Quantitative Morphometry of Research Kidney Biopsies and Transcriptomic Analysis of Tissue from Research Kidney Biopsies

The Chronic Kidney Disease Section focuses on the mechanisms of diabetic kidney disease. Our work has focused on adults with type 2 diabetes, but recent studies indicate that youth who develop type 2 diabetes may have a far more aggressive course of diabetic kidney disease than their adult counterparts. Accordingly, we wish to study persons with youth onset type 2 diabetes and compare their kidney structure and transcriptomic profile with those of the adults we have already studied and to also compare them with youth onset type 1 diabetes.

Therefore, we have established a collaboration with Dr. Peter Bjornstad at the University of Colorado, who is the only researcher to acquire kidney tissue in youth with youth-onset type 2 diabetes and to establish a detailed clinical phenotype in the same individuals. Dr. Bjornstad has presently conducted over 100 studies of intrarenal hemodynamic function combined with state-of-the-art functional magnetic resonance imaging in youth, including those with type 1 or type 2 diabetes.

Transcriptomics technologies offer an organizational and methodological platform to identify key genes and pathways involved in early diabetic kidney disease. The maturation of various integrative biology approaches is already contributing to research capabilities, and this is expected to expand. However, crucial components of the future success of these endeavors are deep clinical phenotyping and access to renal tissue. Molecular pathways identified in this study will be validated in model systems (e.g. human organoids and murine models) and leveraged as starting points for future drug development. Finally, data generated from this project will be used to direct and design a longitudinal multicenter center study that will define pathological and molecular features of early diabetic kidney disease and its progression in youth with diabetes.

The goal of this project is for the first time to comprehensively detail morphometric, molecular, metabolic and energetic patterns of early diabetic kidney disease in youth. Tissue obtained from these biopsies will be sent to the University of Michigan where they will undergo quantitative morphometry and RNA sequencing studies performed either in single cell preparations or in the glomerular and tubulointerstitial compartments after microdissection.

In this acquisition, we will acquire the services needed to perform quantitative morphometry on an additional 14 research kidney biopsies acquired at the University of Colorado. The morphometric work will be performed at the University of Michigan. Data and results from these studies will be shared with NIDDK and NIDDK investigators will be authors on all publications emanating from this work.

We wish to examine the underlying mechanisms responsible for the development of diabetic kidney disease in persons with youth onset disease. We do not have access to this patient population locally, but we can compare findings in our adult population with those from this youth onset population.

By adding a second component to the study, on the same patients, makes it pertinent to use the same vendor for ensuring consistency and reproducibility of our study. Furthermore, it would be difficult to compare the results from the first part of the study with the second part without using the same vendor. Prior work done, allows this vendor access to unique proprietary information.

Awarded contract 75N94020P00336 to unknown vendor for unknown amount on 2020-04-27.