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Robust Research Pipeline Ensures Exquisite Data Quality Control, Paving the Path Toward Personalized Kidney Care

A large team of scientists has developed and tested a robust research pipeline for rigorously collecting and analyzing kidney biopsy samples; these analyses will be essential for catalyzing research toward personalized care for people with kidney diseases. Few therapies are currently available for treating chronic kidney disease and acute kidney injury—two relatively common types of kidney diseases. NIDDK’s Kidney Precision Medicine Project (KPMP) aims to identify previously elusive cells, molecules, and pathways involved in kidney disease progression by harnessing sophisticated research technologies. Ultimately, KPMP’s goals are to construct a high-resolution three-dimensional kidney “atlas,” define kidney disease subgroups, and identify new therapeutic targets, which together will provide a foundation for personalized approaches to kidney care.

A central component of KPMP is the procurement of kidney biopsies from people with and without kidney diseases across multiple U.S. locations. These biopsy samples are then divided and shipped to different laboratories for analysis to identify a range of molecules (e.g., genetic material, proteins, metabolites) and cells in the kidney that are associated with health or diseased states. Importantly, reproducibility of research results across KPMP sites requires standardized processes and high levels of quality control at each step, such as biopsy procurement, preservation, storage, and analysis, as well as data generation and validation. In a recent report, KPMP scientists detailed this enormous collaborative undertaking, in which they carefully developed a series of protocols to generate an integrated “follow the tissue” pipeline that will maximize the information gleaned from the precious biopsy samples. The researchers then tested the pipeline in a pilot experiment using adult human kidney tissue from a single source. The pilot experiment demonstrated that the pipeline was indeed robust and results were reproducible at five laboratories, but did reveal some areas for improvement, such as inconsistencies in temperature states during shipping and the need for some additional surrounding tissue to optimize a particular imaging technique. These issues will be addressed and corrected as the KPMP study moves forward.

The establishment of this robust “follow the tissue” pipeline was essential for KPMP to begin generating rigorous and reproducible data that will accelerate research toward personalized kidney care. This framework could serve as a model for developing organ atlases with limited tissue to advance precision medicine research for other diseases.

El-Achkar TM, Eadon MT, Menon R,…Jain S; for The Kidney Precision Medicine Project. A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: guidelines from the Kidney Precision Medicine Project. Physiol Genomics 53: 1-11, 2020.

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