Amyloid cast nephropathy: A rare presentation of multiple myeloma–associated light chain amyloidosis

Introduction: Monoclonal immunoglobulins can cause a variety of histologic patterns of kidney injury, depending on the physicochemical properties. Multiple myeloma manifests more often as light-chain nephropathy. On the other hand, light-chain amyloidosis leads to glomerular and vascular amyloid deposits, but a less common presentation with amyloid casts has also been described. Rarely, more than one histologic pattern can be present in the same patient. Case report: We report a case of a 73-year-old man, diagnosed with multiple myeloma that 8 months after achieving partial response to chemotherapy develops acute kidney injury and nephrotic syndrome. Kidney biopsy revealed features of light-chain nephropathy, amyloid cast nephropathy, and glomerular and vascular amyloid deposits. Immunofluorescence was positive for IgA (++) and lambda chains (+++) and negative for kappa chains. After the diagnosis of multiple myeloma-associated light-chain amyloidosis, chemotherapy was initiated; unfortunately, the patient died 1 month after the diagnosis. Conclusion: Amyloid casts, isolated or accompanied by other renal or extra-renal amyloid deposits, are another form of tubular toxicity caused by dysproteinemias and should be systematically screened in kidney biopsies.

Vancomycin-Associated Cast Nephropathy: Reality or fantasy

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Rare presentation of kappa light chain proximal tubulopathy with fibrillar aggregates

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.

Acute Kidney Injury in Monoclonal Gammopathies

Monoclonal gammopathies (MG) encompass a variety of disorders related to clonal expansion and/or malignant transformation of B lymphocytes. Deposition of free immunoglobulin (Ig) components (light or heavy chains, LC/HC) within the kidney during MG may result over time in multiple types and degrees of injury, including acute kidney injury (AKI). AKI is generally a consequence of tubular obstruction by luminal aggregates of LC, a pattern known as “cast nephropathy”. Monoclonal Ig LC can also be found as intracellular crystals in glomerular podocytes or proximal tubular cells. Proliferative glomerulonephritis with monoclonal Ig deposits is another, less frequent form of kidney injury with a sizable impact on renal function. Hypercalcemia (in turn related to bone reabsorption triggered by proliferating plasmacytoid B cells) may lead to AKI via functional mechanisms. Pharmacologic treatment of MG may also result in additional renal injury due to local toxicity or the tumor lysis syndrome. The present review focuses on AKI complicating MG, evaluating predictors, risk factors, mechanisms of damage, prognosis, and options for treatment.