Predicting renal disease progression in people with autosomal dominant polycystic kidney disease (ADPKD) is crucial for making a prognosis and for supporting the therapeutic choice of when to start renoprotective medication. Every conventional marker has its limits. A promising method for risk stratification is metabolic profiling. For a study, researchers assessed time-dependent changes in urine metabolites and evaluated prognostic performance to identify patients with a rapidly progressing illness history.

Spot urine samples were analyzed using targeted, quantitative metabolomics (1H NMR-spectroscopy) at baseline (n = 324; 61% female; mean age 45; SD 11; median eGFR 61 mL/min/1.73 m2 ,IQR 42-88; mean years of creatinine follow-up 3.7; SD 1.3) and a sample collected after 3 years of follow-up (n=112). Patients were divided into rapid and slow progressors based on their annualized change of >-3.0 or ≤-3.0 mL/min/1.73 m2/year, respectively, according to their eGFR slope. The important urine metabolites and ratios were chosen after the quantification of 55 urinary metabolites. Using baseline urine samples, prognostic performance in identifying patients with a rapidly progressive course was evaluated using logistic regression. To determine if changes in urine metabolites throughout a 3-year follow-up period varied between rapid and slow progressors, repeated-measures ANOVA was employed.

The predictive performance of urine metabolites in a single urinary sample was equivalent to a model that included height-adjusted total kidney volume (htTKV, AUC=0.67). The predictive power of the metabolite model was enhanced when combined with htTKV (AUC=0.75). In keeping with an overall rise in the myoinositol/citrate ratio as GFR drops, the longitudinal analysis revealed an increase in the myoinositol/citrate ratio (P<0.001) in rapid progressors but no significant change in those with slow progression.

In ADPKD, a metabolic profile evaluated at a single time point performed at least as well in terms of prognosis as an imaging-based risk factor. Over a 3-year follow-up period, changes in urine metabolites were linked to a rapidly advancing illness course.