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The primary glomerulonephritides: a systems biology approach

Nature Reviews Nephrology volume 9, pages 500–512 (2013)Cite this article

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Abstract

Our understanding of the pathogenesis of most primary glomerular diseases, including IgA nephropathy, membranous nephropathy and focal segmental glomerulosclerosis, is limited. Advances in molecular technology now permit genome-wide, high-throughput characterization of genes and gene products from biological samples. Comprehensive examinations of the genome, transcriptome, proteome and metabolome (collectively known as omics analyses), have been applied to the study of IgA nephropathy, membranous nephropathy and focal segmental glomerulosclerosis in both animal models and human patients. However, most omics studies of primary glomerular diseases, with the exception of large genomic studies, have been limited by inadequate sample sizes and the lack of kidney-specific data sets derived from kidney biopsy samples. Collaborative efforts to develop a standardized approach for prospective recruitment of patients, scheduled monitoring of clinical outcomes, and protocols for sampling of kidney tissues will be instrumental in uncovering the mechanisms that drive these diseases. Integration of molecular data sets with the results of clinical and histopathological studies will ultimately enable these diseases to be characterized in a comprehensive and systematic manner, and is expected to improve the diagnosis and treatment of these diseases.

Key Points

  • Novel systems biology techniques that permit comprehensive molecular characterization of biological samples are improving our understanding of the molecular basis underlying primary glomerular diseases

  • Large-scale genomic studies of glomerular diseases have identified genetic loci that are associated with the development of these diseases and have enriched our understanding of their pathogenesis

  • Several novel monogenic forms of focal segmental glomerulosclerosis have been identified, which has improved the classification of hereditary and spontaneous variants of this disease and could potentially influence therapeutic decisions

  • Polymorphisms in APOL1 that increase the risk of developing focal segmental glomerulosclerosis and HIV-associated nephropathy have been identified in African American populations

  • Clinical application of the findings generated from systems-biology-based analysis is currently limited

  • Collaborative efforts for recruiting patients, monitoring clinical outcomes and developing standardized protocols for kidney tissue sampling, are needed to study rare primary glomerular diseases

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Figure 1: Sources of biological material for use in 'omics' studies of primary glomerulonephritides.

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Acknowledgements

S. Jiang, Z.-H. Liu and J. C. He are supported by Chinese 973 fund 2012CB517601NIH. J. C. He is supported by NIH grant numbers 1R01DK088541, 1R01DK078897, P01DK56492 and 1RC4DK090860, and a Veterans Administration Merit Award; P. Y. Chuang is supported by NIH grant number 5K08DK082760.

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Authors and Affiliations

  1. Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, 210002, Nanjing, China

    Song Jiang & Zhi-Hong Liu

  2. Division of Nephrology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, 10029-6574, NY, USA

    Peter Y. Chuang & John C. He

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S. Jiang, P. Y. Chuang, Z.-H. Liu and J. C. He contributed equally to writing the article. Z.-H. Liu and J. C. He also reviewed and edited the manuscript before submission. All authors contributed to researching data for the article and discussions of its content.

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Correspondence to John C. He.

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Jiang, S., Chuang, P., Liu, ZH. et al. The primary glomerulonephritides: a systems biology approach. Nat Rev Nephrol 9, 500–512 (2013). https://doi.org/10.1038/nrneph.2013.129

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