Light chain proximal tubulopathy with cast nephropathy in monoclonal gammopathy of renal significance

2020 ◽  
Vol 13 (6) ◽  
pp. e234361
Author(s):  
Rebaika Chopra ◽  
Rosalba Santana de Roberts ◽  
Ibrahim Batal ◽  
Sachin Batra ◽  
Belinda Jim
Keyword(s):  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Fanconi Syndrome ◽  
Cell Damage ◽  
Biochemical Properties ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
Cast Nephropathy ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy

Kidney tubular disorders due to monoclonal immunoglobulin light chains are common manifestations of B-cell neoplasm. Cast nephropathy (CN) is the most frequent type of these disorders and may present with acute kidney injury (AKI) due to the presence of excess light chains in the distal tubules. Light chain proximal tubulopathy (LCPT) is an uncommon form of renal disease and may present as Fanconi syndrome due to proximal tubular cell damage by intracellular deposition of light chains. The concomitant disorder of both CN and LCPT is rare given the inherent differences in the biochemical properties of the immunoglobulin light chains of each disorder. We report a 64-year-old man who presented with AKI and Fanconi syndrome who was discovered to have both CN and LCPT due to the underlying disorder of monoclonal gammopathy of renal significance and who has responded favourably with conventional chemotherapy. We also review the existing literature on this interesting subject.

Monoclonal immunoglobulin–mediated kidney disease: What is beyond amyloidosis in real practice?

2019 ◽  
Vol 3 (3) ◽  
pp. 105-112 ◽  
Author(s):  
Elena V Zakharova ◽  
Tatyana A Makarova ◽  
Ekaterina S Stolyarevich ◽  
Olga A Vorobyeva
Keyword(s):  
Kidney Disease ◽  
B Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Monoclonal Immunoglobulin ◽  
B Cell Malignancies ◽  
Cast Nephropathy ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy

Background:Monoclonal immunoglobulin–mediated kidney disease with various patterns of damage may occur in patients with B-cell malignancies and non-malignant monoclonal gammopathies, and the latter are actually merged under the umbrella of monoclonal gammopathy of renal significance. Amyloidosis is the most well-known monoclonal immunoglobulin–related kidney damage. We focused on the rarer conditions and aimed to evaluate the non-amyloid spectrum of monoclonal immunoglobulin–mediated patterns of renal damage in real clinical practice.Methods:A single-center non-interventional retrospective study included 45 patients with pathology-proven non-amyloid monoclonal immunoglobulin–mediated kidney disease, followed during 2002–2018. Disease duration, proteinuria, serum creatinine, need for dialysis at the time of kidney biopsy, clinical diagnosis, and kidney pathology findings were analyzed.Results:No significant differences in the median age, disease duration at the time of biopsy, or main clinical presentation of kidney disease were found between patients with monoclonal gammopathy of renal significance and patients with B-cell malignancies. Pathology patterns like proliferative glomerulonephritis with monoclonal immunoglobulin deposits, membranous nephropathy, C3 glomerulopathy, cryoglobulinemic glomerulonephritis, and combinations of light chain proximal tubulopathy with monoclonal immunoglobulin deposition disease, and of C3 glomerulopathy with light chain proximal tubulopathy were found in monoclonal gammopathy of renal significance setting only. In contrast, light chain proximal tubulopathy alone, anti-glomerular basement glomerulonephritis, and combinations of cast nephropathy with light chain proximal tubulopathy, and cast nephropathy with monoclonal immunoglobulin deposition disease were associated with multiple myeloma only. Monoclonal immunoglobulin deposition disease, intracapillary monoclonal immunoglobulin M deposits, and cast nephropathy alone were seen in both settings.Conclusion:The presence of monoclonal gammopathy in patients with proteinuria and/or impaired kidney function demands kidney biopsy. Neither duration of kidney disease nor its clinical presentation allows differentiating malignant and non-malignant causes of monoclonal immunoglobulin–mediated renal damage. Several pathology patterns, even cast nephropathy, can be found both in cases of monoclonal gammopathy of renal significance and in cases of B-cell malignancies. Dual patterns of damage, including combinations of organized and non-organized deposits, or organized deposits with monoclonal immunoglobulin–induced damage without monoclonal immunoglobulin deposition, constitute up to 9%, mostly in multiple myeloma cases.

Trifecta of light chain cast nephropathy, monoclonal plasma cell infiltrates, and light chain proximal tubulopathy

2017 ◽  
Vol 92 (6) ◽  
pp. 1559 ◽  
Author(s):  
Abhilash Koratala ◽  
A. Ahsan Ejaz ◽  
Wesley M. Hiser ◽  
William L. Clapp
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Cast Nephropathy ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy

Rare presentation of kappa light chain proximal tubulopathy with fibrillar aggregates

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S154-S154
Author(s):  
A M Alkashash ◽  
C L Phillips
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Primary Amyloidosis ◽  
Renal Tubules ◽  
Kappa Light Chain ◽  
Rare Presentation ◽  
Cast Nephropathy ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy

