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Integrated systems biology to define renal disease

To take advantage of the rapidly emerging approaches in genomic medicine to define disease on the molecular level, cohorts of patients with large-scale molecular and clinical data sets on the same individual are be the rate-limiting step. Establishing these cohorts requires a long-term effort, but renal disease offer a unique advantage compared to other chronic diseases as we have access to the primary disease mechanism in humans via renal biopsy and urine derived biofluids.

Technologies are emerging to obtain comprehensive genome wide information spanning genotype, tissue compartment specific epigenetic, transcriptional, proteomic and metabolomic datasets from blood, urine and renal tissue. Matching this information with in vivo imaging, digital histopathology and prospective clinical disease course including drug and environmental exposures can aid to define underlying molecular events of phenotypic measures. Systems biology approaches can be employed across the entire genotype – phenotype continuum to redefine renal diseases on the molecular level and identify the key regulatory hubs most amendable to therapeutic manipulations. These data sets will be a reference base to test novel hypotheses and model systems for human disease relevance.


Submitted by Matthias Kretzler 3 years ago

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(latest 20 votes)


  1. The Idea titled National programs for rare forms of GN was merged with this Idea
    2 years ago

Comments (11)

  1. Pinned Moderator

    Many of the clinical and biology questions in this category have a common theme ie the rarity of these conditions and the difficulty in implementing a standardized system for the collection of biologic samples but in concert with the clinical information since one without the other is ofmited value

    3 years ago
  2. Michael Braun Merged

    The development of treatment protocols, and studies in pathogenesis of rare forms of GN are hampered by a lack of sufficient power. These diseases can get lost because of "lack of impact" in terms of overall public health. Programmatic structures to foster collaborative multicenter or national networks is needed.

    3 years ago
  3. Development of centers of excellence is paramount for the collection, study and translational aspects of these diseases (like aHUS and DDD). There is so much to be done- collaborative approaches are the only way we will make headway with these types of diseases.

    3 years ago
  4. Moderator

    Agree, but would emphasize the importance of intelligent analysis of these large datasets over their collection!

    3 years ago
  5. I think the collaborative multicenter/national networks should not be limited to the "rare forms" of GN, but be inclusive of all GN, as progress in understanding and managing even the "major" forms of GN has been hampered by the relative small number of patients at any one site.

    3 years ago
  6. Matthias Kretzler Idea Submitter

    Strongly support the concept, we have to transition as a community to consider each patient seen a study patient, otherwise this will remain the rate limiting step for T1 in renal disease.

    Costs might not be as prohibitive as envisioned, as core infrastructure elements should most likely be genuine for all research networks and could be shared between projects.

    3 years ago
  7. Matthias Kretzler Idea Submitter

    Certainly, analysis tools are effectively employed in model systems and are currently scaled up to mammals in the 'big disease categories'. They should be transferable to renal disease if we establish cohorts and train our next generation in these approaches.

    3 years ago
  8. I really want to support this concept, and believe the ideas expressed by Patrick and Matthias are very important to achieving success. I believe the ASN, and other kidney organizations, can be and should be enlisted to partner with the NIH to foster development of an infrastructure for studies of all types of Glomerular Disease (GD). This infrastructure will need to be multi-institutional in order to enroll sufficient patients that clinical studies and even interventional trials taking advantage of this patient base can have robust numbers of cases.

    3 years ago
  9. I fully agree with the approach described. Recent findings in glomerular disease suggest that GWAS studiescan also provide very important information in small cohorts of well phenotyped patients. Pangenomic studies are nice adjuncts to integrative biology performed on tissues

    3 years ago
  10. Moderator

    Matthias and Pat, please see my related suggestion, just uploaded, about a specific area for application, regarding phenotyping cells and tissue (in the Other section). I think this approach could be very helpful for relating hypothesis-based studies and results from newer, "unsupervised approaches to understanding disease pathogenesis and treatment, and not just for glomerular disease.

    3 years ago
  11. These are all important ideas. But I would like to add that there is a great need to advance biotechnologies and computational tools (software, bioinformatics, mathematical modeling and visualization) to interrogate pathways associated with renal disease. Greater efforts are needed to foster collaborations between computer scientists, mathematicians, physicists, engineers and renal investigators. In that regards, grant opportunities between different NIH institutes would be one way to stimulate innovative multidisplinary teams to address enormous challenges of progressive renal disease.

    3 years ago