1H MR‐based detection of human plasma metabolic alterations in clear cell renal cell carcinoma

Objectives This study aimed to evaluate the potential of plasma‐based proton magnetic resonance spectroscopy (1H‐MRS) for non‐invasive discrimination between clear cell renal cell carcinoma (ccRCC), benign renal masses (angiomyolipoma and oncocytoma) and healthy controls by identifying disease‐specific metabolic signatures. Patients and Methods We performed 1H‐MRS metabolic profiling of human plasma samples from 30 individuals divided into three cohorts: ccRCC ( n = 10, all biopsy‐confirmed, nonmetastatic T3 tumours), benign renal masses ( n = 10, angiomyolipoma or oncocytoma) and healthy controls ( n = 10). Multivariate and univariate statistical analyses were conducted to evaluate group separation and identify differentially abundant metabolites. Metabolite set enrichment analysis was used to identify significantly perturbed metabolic pathways associated with each state. Results We observed altered metabolic plasma profiles in ccRCC patients compared to normal controls and benign patients. We detected significantly increased concentrations of hydroxybutyrate (normal vs. ccRCC, p = 0.008), glucose (normal vs. ccRCC, p = 0.020), (benign vs. ccRCC, p = 0.009), creatinine (normal vs. ccRCC, p = 0.015), (benign vs. ccRCC, p = 0.014) in ccRCC patients' plasma compared to normal controls and benign renal masses plasma. We also found that acetate and myoinositol were significantly elevated in benign (normal vs. benign, p = 0.0002) and ccRCC (normal vs. ccRCC, p = 0.0001) plasma compared to normal controls plasma. Pathway enrichment analysis revealed alterations in fatty acid biosynthesis, amino acid metabolism, nitrogen handling and glycolysis‐related pathways consistent with ccRCC‐associated metabolic reprogramming. Conclusion This pilot study demonstrates that plasma 1H‐MRS can detect metabolic alterations associated with ccRCC and benign renal masses. These findings support the feasibility of using metabolomic profiling as a non‐invasive diagnostic tool for renal mass characterization. Larger validation studies are warranted to confirm diagnostic accuracy and explore utility in clinical decision‐making.