Evolving clinical applications of tissue transcriptomics in kidney disease

Abstract

Nephrotic syndrome is classically categorized by the histopathology with examples including focal segmental glomerulosclerosis (FSGS) and minimal change disease. Pediatric patients are also classified by whether their nephrotic syndrome is sensitive to, dependent on, or resistant to steroids. However, this traditional classification system overlooks the frequent clinical conundrum when, for example, one patient with FSGS responds briskly to steroids, and another quickly progresses to end stage kidney disease despite therapy. Two patients may have similar histopathologic appearances on kidney biopsy but entirely different clinical characteristics, rates of progression, and treatment responses. Transcriptional regulation of gene activation and posttranscriptional processing of mRNA may drive the unique and heterogeneous phenotypes which are incompletely understood in kidney disease and are a recent focus of research. Gene expression profiles provide insight on active transcriptional programs in tissues, are being used to understand biologic mechanisms of progressive chronic kidney disease, and may help to identify patients with shared mechanisms of kidney damage. This mini-review discusses clinically relevant techniques of bulk tissue and single cell transcriptomics, as well as strengths and limitations of each methodology. Further, we summarize recent examples in kidney research achieved through transcriptomics. This review offers an outlook on the role of transcriptomics in an integrative systems biology model with the goal of defining unique disease subgroups, finding targets for drug development, and aligning the right drug with the right patient.