Crystalglobulin-associated nephropathy presenting as MGRS in a case of monoclonal B-cell lymphocytosis: a case report

Abstract

Background: Crystalglobulin-associated nephropathy (CAN), a rare subtype of monoclonal gammopathy, usually associated with multiple myeloma and occasionally monoclonal gammopathy of uncertain significance (MGUS), is characterized by occluding monoclonal pseudothrombi within renal glomerular capillaries and/or interstitial arterioles. Ultrastructurally, these pseudothrombi are unique for having a crystalline substructure. We describe a case of an adult patient with monoclonal B-cell lymphocytosis (MBL) and acute renal failure whose kidney biopsy revealed a rare diagnosis of CAN. Case presentation: A 63-year old male presented with a 2-month history of edema, arthralgia and malaise. He had acute kidney injury with hematoproteinuria on urine analysis. Serum and urine protein electrophoresis were both negative. A renal biopsy however revealed features of CAN. Organomegaly, bone pain and lymphadenopathy were absent. A repeat serum electrophoresis was positive for IgA kappa and a free light chain assay showed elevated free kappa light chains. Flow cytometry done subsequently revealed a diagnosis of MBL, chronic lymphocytic leukemia (CLL) type. Conclusion: CAN in association with MBL/CLL has not been previously described in literature, and our case highlights yet another instance of monoclonal gammopathy of renal significance (MGRS) where a small B-cell clone resulted in extensive renal pathology without systemic manifestations.

The Crystalline Nephropathies

“…Patients with a dysproteinemia may also develop the rare but interesting disorder known as crystalglobulinemia (70)(71)(72)(73). The formation of microcrystals within the systemic blood vessels and vasculature of the kidneys in these crystalline disorders lead to vascular injury with thrombosis/occlusion and end-organ damage (18,(70)(71)(72)(73). In addition, crystals from these disorders may be seen within the tubular lumens.…”

“…Increased serum creatinine and albuminuria along with various systemic manifestations such as arthralgias and rash characterize the clinical presentation (70)(71)(72)(73)(74). Urinalysis reveals hematuria and proteinuria, while kidney histology demonstrates crystal deposition within vasculature and glomerulus, although intratubular crystals have also been described (70)(71)(72)(73).…”

“…Crystals have geometric shapes that fracture and stain eosinophilic on H&E(Figure 3D), red on trichrome, pink on JS, and pale on PAS (18,(70)(71)(72)(73). Proliferative glomeruli may be present when leukocytes and monocytes engulf crystals (18,(70)(71)(72)(73). IgG kappa-or lambda-restricted staining is noted on immunofluorescence, while crystals are dense with parallel linear array substructure on electron microscopy (18,(70)(71)(72)(73).…”

“…As with all of the dysproteinemias, management hinges on treating the clonal disorder to reduce paraprotein production, while employing plasma exchange to rapidly remove circulating paraproteins is recommended for this disorder (70)(71)(72)(73). Unfortunately, limited data note a relatively poor prognosis with high fatality rate.…”

“… 70 , 71 , 72 , 73 The formation of microcrystals within the systemic blood vessels and vasculature of the kidneys in these crystalline disorders leads to vascular injury with thrombosis/occlusion and end-organ damage. 18 , 70 , 71 , 72 , 73 In addition, the crystals from these disorders may be found within the tubular lumens.…”