Renal complications in multiple myeloma: Pathophysiology and some aspects of clinical management

Martínez‐Maldonado, Manuel; Yium, Jackson; Suki, Wadi N.; Eknoyan, Garabed

doi:10.1016/0021-9681(71)90076-2

Cited by 67 publications

(11 citation statements)

References 49 publications

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“…In all studied cases of Fanconi syndrome, the light chain was of the x-type [13,24], Similarly, peritubular deposits of light chains reported by several authors in myeloma were always of the x-type [14]. The type of light chain associ ated with myeloma proteins does not seem to be distributed at random [20].…”

Section: Qualitative Aspectsmentioning

confidence: 99%

“…This process may be either pro gressive, or acute and massive, the mechanism being basically the same. It may be precipitated by several known aggravating factors [2,7,14], such as dehydration, which decreases urinary flow and increases concentration; hypercalcemia; or, to a lesser extent, hyper uricemia. Finally, radiologic contrast media might favor precipitation of light chains and of Tamm-Horsfall mucoprotein [10].…”

Section: Pathogenetic Role O F Free Light Chainsmentioning

confidence: 99%

“…Our purpose is not to review the clinicopathological data concerning the occurrence of renal disease during the course of dysproteinemias. Many recent general reviews have dealt with this topic [4,8,14,20,30], We shall only attempt to summa rize current pathogenetic data.…”

mentioning

confidence: 99%

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Pathogenesis of Renal Disease in Monoclonal Gammopathies: Current Concepts

Beaufils¹,

Morel-Marogér²

1978

Nephron

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Section: Qualitative Aspectsmentioning

confidence: 99%

Section: Pathogenetic Role O F Free Light Chainsmentioning

confidence: 99%

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Pathogenesis of Renal Disease in Monoclonal Gammopathies: Current Concepts

Beaufils¹,

Morel-Marogér²

1978

Nephron

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“…Since Bartels et al reported the first case of ARF after intravenous urography in a patient with monoclonal disease in 1954 [10], other similar cases were published in the literature in the years to follow between 1950 and 1980 [14][15][16][17][18][19][20][21][22][23][24][25] with consequent important contraindications to the use of iodine-based contrast agents with high osmolarity which were routinely used in that period.…”

Section: Discussionmentioning

confidence: 96%

Effect on renal function of an iso-osmolar contrast agent in patients with monoclonal gammopathies

et al. 2010

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“…We posit that the tissue deposition of light chains is governed by the concepts of mass action that underlie all molecular interactions. In addition, host-related factors, such as dehydration, affect cast formation in the kidney (20)(21)(22). Since this process results in an increased protein concentration-a condition we find to increase aggregate formation exponentially-this phenomenon could account for the renal tubular deposition of an apparently nontoxic Bence Jones protein (23).…”

Section: Methodsmentioning

confidence: 99%

Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition.

Myatt

Westholm

Weiss

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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The deposition of certain Bence Jones proteins as tubular casts, basement membrane precipitates, or amyloid fibrils results in the human light-chain-associated renal and systemic dis -myeloma (cast) nephropathy, light-chain deposition disease, and immunocyte-derived (primary or AL) amyloidosis. To determine if light-chain nephrotoxicity or amyloidogenicity is related to the propensity of these components to form high molecular weight aggregates under physiological conditions, we used a size-exclusion chromatographic system to study 40 different Bence Jones proteins. Each sample was tested over a wide range of protein concentration in three different buffers varying in pH, osmolality, and the presence or absence oflow concentrations ofurea. Thirty-three of the 35 proteins found clinically and/or experimentally to form in vivo pathologic light-chain deposits were shown to undergo high-order self-association and form hh molecular weight aggregates. In contrast, of five nonpathologic proteins, one showed polymerization under the chromatographic conditions used. The correlation between the in vitro results achieved by size-exclusion chromatography and that found in vivo provides (i) a rapid dlagnostic method to identify potential nephrotoxic or amyloidogenic Bence Jones proteins and (ii) an experimental means to gain new insight into the physicochemical basis of light-chain aggregtion and the treatment of those invariably fatal disorders associated with pathologic lightchain deposition.The human light-chain-related renal and systemic diseasesmyeloma (cast) nephropathy, light-chain deposition disease, and immunocyte-derived (primary or AL) amyloidosisresult from the pathologic deposition of monoclonal light chains (i.e., Bence Jones proteins) in the form of casts, basement membrane precipitates, or fibrils, respectively (1). These light-chain deposits ultimately result in the impairment ofrenal and other organ function and account for much ofthe morbidity and mortality found in patients with these disorders. The fact that pathologic light-chain deposits are not an invariant accompaniment of clinical or experimental (1) Bence Jones proteinuria and are not necessarily directly related to the amount of monoclonal light chain synthesized or excreted implies that certain light chains are inherently nephrotoxic or amyloidogenic.Several in vitro and in vivo models have been devised that provide an experimental means to assess the pathologic potential of Bence Jones proteins (2-5). For example, in one model we demonstrated that the injection into mice ofcertain Bence Jones proteins resulted in the deposition in the mouse kidney of the human proteins in the form of tubular casts, basement membrane precipitates, crystals, or amyloid fibrils (6). Through studies involving >40 different Bence Jones proteins, we found that the renal lesions induced experimentally were comparable to those of patients from whom the proteins were derived and that the experimental mouse model was capable of differentiating "nephrotoxic" from "...

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Renal complications in multiple myeloma: Pathophysiology and some aspects of clinical management

Cited by 67 publications

References 49 publications

Pathogenesis of Renal Disease in Monoclonal Gammopathies: Current Concepts

Pathogenesis of Renal Disease in Monoclonal Gammopathies: Current Concepts

Effect on renal function of an iso-osmolar contrast agent in patients with monoclonal gammopathies

Pathogenic potential of human monoclonal immunoglobulin light chains: relationship of in vitro aggregation to in vivo organ deposition.

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