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

Abstract

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 2 h. 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.

Proximal Tubulopathies Associated With Monoclonal Light Chains: The Spectrum of Clinicopathologic Manifestations and Molecular Pathogenesis

“…In the 1960s and 70s, Costanza and Smoller, 16 as well as Maldonado et al, 17 suggested that proximal tubular damage was an important pathologic finding in some patients with myeloma and renal dysfunction. About the same time, experimental studies 18 performed by using isolated perfused rat kidneys showed that light chains purified from the urine of patients with Bence Jones proteinuria did not alter proximal tubular function; morphologic alterations in proximal tubules were stated to be absent, creating doubts about the ability of light chains to induce proximal tubular damage. Furthermore, in the mid 1970s, Clyne et al 19 demonstrated intracytoplasmic inclusions in proximal tubular cells, but when they injected Bence Jones proteins intraperitoneally, glomerular filtration rate remained normal, further supporting the prevalent belief of the time.…”

Multiple Myeloma

“…The diagnosis of cast nephropathy is based on the demonstration of tubular casts in the distal nephron that are composed of Ig light chains, and the light chain in the cast is the same as that in the serum and urine (31); immunofluorescence microscopy demonstrates staining restricted to one or the other light chain (Figure 1). The casts contain either Ig light chain, Ig, and other serum proteins (31)(32)(33)(34)(35)(36), including Tamm-Horsfall glycoprotein. In hematoxylin-and eosin-stained sections, the casts are intensely eosinophilic, and they seem "brittle" because they are lamellated and fractured frequently (Figure 2).…”

Renal Handling of β-Trace Protein: Interpreting the Evidence

“…The proximal tubule is known to endocytose a number of low-molecular-weight proteins, 3-5 and the molecular size of BTP is similar to light chains (w25,000 Da) that are filtered and metabolized by the kidney. 6 We agree that further investigations are needed to define renal handling of BTP; for example, determining whether proximal tubular cells uptake BTP in vitro 7,8 and additional measurements of BTP clearance in vivo using methods that do not rely on radioactive labels. …”