Urinary biomarkers at early ADPKD disease stage

Katja Petzold; Diane Poster; Fabienne Krauer; Katharina Spanaus; Gustav Andreisek; Thi Dan Linh Nguyen-Kim; Ivana Pavik; Thien Anh Ho; Andreas L Serra; Laura Rotar

doi:10.1371/journal.pone.0123555

Urinary biomarkers at early ADPKD disease stage

PLoS One. 2015 Apr 13;10(4):e0123555. doi: 10.1371/journal.pone.0123555. eCollection 2015.

Authors

Affiliations

¹ Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland; EuroCYST Initiative, Coordination Center, University of Zurich, Zurich, Switzerland.
² Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
³ Institute of Clinical Chemistry, University and University Hospital Zurich, Zurich, Switzerland.
⁴ Department of Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, Switzerland.
⁵ Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland.
⁶ Division of Nephrology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain Medical School, Brussels, Belgium.
⁷ Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland; Division of Nephrology, University Hospital Zurich, Zurich, Switzerland; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; EuroCYST Initiative, Coordination Center, University of Zurich, Zurich, Switzerland; Trancyst FP7-PEOPLE-MCA-ITN no. 317246, University of Zurich, Zurich, Switzerland.
⁸ Institute of Physiology and Zurich Center for Integrative Human Physiology, Zurich, Switzerland; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; EuroCYST Initiative, Coordination Center, University of Zurich, Zurich, Switzerland; Trancyst FP7-PEOPLE-MCA-ITN no. 317246, University of Zurich, Zurich, Switzerland.

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course.

Methods: ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results.

Results: In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found.

Conclusion: UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable. Further studies are needed to evaluate the property of the aforementioned biomarkers to assess disease state at early ADPKD stage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers / urine*
Cohort Studies
Demography
Disease Progression
Female
Glomerular Filtration Rate
Humans
Kidney / pathology
Kidney / physiopathology
Male
Models, Biological
Organ Size
Polycystic Kidney, Autosomal Dominant / pathology*
Polycystic Kidney, Autosomal Dominant / physiopathology
Polycystic Kidney, Autosomal Dominant / urine*
Regression Analysis

Substances

Biomarkers

Grants and funding

The study was supported by the EuroCYST Initiative (ERA EDTA), TransCYST (FP7-PEOPLE-MCA-ITN no. 317246), European Community's 7th Framework Program (FP7/2007-2013) under grant n° 305608 (EURenOmics); Action de Recherche Concertée (ARC10/15-029, Communauté Française de Belgique); Inter-University Attraction Pole (IUAP, Belgium Federal Government); the NCCR Kidney. CH program (Swiss National Science Foundation); and the Swiss National Science Foundation 310030-146490.