Article

Paraproteinemic Renal Diseases that Involve the Tubulo-Interstitium

Department of Pathology, St. Louis University, St. Louis, Mo., USA.
Contributions to nephrology (Impact Factor: 1.8). 02/2007; 153:105-15. DOI: 10.1159/000096763
Source: PubMed

ABSTRACT

The renal response to deposition of monoclonal light chains represents a spectrum of pathologic changes that can be divided into glomerular or tubulo-interstitial processes. Involvement of the tubulo-interstitium can include activation of the proximal tubule, proximal tubule injury/cell death, and cast nephropathy. In these diseases, the culprit is not the intact immunoglobulin protein but instead the immunoglobulin light chain. Recent noninvasive tests, including immunofixation electrophoresis or quantification of serum free light chains, have increased the sensitivity for detection of an abnormality in circulating free light chains and are invaluable ancillary tools, but short of renal biopsy, the diagnosis of these diseases can prove challenging. A description of the pathobiology and overview of the approach to management of these light chain-mediated renal lesions is provided.

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    • "As a consequence, large amounts of FLCs reach the distal tubule lumen where they interact specifically with Tamm-Horsfall proteins (THPs; also known as uromodulin), generating myeloma casts. Cast formation in the distal tubule can block glomerular flow and cause proximal tubular atrophy [19], also contributing to interstitial fibrosis [20]. Simultaneously, the massive reabsorption of monoclonal FLCs within the proximal tubules induces proximal tubule cells apoptosis and DNA degradation, resulting in critical morphologic changes, such as epithelial-to-mesenchymal transition (EMT) or necrosis [21]. "
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    ABSTRACT: In plasma cell dyscrasias, involvement of the distal tubules is frequent and well characterized. In contrast, proximal tubules have only rarely been reported to show diagnostic pathology such as intracytoplasmic crystals. To look for additional morphologic features that might be helpful in the diagnosis of proximal tubulopathy associated with an underlying plasma cell dyscrasia. We examined patients presenting with nonspecific renal symptoms who were found to have light chain restriction limited to proximal tubular epithelium by immunofluorescence. We correlated these results with light microscopy, electron microscopy, and the clinical findings. By immunofluorescence, 5 patients had light chain restriction in proximal tubular epithelium. By light microscopy, only 1 patient had focal rhomboid crystals in the proximal tubular epithelium; all other biopsies failed to show any discernible pathology within the proximal tubules or elsewhere in the kidney. By electron microscopy, proximal tubules from 2 patients showed crystals with a latticelike structure, whereas the remaining 3 patients had only prominent phagolysosomes. However, by immunoelectron microscopy, the lysosomal content showed light chain restriction (in 2 cases studied). Post-kidney biopsy, all patients were diagnosed with multiple myeloma or plasma cell dyscrasia. One patient developed renal failure and had recurrence of crystals in the allograft. Light chain proximal tubulopathy may be associated with the presence of crystals or with the presence of phagolysosomes with light chain restriction as the sole abnormality. Both kappa and lambda light chains may be involved. The prognosis is variable and the pathology may recur in transplants.
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