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Nephrotoxic potential of Bence Jones proteins.
N Engl J Med. 1991 Jun 27; 324(26):1845-51.NEJM

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 mumol 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 mumol 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.

Authors+Show Affiliations

Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1904132

Citation

Solomon, A, et al. "Nephrotoxic Potential of Bence Jones Proteins." The New England Journal of Medicine, vol. 324, no. 26, 1991, pp. 1845-51.
Solomon A, Weiss DT, Kattine AA. Nephrotoxic potential of Bence Jones proteins. N Engl J Med. 1991;324(26):1845-51.
Solomon, A., Weiss, D. T., & Kattine, A. A. (1991). Nephrotoxic potential of Bence Jones proteins. The New England Journal of Medicine, 324(26), 1845-51.
Solomon A, Weiss DT, Kattine AA. Nephrotoxic Potential of Bence Jones Proteins. N Engl J Med. 1991 Jun 27;324(26):1845-51. PubMed PMID: 1904132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nephrotoxic potential of Bence Jones proteins. AU - Solomon,A, AU - Weiss,D T, AU - Kattine,A A, PY - 1991/6/27/pubmed PY - 1991/6/27/medline PY - 1991/6/27/entrez SP - 1845 EP - 51 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 324 IS - 26 N2 - 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 mumol 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 mumol 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. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/1904132/Nephrotoxic_potential_of_Bence_Jones_proteins_ L2 - http://www.nejm.org/doi/full/10.1056/NEJM199106273242603?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -