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Progression of proliferative glomerulonephritis with monoclonal IgG deposits in pediatric patients

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Abstract

Background

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain–restricted immunoglobulin and is rarely reported in children.

Methods

We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition.

Results

Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine. Prodromal or concurrent infection was identified in six patients, low C3 in five, and alternate complement pathway gene variants in two. No monoclonal serum proteins were identified in five tested patients. Seven patients had monotypic deposits composed of IgG3-λ, two showed IgG3-κ, and one each IgG1 and IgG3 with lambda dominance in the setting of IgM deposition. The glomerular pattern was predominantly mesangial proliferative or membranoproliferative glomerulonephritis (MPGN). Treatment and outcomes were variable; four patients have recent PGNMID diagnoses and therefore minimal follow up, one had relatively stable kidney function for over a decade, and six experienced kidney failure, with four receiving transplants. Recurrent deposits of the same isotype were identified in five of six transplanted kidneys, corresponding to three of four transplanted patients. One of these patients developed PGNMID recurrences in three separate kidney allografts over a 20-year disease course.

Conclusions

Our study emphasizes the need for upfront IgG subclass investigation in pediatric mesangial or MPGN with IgG deposition and monotypic or biased light-chain staining. Furthermore, this pediatric experience suggests expanded pathogenic considerations in PGNMID.

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Data availability

Detailed histopathologic data from all biopsies are provided as supplementary table (online resource 1).

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Acknowledgments

The authors acknowledge the expert technical assistance of the histology, immunofluorescence, and electron microscopy laboratories at Cedars-Sinai, Stanford, and UCSF. Norm Cyr, graphic artist, assisted with the creation of Figs. 1, 2, and 3.

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Author notes

  1. Paul Miller and Andrew Y. Xiao contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, L235, Stanford, CA, 94305, USA

    Paul Miller, Andrew Y. Xiao, Richard K. Sibley, John P. Higgins, Neeraja Kambham, Vivek Charu & Megan L. Troxell

  2. Oakland University William Beaumont School of Medicine, Rochester, MI, USA

    Andrew Y. Xiao

  3. Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA, USA

    Vanderlene L. Kung & Cynthia C. Nast

  4. Stanford Adult Kidney Transplant Program, Stanford, CA, USA

    Colin Lenihan

  5. Department of Pediatrics (Nephrology), Stanford University School of Medicine, Stanford, CA, USA

    Amanda M. Uber & Elizabeth M. Talley

  6. Department of Nephrology, The Permanente Medical Group Northern California, Oakland, CA, USA

    Neiha Arora

  7. Department of Pathology, University of California San Francisco, San Francisco, CA, USA

    Vighnesh Walavalkar & Zoltan G. Laszik

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  1. Paul Miller
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Contributions

Megan Troxell, Neeraja Kambham, Colin Lenihan, and Cynthia Nast contributed to the study conception and design. All the authors contributed to the data collection. Data tabulation and analysis was performed by Paul Miller, Andrew Xiao, Vanderlene Kung, and Megan Troxell. The first draft of the manuscript was written by Paul Miller, Andrew Xiao, and Megan Troxell. All the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Megan L. Troxell.

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Conflict of interest

Dr. Amanda Uber is a Paul and Yuanbi Ramsay Endowed Fellow, Maternal and Child Health Research Institute at Stanford.

None of the other authors have conflicts of interest to declare.

Ethics approval

This study received Institutional Review Board approval at Stanford and Cedars-Sinai, and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Not applicable (HIPAA waiver for retrospective study).

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Not applicable (HIPAA waiver for retrospective study).

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Miller, P., Xiao, A.Y., Kung, V.L. et al. Progression of proliferative glomerulonephritis with monoclonal IgG deposits in pediatric patients. Pediatr Nephrol 36, 927–937 (2021). https://doi.org/10.1007/s00467-020-04763-5

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  • DOI: https://doi.org/10.1007/s00467-020-04763-5

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