Detection of autosomal dominant polycystic kidney disease by NMR spectroscopic fingerprinting of urine

Autosomal dominant polycystic kidney disease (ADPKD) is a frequent cause of kidney failure; however, urinary biomarkers for the disease are lacking. In a step towards identifying such markers, we used multidimensional-multinuclear nuclear magnetic resonance (NMR) spectroscopy with support vector machine-based classification and analyzed urine specimens of 54 patients with ADPKD and slightly reduced estimated glomerular filtration rates. Within this cohort, 35 received medication for arterial hypertension and 19 did not. The results were compared with NMR profiles of 46 healthy volunteers, 10 ADPKD patients on hemodialysis with residual renal function, 16 kidney transplant patients, and 52 type 2 diabetic patients with chronic kidney disease. Based on the average of 51 out of 701 NMR features, we could reliably discriminate ADPKD patients with moderately advanced disease from ADPKD patients with end-stage renal disease, patients with chronic kidney disease of other etiologies, and healthy probands with an accuracy of >80%. Of the 35 patients with ADPKD receiving medication for hypertension, most showed increased excretion of proteins and also methanol. In contrast, elevated urinary methanol was not found in any of the control and other patient groups. Thus, we found that NMR fingerprinting of urine differentiates ADPKD from several other kidney diseases and individuals with normal kidney function. The diagnostic and prognostic potential of these profiles requires further evaluation.