle biopsy specimens of three primary glomerulopathies, ie, minimal-change disease, membranous nephropathy, and focal glomerulosclerosis, showed no differences among the groups. This study demonstrates the feasibility of studying receptor physiology on biopsy specimens of the human kidney and should allow renal diseases, particularly of glomerular origin, to be characterized according to differences in hormone binding and hormone responsiveness. The absence of significant differences in glomerular ANF binding in the primary glomerulopathies studied is consistent with other studies that have failed to delineate important pathophysiological differences in renal function and volume homeostasis in these disease states.