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Identification of a unique urinary biomarker profile in patients with autosomal dominant polycystic kidney disease


Kistler, A D; Mischak, H; Poster, D; Dakna, M; Wüthrich, R P; Serra, A L (2009). Identification of a unique urinary biomarker profile in patients with autosomal dominant polycystic kidney disease. Kidney International, 76(1):89-96.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:July 2009
Deposited On:22 Jun 2009 10:07
Last Modified:05 Apr 2016 13:16
Publisher:Nature Publishing Group
ISSN:0085-2538
Publisher DOI:https://doi.org/10.1038/ki.2009.93
PubMed ID:19340089

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