[Studies of a connection between the maximum tubular transport for para-aminohippuric acid glucose in children with kidney diseases].
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Glomerular perm selectivity can be approximately estimated from the apparent glomerular protein clearance in terms of molecular weight since the relative protein clearance is approximately identical with the corresponding screen coefficient relation. Systematic relativization of individual protein clearances by reference to albumin (or transferrin) clearance requires the application of special calculations to find out the regression coefficients relevant to functional diagnosis. A PAH load influences tubular protein reabsorption so that the clearance of higher-molecular proteins (IgA alpha 2-macroglobuli, IgM) rises. Taking the changes in protein clearance under renotubular PAH load into account allows a more precise estimation of glomerular permeability to be made, in comparison with protein analyses not using PAH load.
A procedure is described for the synthesis of p-[(bisacarboxymethyl)aminomethyl carbamino] hippuric acid (PAHIDA). The compound was identified by i.r. and NMR spectroscopy. A lyophilized complex was prepared and labeled with 99mTc. The purity of the preparation is better than 98%. The stability of the 99mTc-PAHIDA complex is achieved 8 h after labeling. Biodistribution tested on white rats shows a maximum accumulation in kidneys of 6-10% within 2 min after injection, while the accumulation in the liver is 2-4% of the administrated dose. Preliminary clinical studies of 99mTc-PAHIDA on patients and its comparison with 131I-hippuran showed that the 99Tc-PAHIDA preparation has excellent characteristics for visualization of kidneys. However, it has slightly slower urinary elimination compared to hippuran, which it makes possible to use PAHIDA as a replacement of hippuran to a certain extent.
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Material injected into the cerebral ventricles can leave the cerebrospinal fluid (CSF) but remain in the cranial cavity. To analyze the disappearance of 3H- and of 14C-labelled material from the cranial cavity, such material was injected into the lateral ventricles together with a bulk flow marker, labelled with the other radionuclide. In the present pilot study 3H-PAH and 14C-inulin were used. Five microliter of a mixture was injected into each lateral cerebral ventricles in rats, which were killed at various intervals. The whole skull was analyzed without opening the CSF space after homogenization in the deep-frozen state. The samples were combusted and analyzed by liquid scintillation counting. Probenecid, injected intraperitoneally, inhibited the removal of 3H-PAH from the skull cavity, as anticipated. Immediately after the intraventricular injection, however, 3H-PAH was transiently retained, probably by uptake into actively transporting tissue. After injection of probenecid, this delay in removal was reduced. The difference in disappearance rate between 3H-PAH and 14C-inulin was estimated by comparing the 3H/14C ratio in the skulls with that in the injected solution, which appeared to be a better method than comparing the recovery of each compound.
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In the intact kidney, renal proximal tubule cells accumulate p-aminohippurate (PAH) via a basolateral, probenecid- and sodium-sensitive transport system. Primary cultures of rabbit proximal tubule cells retain sodium-glucose co-transport in culture, but little is known about PAH transport in this system. Purified proximal tubule cells from a rabbit were grown in culture and assessed for PAH and alpha-methyl-D-glucoside uptake capacities as well as proximal tubule marker enzyme activities. Control PAH uptake on collagen-coated filters (20 +/- 3 pmol/mg protein.min; n = 8) was not significantly different from uptake in the presence of 1 mM probenecid (19 +/- 4 pmol/mg protein.min; n = 8). Uptake from the basal side of the cell was 3.9 +/- 0.7 times greater than that from the apical side. In multi-well plate studies, the uptake was significantly reduced by removing sodium from the medium and stimulated by coating the wells with collagen. Glutarate (10 mM) had no effect on the uptake of PAH. Other differentiated proximal tubule characteristics were retained in culture, including the ability to form domes and to transport glucose by a phlorizin-sensitive system. Phlorizin-sensitive 1 mM alpha-methyl-D-glucoside uptake was 134 +/- 42 pmol/mg protein.min (n = 7; P less than 0.02). The proximal tubule marker enzymes alkaline phosphatase and gamma-glutamyltranspeptidase, increased in activity in the cultures after confluence. It was concluded that whereas some differentiated properties were retained during primary culture of rabbit proximal tubule cells, the PAH transport system was selectively lost or modified from that present in the intact kidney.
Effect of the prostaglandin synthesis inhibitor, indomethacin (indo) were studied on renal PAH transport (a) in renal cortical slices in vitro and (b) in anaesthetized dogs with various levels of plasma PAH concentrations (b1:PPAH less than 3 mg/dl and b2:PPAH V greater than 20 mg/dl] in vivo. It was found that: (a) indomethacin in concentrations of 0.4 and 4.0 micrograms/ml failed to influence PAH accumulation (S/M) and K or Na contents in renal cortical slices, whereas in a concentration of 40 micrograms/ml it potently decreased PAH accumulation (S/Mcontrol: 4.62 +/- 0.76, S/Mindo: 2.38 +/- 0.41; p less than 0.001). The oxygen uptake by tissue slices remained unaltered in the presence of indomethacin. (b1) Indomethacin in a dose of 4 mg/kg produced a pronounced antidiuresis and antinatriuresis with no change in GFR. PAH secretion was slightly reduced (TPAH control: 3.97 +/- 1.21; TPAH indo: 3.21 +/- 1.55 mg/min/100 g; p less than 0.01). (b2) Indomethacin appreciably decreased the secretory maximum of tubules (TmPAH control: 10.0 +/- 4.39; TmPAH indo: 4.95 +/-3.83 mg/min/100 g; p less than 0.001). Based on these results it is concluded that indomethacin, even when applied in the usual concentration, might partially block certain enzymes in the kidney.
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