Urinary metabolite profiling and risk of progression of diabetic nephropathy in 2670 individuals with type 1 diabetes
Authors:
Stefan Mutter, Erkka Valo, Viljami Aittomäki, Kristian Nybo, Lassi Raivonen, Lena M. Thorn, Carol Forsblom, Niina Sandholm, Peter Würtz, Per-Henrik Groop
This prospective, observational study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in individuals with type 1 diabetes by employing an automated NMR metabolomics technique suitable for large-scale urine sample collections.
Methods
We collected 24-h urine samples for 2670 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy study and measured metabolite concentrations by NMR. Individuals were followed up for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regressions were performed on the entire study population (overall progression), on 1999 individuals with normoalbuminuria and 347 individuals with macroalbuminuria at baseline.
Results
Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage (p < 8 × 10−4): leucine (HR 1.47 [95% CI 1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-Hydroxyisobutyrate was associated with overall progression (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria.
Conclusions/interpretation
Branched-chain amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts.
WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.