Cellular and molecular interrogation of kidney biopsy specimens

Abstract

Purpose of review: Traditional histopathology of the kidney biopsy specimen has been an essential and successful tool for the diagnosis and staging of kidney diseases. However, it is likely that the full potential of the kidney biopsy has not been tapped so far. Indeed, there is now a concerted worldwide effort to interrogate kidney biopsy samples at the cellular and molecular levels with unprecedented rigor and depth. This review examines these novel approaches to study kidney biopsy specimens and highlights their potential to refine our understanding of the pathophysiology of kidney disease and lead to precision-based diagnosis and therapy.

Recent findings: Several consortia are now active at studying kidney biopsy samples from various patient cohorts with state-of-the art cellular and molecular techniques. These include advanced imaging approaches as well as deep molecular interrogation with tools such as epigenetics, transcriptomics, proteomics and metabolomics. The emphasis throughout is on rigor, reproducibility and quality control.

Summary: Although these techniques to study kidney biopsies are complementary, each on its own can yield novel ways to define and classify kidney disease. Therefore, great efforts are needed in order to generate an integrated output that can propel the diagnosis and treatment of kidney disease into the realm of precision medicine.

Figure 1:

Technology integration in the KPMP. Schematic of integration of various technologies used in the KPMP consortium at the various biological units within the kidney: cells, structures, entire biopsy specimens. Single cell single nuclear RNA sequencing: Sc/snRNA seq; Assay for Transposase-Accessible Chromatin using sequencing: ATAC-seq; Digital Pathology: Digital Path; Co-detection by Indexing: CODEX; Spatial transcriptomics: ST; Imaging mass cytometry: IMC.