Clinicopathological characteristics of light chain proximal tubulopathy: a multicentre case series.

Abstract

Aims: Light chain proximal tubulopathy (LCPT) is a rare complication of paraprotein-related diseases. We report a case series to present the clinicopathological characteristics and outcomes of LCPT.

Methods: A multicentre retrospective case series of 47 patients with LCPT, consisting of 36 crystalline, three non-crystalline, and eight mixed LCPTs, was studied between January 2007 and December 2023.

Results: The median age at diagnosis was 57 years. Presentations included proteinuria (100%), renal insufficiency (62%) and Fanconi syndrome (68%). The underlying haematological diagnoses were monoclonal gammopathy of renal significance in 81% and multiple myeloma in 19%. Monoclonal light chain (LC) was detected in all cases using serum/urine-free LC assays or immunofixation electrophoresis. Among 36 crystalline LCPTs, 34 were κ-restricted and 2 λ-restricted. Three non-crystalline LCPTs were all λ-restricted. In mixed LCPTs, seven were κ-restricted and one was λ-restricted. Notably, 66% frozen-section immunofluorescence failed to reveal restricted LC, requiring paraffin-immunofluorescence or immunoelectron microscopy. The appearance of inclusions displayed intraindividual homogeneity but interindividual heterogeneity in 42 patients and notable intraindividual heterogeneity in the remaining 5 patients. Haematological complete response, very good partial response and partial response occurred in 61%. Kidney function improved or remained stable in 84%, worsened in 8% and progressed to end-stage renal disease in 8%.

Conclusions: Proteinuria and kidney dysfunction are the most common but less-specific renal manifestations of LCPTs, with most featuring Fanconi syndrome. Crystalline LCPT, primarily associated with κ-LC, is the predominant form. Most inclusions displayed intraindividual homogeneity and interindividual heterogeneity by electron microscopy. Most achieved haematological responses and favourable renal outcomes.