Immunological Monitoring of Plasma Exchange in Primary IgA Nephropathy

Abstract

Plasma exchange (PE) has recently been proposed for primary immunoglobulin (Ig)-A nephropathy (PIgAGN) with progressive course. To develop suitable guidelines for PE in these cases, the authors evaluated the clinical usefulness of some immunological parameters in five patients with PIgAGN treated with PE combined with immunosuppressive drugs and small doses of corticosteroids. These parameters included the levels of IgA-containing immune complexes (IgAIC) by a specific conglutinin assay, the function of the mononuclear phagocyte system (MPS) by the in vivo clearance of IgG-sensitized erythrocytes, and complement activation as determined by C3d measurement. HLA types were also determined. Three patients had an acute nephritic syndrome with a rapidly progressive course, one of them showing sclerotic histologic changes. The two other cases had a relentless progression toward renal failure. In the patient with sclerotic PIgAGN, the MPS function was normal and the IgAIC and C3d levels were low throughout the treatment. In the other four cases, the high IgAIC and C3d levels and the MPS dysfunction found before treatment markedly improved after several PEs. The immunological parameters remained normal during the post-PE follow-up in two cases with acute nephritic syndrome and rapidly progressive course, but worsened again in two cases with a relentless course, particularly in one who possessed the B8/DR3 HLA type. Immunological monitoring including IgAIC, C3d, and MPS function is proposed, in addition to histological and clinical evaluation, as a guideline for PE in PIgAGN with evolving course.

Modulation of Mesangial Cell Reactivity by Aberrantly Glycosylated IgA

“…Complement is a crucial mediator of renal injury in experimental models of IgAN [41], and signs of alternative complement pathway activation have been demonstrated in patients with IgAN and Henoch-Schönlein purpura nephritis [42]. The process has been considered to be antigen mediated [43].…”

C4d deposits in IgA nephropathy: where does complement activation come from?

“…In previous studies conducted at our institution we detected increased levels of complement-fixing KIgAIC in patients with active IgAN, with the levels of KIgAIC being significantly correlated with C3d levels [18]. Of interest, in a study of patients with progressive IgAN treated with plasma exchange, the clinical benefits corresponded with a decrease in KIgAIC and complement breakdown products [19].…”

Plasma Exchange as an Adjunctive Therapy for Crescentic IgA Nephropathy

“…Case reports and case series from previous decades have addressed the PE treatment of IgAN patients with rapidly progressive kidney failure and crescent formation on renal biopsy (online suppl. table S2) [9][10][11][12][13][17][18][19][20][21] . Coppo et al [9] studied the effects of PE in 5 patients with progressive IgAN and found that PE delayed disease progression in the 3 patients with crescent formation, but did not delay progression in the patients with advanced sclerotic lesions [13] .…”

“…table S2) [9][10][11][12][13][17][18][19][20][21] . Coppo et al [9] studied the effects of PE in 5 patients with progressive IgAN and found that PE delayed disease progression in the 3 patients with crescent formation, but did not delay progression in the patients with advanced sclerotic lesions [13] . In another 2 reports, PE treatment successfully restored kidney function in a child with CreIgAN and rapid renal function deterioration despite intravenous methylprednisolone therapy [10,22] .…”

“…However, there is only poor-quality evidence to support the use of PE in CreIgAN. One anecdotal report indicated a benefit of PE in combination with immunosuppressive therapies in 5 IgAN patients [9] . Furthermore, this has been confirmed in other case reports [10][11][12][13] .…”