Introduction:
Immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) is an ultra-rare, fast-progressing kidney disease resulting from immunoglobulin/immune complex deposition triggering complement activation. Data regarding clinical course and long-term outcome in children with IC-MPGN is still scarce. The aim of the study was to investigate clinical and histopathological characteristics and kidney outcomes in children with primary IC-MPGN.
Methods:
We conducted retrospective study of 19 (8M/11F) children with IC-MPGN diagnosed between 2012 and 2019 years. The median age at onset of the disease was 11.0 (IQR: 8.0; 14.0) years. The median duration of the disease before kidney biopsy was 6.0 (IQR: 3.5; 14.0) months. Kidney biopsy with light microscopy and immunofluorescence was performed in all patients. Electron microscopy was done in 11/19 (57.9%) children. All patients were treated with intravenous (iv) cyclophosphamide (CYC) at a dose of 500 mg/m2 for monthly infusion for 6 months combined with oral steroids (1 mg/kg/48h). The median follow-up was 24.0 (IQR: 15.6; 46.8) months.
Results:
All patients presented with steroid-resistant nephrotic syndrome (SRNS) with hematuria and hypertension. 7 (36.8%) children had elevated serum creatinine level at onset of IC-MPGN. Light microscopy revealed along with glomerular basement membrane double contours accompanied by endocapillary and mesangial hypercellularity in all cases, focal glomerulosclerosis in 14 (73.7%) patients, tubular dystrophy and atrophy in 14 (73.7%) and 5 (26.3%) patients, respectively, and interstitial fibrosis in all subjects, including focal - in 15 (78.9%) and diffuse - in 4 (21.1%) individuals. Immunofluorescence showed capillary loop and mesangial deposition of IgG with or without IgM and, to a lesser extent, C3 in all individuals. Electron microscopy demonstrated thickening of glomerular capillary walls due to subendothelial deposition of immune complexes with diffuse (6/11 (54.6%)) or focal (5/11 (45.4%)) podocyte effacement. The first line of immunosuppressive treatment with iv CYC induced complete (CR) and partial remission (PR) of IC-MPGN in 5 (26.3%) and 4 (21.1%) patients, respectively. There was no effect of CYC treatment in 10 (52.6%) children. At the end of follow-up CKD-1 was found in 7 (36.8%) patients with IC-MPGN; CKD-2 in 7 (36.8%) children; CKD-3 in 4 (21.1%) subjects, and CKD-5 in 1 (5.3%) case. Increase in eGFR slope during follow up had 8 (42.1%) children (median 6.0 (IQR: 11.4; 1.8) ml/min/1.73 m2 per year). Decrease in eGFR slope during follow up found in 11 (57.9%) patients (median -4.6 (IQR: -1.4; - 13.4) ml/min/1.73 m2 per year).
Conclusions:
All children with IC-MPGN presented with SRNS with hematuria and hypertension. CYC iv induced CR and PR in almost half of patients, while progression to CKD-2-5 was found in other half of children with IC-MPGN. Effective targeted anti-complement therapy is urgently needed to prevent progression of IC-MPGN to CKD in children.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.