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

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.

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

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.


1988 ◽  
Vol 74 (6) ◽  
pp. 639-644 ◽  
Author(s):  
Christine Baylis ◽  
James Falconer-Smith ◽  
Brian Ross

1. To examine the effect of charge and molecular size on the renal handling of immunoglobulin light chain, three different human light chains were purified, iodinated and characterized with regard to molecular weight and isoelectric point. The molecular weights were similar, whereas the isoelectric points ranged from markedly cationic to markedly anionic. 2. Renal handling of the light chains was determined in vivo in the Munich–Wistar rat and in vitro in the isolated perfused rat kidney. 3. Significant restriction to the transglomerular passage of all three light chains was evident in the intact kidney, with the most anionic light chain being restricted most while the cationic light chain was restricted least. The charge dependence of filtration of these naturally occurring proteins was, however, much less pronounced than has previously been reported for the synthetic dextrans. 4. Tubular reabsorption of the three light chains was quite variable in the intact kidney and did not appear to be related to molecular charge. In the isolated perfused kidney, once account had been taken of the abnormally high rate of filtration of these proteins, the reabsorption of the three light chains was strikingly similar to that seen in vivo. 5. With these three purified human light chains no marked influence of charge (pI) has been demonstrated in vivo or in vitro, for glomerular restriction or renal tubular reabsorption. Some other properties of human myeloma light chains may determine their renal handling and nephrotoxicity.


Toxicon ◽  
2019 ◽  
Vol 165 ◽  
pp. 40-46
Author(s):  
Mauren Villalta ◽  
Tiago Lima Sampaio ◽  
Ramon Róseo Paula Pessoa Bezerra de Menezes ◽  
Dânya Bandeira Lima ◽  
Antônio Rafael Coelho Jorge ◽  
...  

1985 ◽  
Vol 249 (5) ◽  
pp. E494-E497 ◽  
Author(s):  
R. M. Rosa ◽  
P. Silva ◽  
J. S. Stoff ◽  
F. H. Epstein

Vasoactive intestinal peptide, a polypeptide neurotransmitter, stimulates salt secretion by the mammalian intestine and the rectal gland of the dogfish shark. Because of the recent identification of vasoactive intestinal peptide in renal nerves, the present study was undertaken to investigate its effects on the isolated perfused rat kidney. The addition of vasoactive intestinal peptide to the recirculating perfusate produced a significant increase in urine volume, fractional excretion of sodium, chloride, and potassium, as well as osmolar clearance when compared with control kidneys. These changes associated with addition of vasoactive intestinal peptide occurred without any significant changes in perfusion flow, renal vascular resistance, or inulin clearance. These experiments strongly suggest an action of vasoactive intestinal peptide on renal tubular reabsorption.


1989 ◽  
Vol 256 (5) ◽  
pp. F901-F908
Author(s):  
K. A. Roby ◽  
S. Segal

Renal tubular reabsorption of cystine and lysine were studied in the isolated perfused rat kidney to bridge the gap between in vivo clearance studies, and in vitro transport studies of tubule fragments, cells, and brush-border membranes. Lysine was reabsorped by a saturable transport system shared by the dibasics. Cystine was also reabsorbed by a saturable transport system, which was shared in part by the dibasics (maximum inhibition 30%). The lysine threshold (Fmin) was 0.9 mumol.min-1.g-1, with a tubular maximum (TM) of 2.4 mumol.min-1.g-1. The cystine Fmin was 0.06 mumol.min-1.g-1; the TM could not be estimated because it was above the limit of cystine solubility. There was no evidence of cystine ,secretion.- The gamma-glutamyltransferase inhibitor, AT-125, decreased cystine excretion, but only in the presence of glutathione, glycine, glutamate, and the diabasic amino acids. This suggests that cystine from glutathione degradation at the brush border may contribute to urinary cystine (an explanation of the phenomenon of cystine secretion), but only under certain conditions.


Blood ◽  
2014 ◽  
Vol 123 (22) ◽  
pp. 3440-3451 ◽  
Author(s):  
Ping Zhou ◽  
Xun Ma ◽  
Lakshmanan Iyer ◽  
Chakra Chaulagain ◽  
Raymond L. Comenzo

Key PointsImmunoglobulin light-chain and antibody production by plasma cells is significantly reduced by siRNA for the light-chain constant region. In plasma cells making intact antibodies, knockdown of light chains can cause terminal ER stress because of unpaired heavy chains.


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