Supplementary Material for: Change in Urinary Myoinositol/Citrate Ratio Associates with Progressive Loss of Renal Function in ADPKD Patients

<b><i>Introduction:</i></b> In autosomal dominant polycystic kidney disease (ADPKD) patients, predicting renal disease progression is important to make a prognosis and to support the clinical decision whether to initiate renoprotective therapy. Conventional markers all have their limitations. Metabolic profiling is a promising strategy for risk stratification. We determined the prognostic performance to identify patients with a fast progressive disease course and evaluated time-dependent changes in urinary metabolites. <b><i>Methods:</i></b> Targeted, quantitative metabolomics analysis (¹H NMR-spectroscopy) was performed on spot urinary samples at two time points, baseline (<i>n</i> = 324, 61% female; mean age 45 years, 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 obtained after 3 years of follow-up (<i>n</i> = 112). Patients were stratified by their eGFR slope into fast and slow progressors based on an annualized change of &gt; −3.0 or ≤ −3.0 mL/min/1.73 m²/year, respectively. Fifty-five urinary metabolites and ratios were quantified, and the significant ones were selected. Logistic regression was used to determine prognostic performance in identifying those with a fast progressive course using baseline urine samples. Repeated-measures ANOVA was used to analyze whether changes in urinary metabolites over a 3-year follow-up period differed between fast and slow progressors. <b><i>Results:</i></b> In a single urinary sample, the prognostic performance of urinary metabolites was comparable to that of a model including height-adjusted total kidney volume (htTKV, AUC = 0.67). Combined with htTKV, the predictive value of the metabolite model increased (AUC = 0.75). Longitudinal analyses showed an increase in the myoinositol/citrate ratio (<i>p</i> &lt; 0.001) in fast progressors, while no significant change was found in those with slow progression, which is in-line with an overall increase in the myoinositol/citrate ratio as GFR declines. <b><i>Conclusion:</i></b> A metabolic profile, measured at a single time point, showed at least equivalent prognostic performance to an imaging-based risk marker in ADPKD. Changes in urinary metabolites over a 3-year follow-up period were associated with a fast progressive disease course.