Characteristics of Renal Handling of Human Light Chain by the Perfused Rat Kidney

1978 ◽  
Vol 54 (2) ◽  
pp. 3P-3P
Author(s):  
J. F. Falconer Smith ◽  
R. I. van Hegan ◽  
M. P. Esnouf ◽  
B. D. Ross
1979 ◽  
Vol 57 (1) ◽  
pp. 113-120 ◽  
Author(s):  
J. F. Falconer Smith ◽  
R. I. Van Hegan ◽  
M. P. Esnouf ◽  
B. D. Ross

1. The renal handling of purified human immunoglobulin light chain has been studied with an isolated perfused rat kidney preparation. 2. Human immunoglobulin light chain was freely filtered and largely reabsorbed. Fractional reabsorption was characteristic for each of four light chains and varied between 56% and 86%. No renal tubular maximum for human light chain was obtained. 3. Light chains at concentrations up to 10 times those seen in human myeloma were without effect on glomerular filtration rate or sodium and potassium reabsorption in experiments lasting up to 2h. 4. Filtered and reabsorbed light chain returned ultimately to the perfusion medium, indicating a unique property of the tubular handling of this protein. None of the inhibitors tested (ouabain, frusemide, acetazolamide, probenicid) influenced light chain reabsorption. 5. The results are taken to indicate that light chain reaches the site of the transport enzyme, Na+, K+−dependent ATPase, at concentrations which vary with the nature of the light chain. This may provide a mechanism for renal damage in patients with myeloma, after prolonged exposure.


1990 ◽  
Vol 183 (6) ◽  
pp. 2077
Author(s):  
P.G.F. Cox ◽  
M.M. Moons ◽  
F.G.M. Russel ◽  
C.A.M. van Ginneken

1986 ◽  
Vol 70 (6) ◽  
pp. 595-599 ◽  
Author(s):  
P. J. Ratcliffe ◽  
M. P. Esnouf ◽  
J. G. G. Ledingham

1. The renal handling of myoglobin has been studied in the isolated perfused rat kidney. 2. Myoglobin was freely filtered. Reabsorption by the renal tubules showed saturation kinetics with a relatively low maximum rate of reabsorption (Tmax) of 27-30 μg min−1 g−1 wet wt. at a perfusate concentration of 70-80 μg/ml. Myoglobin reabsorption is therefore much less than that reported for immunoglobulin light chain or lysozyme in this model. 3. Large increases in sodium and water excretion produced by omission of oncotic agent from the perfusate did not alter the kinetics of myoglobin reabsorption. 4. The use of bovine serum albumin as oncotic agent in the perfusate prevented the tubular reabsorption of myoglobin. Small amounts of albumin are filtered by the isolated perfused kidney and it is postulated that this albumin interferes with tubular reabsorption of myoglobin.


1994 ◽  
Vol 83 (5) ◽  
pp. 723-726 ◽  
Author(s):  
Tetsuya Aiba ◽  
Yoshie Itoga ◽  
Hiromasa Shimizu ◽  
Yusuke Tanigawara ◽  
Ryohei Hori

Pharmacology ◽  
1991 ◽  
Vol 42 (5) ◽  
pp. 287-296 ◽  
Author(s):  
Peter G.F. Cox ◽  
Miek M. Moons ◽  
Frans G.M. Russel ◽  
Cees A.M. van Ginneken

2014 ◽  
Vol 58 (10) ◽  
pp. 5650-5657 ◽  
Author(s):  
František Trejtnar ◽  
Jana Mandíková ◽  
Jana Kočíncová ◽  
Marie Volková

ABSTRACTAmphotericin B (AmB) is excreted via the renal excretion route. This excretion process may result in nephrotoxicity. However, relevant information on the precise renal excretion mechanisms is not available. The aim of the study was to analyze the possible interaction of AmB or its prodrug AmB deoxycholate (AmB-DOC) with the typical renal organic anion transporters (OATs) and organic cation transporters (OCTs), using cellular and organ models. The relevant transport systems were then investigated in terms of the drug-drug interactions of AmB-DOC with antivirals that might potentially be used concomitantly. To analyze the renal excretion mechanisms of [3H]AmB, perfused rat kidney was employed. HeLa and MDCK II cells transiently transfected with human OAT1 (hOAT1) or hOCT2 were used as the cellular models. A significant tubular secretion of AmB was demonstrated in the perfused rat kidney. The cellular studies performed confirmed the active transport of AmB into cells. AmB did not interact with hOAT1 but strongly inhibited hOCT2. In contrast, AmB-DOC inhibited both hOAT1 and hOCT2. However, [3H]AmB cellular uptake by hOAT1 and hOCT2 was not found. AmB-DOC interacted significantly with adefovir, tenofovir, and cidofovir in hOAT1-transfected cells at supratherapeutic concentrations. In conclusion, the significant potency of AmB and AmB-DOC for inhibiting the transporters was demonstrated in this study. The secretion of AmB in the renal tubules is likely not related to the transporters here, since the drug was not proven to be a substrate for them. Drug-drug interactions of AmB and the antivirals used in this study on the investigated transporters are not probable.


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