An atypical cause of amyloidosis: a case of combined heavy and light chain amyloidosis.

backgroundThe International Society of Amyloidosis recognizes 15 types of kidney-related amyloidosis, with most studies identifying immunoglobulin light chain (AL) amyloidosis as the leading cause in over half of these cases. Heavy chain (AH) amyloidosis has been reported in 0.1-2.3% of kidney amyloidosis cases. This case is particularly novel due to the extremely rare occurrence of combined heavy and light chain (AHL) amyloidosis and its uncommon outcome. CASE PRESENTATION: A 78-year-old man with hypertension and hyperlipidemia presented with swelling in both the upper and lower extremities, accompanied by dyspnea. On examination, he had crackles in both lung fields on auscultation. His abdomen was distended, and his upper and lower extremities were noted with + 3 edema. Workup revealed a serum creatinine of 1.25 mg/dL, and serum albumin of 2.7 g/dL, 22 g of proteinuria in a 24-hour collection, high lambda light chains at 3,800 mg/L with kappa/lambda ratio of 0.01, and elevated IgM levels at 3,500 mg/L. A kidney biopsy showed mesangial expansion with negative periodic-acid-Schiff and positive Congo Red Stain with apple-green birefringence under polarized light. Immunofluorescence revealed diffuse mesangial staining for IgM (3+), C3 (2+), and lambda light chains (2+). Mass spectrometry confirmed lambda light chain and mu heavy chain amyloidosis. The patient was diagnosed with AHL amyloidosis with a precursor low-grade B-cell lymphoma with plasmacytic differentiation. Based on these findings, rituximab and bendamustine were started. The patient's condition continued to deteriorate, ultimately progressing to dialysis dependance. Two months after starting dialysis, he chose to transition to hospice care.

conclusionKidney AHL amyloidosis is extremely rare. Diagnosis requires a kidney biopsy and mass spectrometry to identify the amyloidogenic protein, given the highest sensitivity and specificity of this technique and the limitations of immunofluorescence. Compared to AL, AHL patients have a higher prevalence of IgM monoclonal gammopathy, longer overall survival (5-year survival rate of 66%), and less advanced disease. Although data are limited, our case underscores the potential rapid progression to dialysis in kidney AHL amyloidosis patients with high proteinuria at diagnosis.