Nephrotoxic Potential of Bence Jones Proteins

Alan Solomon, Deborah T. Weiss, Anthony A. Kattine

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

Background. The renal manifestations of diseases associated with the production of monoclonal light chains—myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL—result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. Methods. Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. Results. Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 μmol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 μmol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. Conclusions. Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain—associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains. (N Engl J Med 1991; 324:1845–51.)

Original languageEnglish (US)
Pages (from-to)1845-1851
Number of pages7
JournalNew England Journal of Medicine
Volume324
Issue number26
DOIs
StatePublished - Jun 27 1991

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Bence Jones Protein
Kidney
Light
Amyloidosis
Proteins
Basement Membrane
Creatinine
Injections
Serum
Multiple Myeloma
Amyloid
Immune Sera
Electron Microscopy
Theoretical Models

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Nephrotoxic Potential of Bence Jones Proteins. / Solomon, Alan; Weiss, Deborah T.; Kattine, Anthony A.

In: New England Journal of Medicine, Vol. 324, No. 26, 27.06.1991, p. 1845-1851.

Research output: Contribution to journalArticle

Solomon, Alan ; Weiss, Deborah T. ; Kattine, Anthony A. / Nephrotoxic Potential of Bence Jones Proteins. In: New England Journal of Medicine. 1991 ; Vol. 324, No. 26. pp. 1845-1851.
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abstract = "Background. The renal manifestations of diseases associated with the production of monoclonal light chains—myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL—result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. Methods. Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. Results. Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 μmol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 μmol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. Conclusions. Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain—associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains. (N Engl J Med 1991; 324:1845–51.)",
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AB - Background. The renal manifestations of diseases associated with the production of monoclonal light chains—myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL—result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. Methods. Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. Results. Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 μmol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 μmol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. Conclusions. Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain—associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains. (N Engl J Med 1991; 324:1845–51.)

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