Project description:Calcium oxalate stones account for over 80% of urinary stones, while the molecular mechanism of its formation is still not completely elucidated. The incidence of hyperoxaluria in calcium oxalate stone formation ranks only second to hypercalciuria. It plays an important role in the pathophysiological process of stone formation. We analyzed miRNA expression profiles between experimental hyperoxaluric rats and normal rats in order to find out the target genes and signaling pathways in the pathogenesis of hyperoxaluria.
Project description:Kidney stone disease causes significant morbidity and increases health care utilization. The pathogenesis of stone disease is incompletely understood, due in part to the poor characterization of the cellular and molecular makeup of the human papilla and its alteration with disease. In this work, we characterize the human renal papilla in health and calcium oxalate stone disease using single nuclear RNA sequencing, spatial transcriptomics and high-resolution large scale multiplexed 3D and Co-Detection by indexing (CODEX) imaging. We define and localize subtypes of principal cells enriched in the papilla as well as immune and stromal cell populations. We further uncovered an undifferentiated epithelial cell signature in the papilla, particularly during nephrolithiasis.
Project description:Kidney stone disease causes significant morbidity and increases health care utilization. In this dataset, we applied a single-nucleus assay to renal papila samples in order to charachterize the cellular and molecular niches in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.
Project description:Accumulation of oxalate in patients with chronic kidney disease (CKD) is associated with CKD progression and an increased risk of cardiac death. Whether reducing oxalate slows CKD progression and prevents cardiovascular complications remains unexplored. We colonized Oxalobacter formigenes (Oxf), an oxalate-degrading microbiome, in the intestines of control and CKD mice fed with 1% hydroxyproline for 23 weeks. RNA-seq analysis of heart tissues of CKD mice reveals dysregulated expression of metabolic pathways and Oxf colonization reverses these changes. These findings demonstrate that oxalate accumulation plays a role not only in CKD progression but also in cardiovascular complications.
2025-06-16 | GSE297087 | GEO
Project description:Gut microbiome and oxalate-related metabolic functions in staghorn calcium oxalate stones formers
Project description:We evaluated the impact of spaceflight on a microphysiologic model of calcium oxalate (CaOx) kidney stone disease. Proximal tubule epithelial cells cultured as confluent microtubules were exposed to CaOx crystals with or without potassium citrate (a potential countermeasure) to determine impact on gene expression. Nine genes were differentially expressed in response to CaOx crystal exposure during spaceflight. This project presents the use of microgravity as a unique environment to study kidney pathophysiology.
Project description:Randall’s plaque (RP) is the origin of renal calcification on which idiopathic calcium oxalate (CaOx) kidney stones develop. To establish genomic pathogenesis of RP, we performed the microarray analysis for comparing the gene expressions among renal papillary RP and normal tissue of 23 CaOx and 6 calcium phosphate (CaP) stone formers, and normal papillary tissue of 7 control patients. Compare to normal papillary tissue, RP tissue contained up-regulation of lipocalin 2, interleukin 11, prostaglandin-endoperoxide synthase 1, glutathione peroxidase 3, and monocyte to macrophage differentiation, whereas down-regulation of solute carrier family 12 member 1 and sodium leak channel non selective (either > 2.0- or 0.5-fold, p <0.01). The network and toxicity analysis showed these genes had association with activated mitogen-activated protein kinase, Akt/ phosphatidylinositol 3-kinase pathway, and pro-inflammatory cytokines, which caused renal injury and oxidative stress.
Project description:<p>Background: The incidence and recurrence rate of nephrolithiasis have been increasing annually. Recent evidence highlights a close association between the composition and function of the gut microbiome and the occurrence and recurrence of kidney stones. We performed a multi-omic study to investigate changes in gut microbiota and their metabolites during nephrolithiasis development and recurrence, and to explore the underlying molecular mechanisms. Fecal samples from 37 recurrent stone patients, 38 first-episode stone patients, and 39 healthy controls were collected for 16S rDNA amplicon sequencing and liquid chromatography-mass spectrometry. Ten samples from each group were randomly selected for metagenomic sequencing.</p><p>Results: Compared to incident cases, recurrent stone patients exhibited further reduced gut microbial richness and diversity, with enrichment of Enterobacterales, Pseudomonadota, Gammaproteobacteria, Enterobacteraceae, Escherichia-Shigella, and Bacillia. In the recurrent kidney stone group, 9 metabolites were upregulated and 86 downregulated, primarily enriched in purine metabolism, and caffeine metabolism pathways. We identified 10 metabolites as recurrence biomarkers and found significant correlations between Escherichia-Shigella and Asn-Tyr, Leu-Ala-Ile, Tyrosyl-Alanine, or 3'-hydroxyhexobarbital. Additionally, gender-specific gut microbiota signatures were observed. Oxalate decarboxylase and short-chain fatty acid-related enzymes decreased during stone formation but rebounded with recurrence. Caffeine and its metabolites were significantly downregulated in recurrent patients, suggesting a potential association with stone formation and recurrence that merits further investigation.</p><p>Conclusions: Our study comprehensively characterizes the gut microbiome and metabolome signatures associated with nephrolithiasis recurrence. The findings reveal that recurrent nephrolithiasis is characterized by impaired gut microbial evenness, enrichment of specific taxa including Escherichia-Shigella, and dysregulated metabolic pathways such as purine metabolism and caffeine metabolism. The 10 identified metabolites show promise as potential recurrence biomarkers, with notable correlations between Escherichia-Shigella and key metabolites. These results highlight the critical association of the gut microbiome-metabolome axis with renal stone recurrence, providing novel microbial and metabolic targets for early prediction, with potential implications for prevention and personalized treatment that require further validation.</p>