Heckscher, Simon and Ihlo, Nicolas A. and Schueler, Jan and Kellermeier, Fabian and Werner, Jens M. and Nuebel, Barbara and Gross, Verena and May, Matthias and Wullich, Bernd and Kammerl, Martin and Gnewuch, Carsten and Burkhardt, Ralph and Buchholz, Bjoern and Pion, Eric and Aung, Thiha and Banas, Miriam and Schlitt, Hans J. and Oefner, Peter J. and Dettmer, Katja and Gronwald, Wolfram and Behr, Merle and Haerteis, Silke and Schmidt, Katharina M. (2025) Metabolomic profiling of renal cyst fluid in advanced ADPKD: insights from dialysis and transplantation cohorts. METABOLOMICS, 21 (4): 90. ISSN 1573-3882, 1573-3890
Full text not available from this repository. (Request a copy)Abstract
BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder characterized by progressive renal cyst formation, often leading to end-stage kidney disease (ESKD). In contrast to the urinary metabolome in ADPKD, the composition of renal cyst fluid remains largely unexplored.MethodsWe conducted a comprehensive metabolomic analysis of renal cyst fluid from 26 ADPKD patients (20 on dialysis, six with kidney transplants) using H-1-NMR spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Cysts were clustered based on metabolite profiles, and differences were analyzed across groups defined by renal function status (dialysis vs. transplant), cyst volume, and cyst fluid sodium concentrations.ResultsDialysis patients and transplant recipients differed significantly in their renal cyst fluid metabolomes. The former exhibited higher concentrations of myoinositol, creatinine, sucrose, tau-methylhistidine, trigonelline, and sarcosine, while the latter showed increased levels of leucine, isoleucine, valine and alanine. Remarkably, metabolites of the immunosuppressive prodrug mycophenolate mofetil were detected in renal cyst fluids after kidney transplantation. Despite intra- and interindividual variability, cyst fluid from the same patient displayed greater homogeneity. Interestingly, metabolomic profiles were not altered by cyst size.ConclusionThis first systematic metabolomic analysis of renal cyst fluid in advanced ADPKD reveals distinct metabolic signatures linked to renal function status. The data provides novel insights into the pathophysiology of ADPKD and highlight the potentials of renal cyst fluid metabolomics for identifying biomarkers and therapeutic targets.
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