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Diagnosis: Light Chain Proximal Tubulopathy

The most common paraprotein-related diseases of the kidney are amyloidosis, light chain deposition disease and light chain cast nephropathy. Less common forms of paraproteinemic disease in multiple myeloma include light chain proximal tubulopathy, cryoglobulinemic glomerulonephritis (GN), proliferative GN with monoclonal immunoglobulin deposits, immunotactoid glomerulopathy, fibrillary GN, and crystal storing histiocytosis. Rarely, monoclonal immunoglobulin may also cause C3 glomerulopathy or atypical hemolytic uremic syndrome by interfering with the regulation of the alternative pathway of complement.

In our case a bone marrow biopsy confirmed the diagnosis of multiple myeloma.

There is a wide spectrum of monoclonal gammopathies, extending from the premalignant process called monoclonal gammopathy of undetermined significance (MGUS) to overt malignancy such as multiple myeloma and Waldenström macroglobulinemia. Patients with monoclonal gammopathies may develop symptoms not just because of malignant transformation, but also because of idiosyncratic properties of the secreted monoclonal (M) protein. Thus, disorders such as AL amyloidosis, cryoglobulinemia, and cold-agglutinin disease may occur without the need for malignant transformation, primarily because of the unique disease-producing properties of the individual M protein (Sethi S, et al. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25(2):127-37. [PubMed link]).

The monoclonal gammopathy-associated renal diseases are distinct in their pathogenesis, kidney biopsy findings, clinical presentation, progression, prognosis, and treatment. The term "monoclonal gammopathy of renal significance" helps highlight patients who have renal disease secondary to monoclonal immunoglobulin secreted by a premalignant or malignant clone, but is not a disease or diagnosis in itself (Sethi S, et al. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25(2):127-37. [PubMed link]).

In light chain proximal tubulopathy there is usually positivity only for a light chain, interestingly in our case there was also positivity for IgG, in fact, in the patient's serum there were high levels of IgG kappa. But we believe that the large amount of the light chain component in the tubules is the pathogenic factor. We did not find in the literature "light and heavy chains tubulopathy".

See the chapter: Amyloidosis, Multiple Myeloma... of our Tutorial.

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References

  • Stokes MB, Valeri AM, Herlitz L, Khan AM, Siegel DS, Markowitz GS, D'Agati VD. Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era. J Am Soc Nephrol. 2016;27(5):1555-65. [PubMed link]
  • Sethi S, Fervenza FC, Rajkumar SV. Spectrum of manifestations of monoclonal gammopathy-associated renal lesions. Curr Opin Nephrol Hypertens. 2016;25(2):127-37. [PubMed link]
  • Al-Hussain T, Hussein MH, Al Mana H, Akhtar M. Renal involvement in monoclonal gammopathy. Adv Anat Pathol. 2015;22(2):121-34. [PubMed link]
  • Sanders PW. Mechanisms of light chain injury along the tubular nephron. J Am Soc Nephrol. 2012;23(11):1777-81. [PubMed link]
  • Christopher P. Larsen, G. Scott Borrelli, and Patrick D. Walker. Amyloid proximal tubulopathy: a novel form of light chain proximal tubulopathy. Clinical Kidney Journal 2012;5:130-2. [Abstract]

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