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

作者: Thomas A. Depner , Tsutomu Sanaka , Linda A. Stanfel

DOI: 10.1016/S0272-6386(84)80046-3

关键词: KidneyEndocrinologyPAH clearanceInternal medicineAminohippuric acidOrganic acid transportUremiaInulin ClearanceSerum albuminBovine serum albuminMedicineBiochemistry

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

参考文章(19)
Roger H. Bowman, Methodology for Study of Isolated Perfused Rat Kidney in Vitro Springer, Boston, MA. pp. 385- 399 ,(1978) , 10.1007/978-1-4615-8894-8_15
JM Nishiitsutsuji-Uwo, BD Ross, HA Krebs, Metabolic activities of the isolated perfused rat kidney Biochemical Journal. ,vol. 103, pp. 852- 862 ,(1967) , 10.1042/BJ1030852
W Cathcart-Rake, R Porter, F Whittier, P Stein, M Carey, J Grantham, Effect of diet on serum accumulation and renal excretion of aryl acids and secretory activity in normal and uremic man The American Journal of Clinical Nutrition. ,vol. 28, pp. 1110- 1115 ,(1975) , 10.1093/AJCN/28.10.1110
T.H. Steele, B.A. Stromberg, J.L. Underwood, Inhibitory Action of Urate on p-Aminohippurate Secretion by the Isolated Rat Kidney Nephron. ,vol. 31, pp. 266- 269 ,(1982) , 10.1159/000182657
Marcus M. Reidenberg, Ingegerd Odar-Cederlöf, Christer von Bahr, Olof Borgå, Folke Sjöqvist, Protein Binding of Diphenylhydantoin and Desmethylimipramine in Plasma from Patients with Poor Renal Function The New England Journal of Medicine. ,vol. 285, pp. 264- 267 ,(1971) , 10.1056/NEJM197107292850506
Thomas A. Depner, Suppression of tubular anion transport by an inhibitor of serum protein binding in uremia Kidney International. ,vol. 20, pp. 511- 518 ,(1981) , 10.1038/KI.1981.169
Thomas A. Depner, Linda A. Stanfel, Elizabeth A. Jarrard, Paul F. Gulyassy, Impaired Plasma Phenytoin Binding in Uremia Nephron. ,vol. 25, pp. 231- 237 ,(1980) , 10.1159/000181845
Jared J. Grantham, Richard L. Irwin, Patti B. Qualizza, Donald R. Tucker, Frederick C. Whittier, Fluid Secretion in Isolated Proximal Straight Renal Tubules EFFECT OF HUMAN UREMIC SERUM Journal of Clinical Investigation. ,vol. 52, pp. 2441- 2450 ,(1973) , 10.1172/JCI107435
Peter C. Farrell, Frank A. Gotch, John H. Peters, Bernard J. Berridge, jr., Maryann Lam, Binding of hippurate in normal plasma and in uremic plasma pre- and postdialysis. Nephron. ,vol. 20, pp. 40- 46 ,(1978) , 10.1159/000181194
Thomas A. Depner, Paul F. Gulyassy, Linda A. Stanfel, Elizabeth A. Jarrard, Plasma protein binding in uremia: Extraction and characterization of an inhibitor Kidney International. ,vol. 18, pp. 86- 94 ,(1980) , 10.1038/KI.1980.113