Abstract
Simple Summary Cystic renal disease (CRD) is a group of diseases characterized by abnormal sacs, or cysts, in the kidneys. CRD can be detected using certain imaging modalities (i.e., ultrasound). Patients with CRD might be symptoms-free, while others can show symptoms long after cysts development. Although these cysts represent structural changes, we hypothesized that they have an underlying biochemical alteration. If so, this would open the floor for potential biomarker discovery, which would aid in CRD diagnosis and, possibly, treatment. On that basis, this study focuses on identifying biomarkers for CRD. To achieve that, we employed a metabolomics-based approach to identify intermediate molecules inside the cells that are byproducts of biochemical reactions. We used dry blood spots and serum samples of CRD patients and healthy controls to study the differences in their metabolomic profile. Our results suggest that certain metabolites, including uridine diphosphate, cystine-5-diphosphate, and morpholine, are potential biomarkers for CRD. The affected biochemical pathways in CRD include aminoacyl-tRNA biosynthesis, purine, pyrimidine, glutathione, TCA cycle, and some amino acid metabolism. These preliminary results could be the starting point for possible diagnostic and therapeutic approaches for CRD in the future. Cystic renal disease (CRD) comprises a heterogeneous group of genetic and acquired disorders. The cystic lesions are detected through imaging, either incidentally or after symptoms develop, due to an underlying disease process. In this study, we aim to study the metabolomic profiles of CRD patients for potential disease-specific biomarkers using unlabeled and labeled metabolomics using low and high-resolution mass spectrometry (MS), respectively. Dried-blood spot (DBS) and serum samples, collected from CRD patients and healthy controls, were analyzed using the unlabeled and labeled method. The metabolomics profiles for both sets of samples and groups were collected, and their data were processed using the lab's standard protocol. The univariate analysis showed (FDR p < 0.05 and fold change 2) was significant to show a group of potential biomarkers for CRD discovery, including uridine diphosphate, cystine-5-diphosphate, and morpholine. Several pathways were involved in CRD patients based on the metabolic profile, including aminoacyl-tRNA biosynthesis, purine and pyrimidine, glutathione, TCA cycle, and some amino acid metabolism (alanine, aspartate and glutamate, arginine and tryptophan), which have the most impact. In conclusion, early CRD detection and treatment is possible using a metabolomics approach that targets alanine, aspartate, and glutamate pathway metabolites.