Abstract
Serum uric acid is an end-product of purine metabolism. Uric acid concentrations in excess of the physiological range may lead to diseases such as gout, cardiovascular disease, and kidney injury. The kidney includes a variety of cell types with specialized functions such as fluid and electrolyte homeostasis, detoxification, and endocrine functions. Two-thirds of uric acid is excreted through kidney, however, the exploration of markers and new therapeutic targets in renal tissue of hyperuricemia is still lacking. Single-cell and spatial omics techniques represent major milestones in life sciences. The combined measurement of the physical structure and molecular characteristics of tissues facilitates the exploration of the pathophysiological processes underlying disease development and the discovery of possible therapeutic targets. Here, the spatiotemporal atlas of hyperuricemic nephropathy was investigated using single-cell RNA sequencing, spatial transcriptomics, spatial proteomics, and spatial metabolomics in a urate oxidase knockout mouse model. Several emerging targets and pathways especially ribosome and metabolism related to uric acid excretion were discovered and will be investigated further in studies on lowering uric acid.