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Evaluating Urinary miRNAs as Potential Biomarkers of Chronic Kidney Disease

Chronic kidney disease (CKD) is a significant global health concern, leading to high morbidity and mortality rates and straining healthcare systems worldwide. The rise in CKD cases over recent decades is primarily attributed to the rising prevalence of type 2 diabetes, obesity, and hypertension. Currently, tissue biopsy-based histopathology is the gold standard for assessing kidney damage severity. While accurate, this invasive procedure has prompted ongoing research efforts to identify minimally invasive liquid biopsy-based biomarkers in biofluids like blood and urine that have the sensitivity and specificity needed to enable earlier detection of CKD and facilitate characterization of the underlying pathophysiology.

Micro-RNAs (miRNAs) are short non-coding RNA sequences that function as post-transcriptional regulators of various physiological processes in health and disease. Studies have demonstrated altered miRNAs in urinary extracellular vesicles (EVs) associated with renal pathologies, hinting at their potential as CKD diagnostic biomarkers. Recently, Petzuch and Colleagues investigated the potential of urinary miRNAs as biomarkers by evaluating the urinary miRNA profiles in two rat CKD models that arise from distinct primary pathophysiologic mechanisms: metabolic syndrome (ZSF1) or hypertension (RenTG(mRen2)27). Additionally, mechanistic in vitro investigations using primary human renal proximal tubule epithelial cells (hRPTEC) from Lifeline Cell Technology to confirm potential miRNA associations with kidney injuries like renal fibrosis in humans.

Urinary miRNA Profiling across CKD Rat Models

Of the 337 miRNAs analyzed, 290 were found to be elevated in obese ZSF1 rats compared to lean controls. With respect to disease progression, 38 miRNAs were altered in obese 14–26-week-old ZSF1 rats. The authors noted a stronger correlation of these miRNAs with age-related disease progression compared to established urinary protein biomarkers such as urinary KIM-1 protein levels. In both rat models, disease progression and kidney damage were confirmed by histopathology, proteinuria, and increased levels of urinary protein biomarkers. PCR-based miRNA profiling of total urine and urinary EVs isolated from obese ZSF1 rats was compared with lean controls and across time points.

To explore whether differences in disease etiologies and renal pathophysiological mechanisms are reflected in the corresponding urinary miRNA patterns, the authors compared urinary miRNA profiles among obese ZSF1 rats and two other CKD models—mRenTG rats and a rat model of glomerulonephritis—where kidney injuries result from different primary mechanisms. Comparatively fewer urinary EV-associated miRNAs were altered in mRenTG rats compared to obese ZSF1 rats, indicating differential biomarker profiles between CKD models with distinct underlying pathophysiologic mechanisms. Notably, decreased miR-138-5p levels in urinary EVs of mRenTG rats were associated with endothelial dysfunction, suggesting its potential as a biomarker for glomerular injury.

Confirming miRNA Associations with Renal Pathology

To confirm a potential association of selected miRNAs in urine of ZSF1 rats with renal fibrosis, experiments were conducted using an in vitro model of renal fibrosis using cultured primary proximal tubule epithelial cells treated with transforming growth factor-beta (TGF-β) or human serum albumin (HSA). TGF-β treatment resulted in increased release of EV-associated miRNAs implicated in TGF-β-mediated renal fibrosis, confirming the link between urinary miRNAs and renal pathology.

Several specific miRNAs, including miR-145-5p, miR-10a-5p, and miR-125b-5p, have demonstrated associations with renal injury and fibrosis in independent studies, suggesting their potential as biomarkers for CKD in both rats and humans. These findings highlight the potential of urinary and urinary EV-associated miRNAs as complementary biomarkers to traditional protein biomarkers, which can provide valuable insights into disease progression to facilitate early detection and improve monitoring and management strategies for CKD patients.

Lifeline Cell Technology Renal & Bladder Cells

Lifeline Cell Technology’s primary kidney cells played a key role in the in vitro studies to supporting the link between urinary miRNAs and renal pathology. They are ideal cell culture models for a wide range of applications from fundamental research to drug screening, to ensure the validity of research findings. Lifeline has a diverse array of renal cell types to further your research:

Read more on our blog to learn how researchers worldwide are utilizing our portfolio of human cells and culture media, to answer their scientific questions.

If you have used our products to power your research, we’d love to feature your work here!

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