Cargando…

Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic diseases, is characterized by the presence of numerous fluid-filled renal cysts and is a leading cause of end-stage renal disease (ESRD). Urinary biomarkers may be useful for predicting the varia...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Hyunsuk, Sung, Jinmo, Bae, Ju Young, Lee, Poongyeon, Oh, Yun Kyu, Kim, Hyunho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Nephrology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731784/
https://www.ncbi.nlm.nih.gov/pubmed/35791741
http://dx.doi.org/10.23876/j.krcp.21.303
_version_ 1784845977887178752
author Kim, Hyunsuk
Sung, Jinmo
Bae, Ju Young
Lee, Poongyeon
Oh, Yun Kyu
Kim, Hyunho
author_facet Kim, Hyunsuk
Sung, Jinmo
Bae, Ju Young
Lee, Poongyeon
Oh, Yun Kyu
Kim, Hyunho
author_sort Kim, Hyunsuk
collection PubMed
description BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic diseases, is characterized by the presence of numerous fluid-filled renal cysts and is a leading cause of end-stage renal disease (ESRD). Urinary biomarkers may be useful for predicting the variable course of ADPKD progression from cyst growth to ESRD. METHODS: To identify candidate urinary biomarkers of ADPKD progression, we used CRISPR/Cas9 genome editing to generate porcine fibroblasts with mono- and biallelic ADPKD gene knockout (PKD2(+/–) and PKD2(–/–), respectively). We then performed RNA-sequencing analysis on these cells. RESULTS: Levels of osteopontin (OPN), which is expressed by renal epithelial tubular cells and excreted into urine, were reduced in PKD2(–/–) cells but not in PKD2(+/–) cells. OPN levels were also reduced in the renal cyst cells of ADPKD patients. Next, we investigated whether OPN excretion was decreased in patients with ADPKD via enzyme-linked immunosorbent assay. OPN levels excreted into renal cyst cell culture media and urine from ADPKD patients were decreased. To investigate whether OPN can predict the rate of ADPKD progression, we compared urinary excretion of OPN in ADPKD patients with slow progression and those with rapid progression. Those with rapid progression had an estimated glomerular filtration rate of >60 mL/min/1.73 m(2). Urinary OPN excretion levels were lower in rapid progressors than in slow progressors. CONCLUSION: These findings suggest that OPN is a useful urinary biomarker for predicting ADPKD progression.
format Online
Article
Text
id pubmed-9731784
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher The Korean Society of Nephrology
record_format MEDLINE/PubMed
spelling pubmed-97317842022-12-16 Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression Kim, Hyunsuk Sung, Jinmo Bae, Ju Young Lee, Poongyeon Oh, Yun Kyu Kim, Hyunho Kidney Res Clin Pract Original Article BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), one of the most common human monogenic diseases, is characterized by the presence of numerous fluid-filled renal cysts and is a leading cause of end-stage renal disease (ESRD). Urinary biomarkers may be useful for predicting the variable course of ADPKD progression from cyst growth to ESRD. METHODS: To identify candidate urinary biomarkers of ADPKD progression, we used CRISPR/Cas9 genome editing to generate porcine fibroblasts with mono- and biallelic ADPKD gene knockout (PKD2(+/–) and PKD2(–/–), respectively). We then performed RNA-sequencing analysis on these cells. RESULTS: Levels of osteopontin (OPN), which is expressed by renal epithelial tubular cells and excreted into urine, were reduced in PKD2(–/–) cells but not in PKD2(+/–) cells. OPN levels were also reduced in the renal cyst cells of ADPKD patients. Next, we investigated whether OPN excretion was decreased in patients with ADPKD via enzyme-linked immunosorbent assay. OPN levels excreted into renal cyst cell culture media and urine from ADPKD patients were decreased. To investigate whether OPN can predict the rate of ADPKD progression, we compared urinary excretion of OPN in ADPKD patients with slow progression and those with rapid progression. Those with rapid progression had an estimated glomerular filtration rate of >60 mL/min/1.73 m(2). Urinary OPN excretion levels were lower in rapid progressors than in slow progressors. CONCLUSION: These findings suggest that OPN is a useful urinary biomarker for predicting ADPKD progression. The Korean Society of Nephrology 2022-11 2022-06-20 /pmc/articles/PMC9731784/ /pubmed/35791741 http://dx.doi.org/10.23876/j.krcp.21.303 Text en Copyright © 2022 The Korean Society of Nephrology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial and No Derivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ) which permits unrestricted non-commercial use, distribution of the material without any modifications, and reproduction in any medium, provided the original works properly cited.
spellingShingle Original Article
Kim, Hyunsuk
Sung, Jinmo
Bae, Ju Young
Lee, Poongyeon
Oh, Yun Kyu
Kim, Hyunho
Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression
title Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression
title_full Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression
title_fullStr Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression
title_full_unstemmed Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression
title_short Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression
title_sort identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9731784/
https://www.ncbi.nlm.nih.gov/pubmed/35791741
http://dx.doi.org/10.23876/j.krcp.21.303
work_keys_str_mv AT kimhyunsuk identificationofosteopontinasaurinarybiomarkerforautosomaldominantpolycystickidneydiseaseprogression
AT sungjinmo identificationofosteopontinasaurinarybiomarkerforautosomaldominantpolycystickidneydiseaseprogression
AT baejuyoung identificationofosteopontinasaurinarybiomarkerforautosomaldominantpolycystickidneydiseaseprogression
AT leepoongyeon identificationofosteopontinasaurinarybiomarkerforautosomaldominantpolycystickidneydiseaseprogression
AT ohyunkyu identificationofosteopontinasaurinarybiomarkerforautosomaldominantpolycystickidneydiseaseprogression
AT kimhyunho identificationofosteopontinasaurinarybiomarkerforautosomaldominantpolycystickidneydiseaseprogression