Urinary Biomarkers Link Chronic Kidney Disease to Mitochondrial Dysfunction

An in-depth metabolomic study found that patients with chronic kidney disease (CKD) expressed a group of 13 biomarker metabolites that differentiated them from normal, healthy individuals.

The primary causes of CKD are high blood pressure and diabetes, and rates of both syndromes have risen sharply in the last decade, particularly among people aged 65 and older. The number of Americans with CKD is estimated to be more than 26 million.

Investigators at the University of California, San Diego (USA) and the biomedical company ClinMet (San Diego, CA, USA) collaborated in a study to identify reliable biomarkers in the urine of patients with CKD. The study was carried out using ClinMet's proprietary clinical metabolomics analysis platform.

Gas chromatography-mass spectrometry was used to quantify 94 metabolites in the urine of 193 patients with diabetes mellitus (DM) and CKD (DM+CKD), in patients with DM without CKD (DM–CKD), and in healthy controls. Results revealed that compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts, and 12 of the 13 remained significant when compared with the DM–CKD cohort. Many of the differentially expressed metabolites were water-soluble organic anions.

Analysis of bioinformatics data indicated that 12 of the 13 differentially expressed metabolites were linked to mitochondrial metabolism and suggested the possibility of global suppression of mitochondrial activity in diabetic kidney disease. Supporting this analysis, human diabetic kidney sections were found to express less mitochondrial protein. Urine exosomes from patients with diabetes and CKD had less mitochondrial DNA, and kidney tissues from patients with diabetic kidney disease had lower gene expression of PGC1alpha (a master regulator of mitochondrial synthesis).

"It is clear from this study that urine- and plasma-based metabolomics can be a rich source of biomarkers for understanding and treating diabetic kidney disease and possibly for related cardiovascular complications," said first author Dr. Kumar Sharma, professor of medicine at the University of California, San Diego. "This approach also offers direct insights into biochemical pathways linked to kidney dysfunction. The urine metabolites can indicate the underlying function of the kidney at a biochemical and intracellular level, and are well conserved compared to many cell-based and protein measurements. Urine metabolomics also offers an opportunity to gauge effects of new treatments which will be an advantage to guide precision medicine."

The study was published in the October 10, 2013, online edition of the Journal of the American Society of Nephrology.

Related Links:
University of California, San Diego
ClinMet