Abstract Introduction/Objective Patients with dysproteinemias may show a spectrum of renal alterations due to organized deposits of excess immunoglobulins, including primary amyloidosis, myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, and light chain proximal tubulopathy (LCPT). Among the least common is LCPT, which shows ultrastructural cytoplasmic light chain inclusions with crystalline morphology or rarely fibrillar aggregates. We present the case of a patient with LCPT with fibrillar aggregates that is the only such case registered in our large academic surgical pathology electronic database. Our aim is to increase understanding and recognition of this rare variant. Methods/Case Report A 73-year-old man presented with 540 mg/day proteinuria, serum creatinine 5.73 mg/dL, platelets 178,000/cc, and 20% plasma cells in his bone marrow biopsy specimen. Kidney needle biopsy cores examined by light, fluorescent and transmission electron microscopy (EM) showed kappa light chain cast nephropathy and kappa LCPT with fibrillary aggregates, the latter requiring unmasking of kappa epitopes using pronase-treated paraffin sections. Congo red stain was negative. By EM, proximal tubules contained intracellular bundles of tightly aggregated fibrils with mean fibril diameter of 7.7 +/- 1.6 nm. Individual bundles were variably shaped as round, oval, spicular or irregular blobs. Fibrils were not seen in glomeruli. Results (if a Case Study enter NA) NA Conclusion This rare presentation of LCPT with fibrillar aggregates reinforces the utility of renal biopsy diagnosis that includes careful ultrastructural examination of renal tubules. In the absence of EM, the unique fibrillar organization of these cytoplasmic light chain aggregates would otherwise go unrecognized.

scholarly journals Crystalline deposits in the cornea and various areas of the kidney as symptoms of an underlying monoclonal gammopathy: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
C. Lindemann ◽  
P. Enders ◽  
P. T. Brinkkoetter ◽  
L. A. Völker
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Wide Spectrum ◽  
Diagnostic Testing ◽  
Percutaneous Biopsy ◽  
Light Chains ◽  
Crystalline Deposits ◽  
Light Chain Proximal Tubulopathy ◽  
Monoclonal Proteins

Abstract Background Plasma cell dyscrasias (PCD) are characterized by an abnormal production of intact monoclonal immunoglobulins or parts such as heavy or light chains. In most cases, the monoclonal protein (also termed paraprotein) is produced by a clonal plasma cell population. The production of monoclonal proteins can result in deposits of various types and localization depending on the type, amount, and electrochemical properties of the paraprotein. One histopathologic presentation, albeit rare, are crystalline deposits. They can form in various organs and hence cause a wide spectrum of symptoms. Case presentation A 49-year-old man presented to the emergency department with eyestrain and foreign body sensation after overhead drilling. Examination of the eyes revealed crystalline deposits in the cornea of both eyes. After additional diagnostic testing, deposits were attributed to free light chains. Monoclonal gammopathy of undetermined significance (MGUS) was diagnosed according to serum electrophoresis and immunofixation. Four years later, new onset of proteinuria was detected. A percutaneous biopsy of the kidney showed severe light chain podocytopathy with secondary focal segmental glomerulosclerosis (FSGS) and light chain proximal tubulopathy (LCPT). In these lesions, crystalline deposits identical to the corneal deposits were found in ultrastructural and immunofluorescent analysis. The patient was diagnosed with monoclonal gammopathy of renal significance (MGRS), and a plasma cell directed therapy was initiated. Conclusions PCD can present with a wide array of symptoms and are notoriously difficult to diagnose. Extrarenal manifestations such as crystalline deposits in the cornea are one possible manifestation. The case presented herein emphasizes the notion that extrarenal paraprotein deposits warrant a thorough search for the underlying clonal disease.

scholarly journals Light chain proximal tubulopathy with cast nephropathy in a case of multiple myeloma

2015 ◽  
Vol 25 (2) ◽  
pp. 119 ◽  
Author(s):  
KK Gowda ◽  
K Joshi ◽  
R Nada ◽  
R Ramachandran ◽  
M Sachdeva
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Cast Nephropathy ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy

scholarly journals Light Chain Proximal Tubulopathy: Expanding the Pathologic Spectrum with and without Deposition of Crystalline Inclusions

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Shree G. Sharma ◽  
Steven M. Bonsib ◽  
Didier Portilla ◽  
Ashutosh Shukla ◽  
Adam B. Woodruff ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Multiple Myeloma ◽  
Renal Disease ◽  
Physicochemical Properties ◽  
Light Chain ◽  
Proximal Tubules ◽  
Light Chains ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy ◽  
Crystal Accumulation

Light chain proximal tubulopathy (LCPT) is an uncommon form of renal disease associated with dysproteinemias. It is characterized by intracytoplasmic deposition of crystallized mostly kappa monoclonal light chains in proximal tubules (PTs). Crystals are located within lysosomes by electron microscopy (EM). Rare lambda LCPT cases without crystals by EM were described. Retrospectively, we reviewed clinical, light microscopic (LM), immunofluorescence (IF), and EM findings in 9 cases) (8 males, 1 female; mean age 57 years (38–81)) with multiple myeloma. LM showed abundant cytoplasmic droplets in PT cells in all cases. Droplets were also present in the podocytes, endothelial and parietal cells in one case. IF revealed staining of crystals with kappa in 3 and lambda in 6. EM showed electron dense rectangular, rhomboid, or needle shaped crystals in PT cells in 3 cases (33%), one of which had crystals in podocytes and interstitial cells. Six lambda LCPT cases showed no crystals by EM (67%). This may reflect differences in the physicochemical properties of light chains. The mechanisms of crystal accumulation in these cells and the significance of this finding are unknown.

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