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

Ji Zhang; Ziyuan Huang; Sishi Lin; Ya Hu; Yan Liang; Wenxian Qiu; Bo Chen; Chaosheng Chen

doi:10.1016/j.ekir.2022.01.1053

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

Kidney Int Rep. 2022 Jan 26;7(4):776-785. doi: 10.1016/j.ekir.2022.01.1053. eCollection 2022 Apr.

Authors

Ji Zhang^{1

2}, Ziyuan Huang^{1

2}, Sishi Lin^{1

2}, Ya Hu^{1

2}, Yan Liang^{1

2}, Wenxian Qiu^{1

2}, Bo Chen^{1

2}, Chaosheng Chen^{1

2}

Affiliations

¹ Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
² Institute of Chronic Kidney Disease, Wenzhou Medical University, Wenzhou, Zhejiang, PR China.

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.