Clinicopathologic and Prognostic Study of Primary IgA Nephropathy With Light Chain λ Restriction in the Mesangial Deposits

Abstract

Introduction: Primary IgA nephropathy (IgAN) with light chain λ restriction in the mesangial deposits (IgAN-λ) has unique immunofluorescence (IF) features. Nevertheless, its clinicopathology and prognosis are still ambiguous.

Methods: From January 2002 to December 2020, the clinical and pathologic data of 3872 patients who were diagnosed with having primary IgAN by renal biopsy in our hospital were reviewed. A total of 187 patients who met the selection criteria for IgAN-λ were enrolled to conduct a retrospective single-center study. The selection criteria were that IF features conform to light chain λ restriction in the mesangial deposits. According to age, sex, renal function (estimated glomerular filtration rate [eGFR]), and follow-up time, the control group was constructed with 1:3 matched cases of IgAN. The clinicopathologic and prognostic differences between the 2 groups were analyzed.

Results: Compared with that in the IgAN group, the serum fibrinogen level in the IgAN-λ group was significantly higher (P < 0.001). Furthermore, cluster analysis indicated the different clusters involved in fibrinogen between the IgAN-λ and IgAN groups and that fibrinogen is associated with factors reflecting renal function in IgAN-λ but proteinuria levels in IgAN. The light chain λ deposit in the mesangium is associated with the formation of crescents in those with IgAN-λ, but complement C3 deposition in those with IgAN. Our Kaplan-Meier analysis revealed that the prognosis of the IgAN-λ group was significantly worse than that of the IgAN group within >6 years of follow-up (P = 0.02). The multi-Cox analysis revealed that the light chain λ restriction in the mesangial deposits was an independent risk factor for poor outcomes (eGFR decreased from the baseline ≥ 30% continuously or reached end-stage renal disease [ESRD] or died).

Conclusion: The prognosis of those with IgAN-λ was worse than that of those with IgAN, which may be attributed to the light chain λ restriction in the mesangial deposits inducing a significant systemic inflammation manifested as severe clinical features and frequent crescent.

Keywords: IgA nephropathy; clinicopathology; kidney disease; light chain λ; prognosis.

Graphical abstract

Figure 1

Cluster analysis for clinical factors between the groups. (a) The heatmaps display the correlation coefficient (Pearson’s correlation coefficient for linear data) of the clinical factors in IgAN-λ and IgAN. The color label under the heatmap reveals that the red shade represents a positive correlation whereas the blue shade represents a negative correlation. The related factors shared the same or similar colors. (b) The network diagram displays the clinical factors’ clustering relationship in IgAN-λ and IgAN. The nodes represent the factors, and the shapes of the nodes represent the groups (circle for IgAN-λ and square for IgAN). The nodes connected by a solid black line reveal a stronger correlation and construct a cluster whereas the nodes connected by the solid gray line are the same factors from the different groups (the same factors are assigned a tiny weight, and different factors are assigned the same larger weight). The clusters, including the factor “Fibrinogen” of the 2 groups, are chosen to make cluster analysis by using the heatmap. (c) The mosaic plots display the relationships between levels of fibrinogen and CKD score/proteinuria levels in the 2 groups. The size of boxes is proportional to the frequency of each item. The shadings are made based on the Pearson residuals that were calculated by the R package of vcd. The blue shades represent high residuals whereas red shades mean the opposite. Alb, serum albumin; BMI, body mass index; BU, blood urea; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; H, high; Hb, hemoglobin; HDL, high-density lipoprotein; IgAN-λ, IgAN with light chain λ restriction in the mesangial deposits; IgAN, primary IgA nephropathy; L, low; LDL, low-density lipoprotein; M, medium; MBP, mean blood pressure; s-Cr, serum creatinine; sκ, serum light chain κ; sλ, serum light chain λ; TC, total cholesterol; TG, triglyceride; UA, uric acid.

Figure 2

Comparison of prognosis between IgAN group and IgAN-λ group (Kaplan–Meier curve), P = 0.02 (log-rank test). The end point is the eGFR 30% decrease of the baseline or reaching end-stage renal disease or death. e-GFR, estimated glomerular filtration rate; IgAN-λ, IgAN with light chain λ restriction in the mesangial deposits; IgAN, primary IgA nephropathy.