Identification of a unique urinary biomarker profile in patients with autosomal dominant polycystic kidney disease.
To gain some insight into early disease progression in human autosomal dominant polycystic kidney disease (ADPKD), we analyzed the urine proteome of 41 young patients with ADPKD whose renal function was relatively preserved. Using capillary electrophoresis and mass spectrometry, we compared these results to those from age-matched healthy controls and patients with other renal diseases. There were 197 proteins with significantly altered urinary excretion; and 38 of them could be sequenced, most of which were collagen fragments. This suggests that there is high turnover of extracellular matrix proteins. Uromodulin peptides, previously implicated in tubular injury, were also found in the urine specimens. These marker proteins were found to distinguish patients from controls with a high degree of accuracy. The sensitivity and specificity of this marker set remained high in an independent validation cohort of 24 patients with ADPKD and 35 healthy controls, and even in comparisons of patients with a variety of other renal diseases or patients with kidney or bladder cancer. These findings present a potential hypothesis for the mechanisms of disease progression in ADPKD which will need to be confirmed by further studies.
Kistler
Andreas D
AD
Department of Nephrology, University Hospital, Zürich, Switzerland. andreas.kistler@usz.ch
Mischak
Harald
H
Poster
Diane
D
Dakna
Mohammed
M
Wüthrich
Rudolf P
RP
Serra
Andreas L
AL