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Osmolytes in urine may help track CKD progression
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Research published in Nephrology Dialysis Transplantation showed that imbalances in renal osmolyte regulation can lead to increased renal cell damage and more progressive forms of chronic kidney disease. Therefore, researchers determined that increases in these osmolytes found in urine can provide physicians with diagnostic and prognostic data about CKD outcomes.
Researchers noted that biomarkers that are more sensitive in early stage CKD are required to improve diagnosis of the disease, as well as the prognosis of its progression. This need lead to the use of metabolomics to analyze biofluids for metabolic signatures indicating CKD status.
“eGFR can be calculated using the Chronic Kidney Disease Epidemiology Collaboration equation for the Modification of Diet in Renal Disease study equation,” the authors wrote. “However, both measures are relatively insensitive in early stage CKD and their prognostic value is limited.”
Researchers created metabolite profiles for a cohort of 227 patients with eGFRs that ranged from 9.4 mL/min/1.73m2 to 130 mL/min/1.73m2. Independent of baseline eGFR, a subset of 57 patients were investigated for prognostic metabolite markers of CKD progression, according to the study. To validate the efficacy of the metabolomic findings, a transcriptomic analysis of murine models for renal failure was performed.
A linear analysis of the patient data revealed 11 urinary metabolites with statistically significant associations to reduced eGFR. Additionally, it showed urine concentrations of betaine and myo-inositol are significant prognostic markers for CKD progression, according to the study.
“Most significant metabolites decrease in urinary concentration with reduced eGFR and in patients with progressing CKD,” the authors wrote. “However, in these same patients we also observed significant linear increases of myo-inositol and betaine. Both metabolites had the highest absolute [beta] coefficients in our modeling of percent annual eGFR slope and showed prognostic value in predicting patients who rapidly progress from those who remained stable.”
Given the low number of overall samples in the CKD progression analysis, researchers wrote that a larger, multicenter, validation study is warranted. – by Scott Buzby
Disclosures: The research leading to these results has received funding from the European Union’s Seventh Framework Programme FP7/2007-2013 under grant PF7-PEOPLE-2013-ITN-608332. Please see the study for all other authors’ relevant financial disclosures.
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Gil RB, et al. Nephrol Dial Transplant.2018;doi:10.1093/ndt/gfy020.
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