Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease

Progressive disruption of renal tubular integrity in the setting of increased cellular proliferation and apoptosis is a feature of ADPKD. Here we evaluated the effect of these processes on the expression of NGAL and IL-18, markers of tubular injury, in rodent models and in the cyst fluid and urine o...

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Main Authors:	Parikh, Chirag R., Dahl, Neera K., Chapman, Arlene, Bost, James E., Edelstein, Charles L., Comer, Diane M., Zeltner, Raoul, Tian, Xin, Grantham, Jared J., Somlo, Stefan
Format:	Online
Language:	English
Published:	2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319327/

id	pubmed-3319327
recordtype	oai_dc
spelling	pubmed-33193272012-10-01 Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease Parikh, Chirag R. Dahl, Neera K. Chapman, Arlene Bost, James E. Edelstein, Charles L. Comer, Diane M. Zeltner, Raoul Tian, Xin Grantham, Jared J. Somlo, Stefan Article Progressive disruption of renal tubular integrity in the setting of increased cellular proliferation and apoptosis is a feature of ADPKD. Here we evaluated the effect of these processes on the expression of NGAL and IL-18, markers of tubular injury, in rodent models and in the cyst fluid and urine of patients with ADPKD. Two mouse models where Pkd2 was inactivated which resulted in early or adult onset cysts, were used to evaluate NGAL levels. Further, the Han:SPRD rat model of polycystic disease was used to study IL-18 levels. In four annual serial urine samples from 107 patients with ADPKD in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) study, NGAL and IL-18 excretion rates were determined in conjunction with measures of total kidney volume and estimated GFR (eGFR) by the MDRD equation. Kidneys from affected mice and rats showed prominent expression of NGAL and IL-18/IL-18R, respectively, in epithelial cells lining kidney cysts. In human ADPKD cyst fluid, both NGAL and IL-18 were elevated. In CRISP patients, the mean percentage increase in total kidney volume was 5.4 /year and the mean decline in eGFR 2.4 mL/min/year. The trend of increased mean urine NGAL and IL-18 over three years was statistically significant; however, there was no association of tertiles of IL-18 or quartiles of NGAL and the change in total kidney volume or eGFR over this period. Thus, urinary NGAL and IL-18 excretion are mildly and stably elevated in ADPKD, but do not correlate with changes in total kidney volume or kidney function. This may be due, in part, to the lack of communication between individual cysts and the urinary collecting system in this disorder. 2012-01-18 2012-04 /pmc/articles/PMC3319327/ /pubmed/22258321 http://dx.doi.org/10.1038/ki.2011.465 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Parikh, Chirag R. Dahl, Neera K. Chapman, Arlene Bost, James E. Edelstein, Charles L. Comer, Diane M. Zeltner, Raoul Tian, Xin Grantham, Jared J. Somlo, Stefan
spellingShingle	Parikh, Chirag R. Dahl, Neera K. Chapman, Arlene Bost, James E. Edelstein, Charles L. Comer, Diane M. Zeltner, Raoul Tian, Xin Grantham, Jared J. Somlo, Stefan Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease
author_facet	Parikh, Chirag R. Dahl, Neera K. Chapman, Arlene Bost, James E. Edelstein, Charles L. Comer, Diane M. Zeltner, Raoul Tian, Xin Grantham, Jared J. Somlo, Stefan
author_sort	Parikh, Chirag R.
title	Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease
title_short	Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease
title_full	Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease
title_fullStr	Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease
title_full_unstemmed	Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease
title_sort	evaluation of urine biomarkers of kidney injury in polycystic kidney disease
description	Progressive disruption of renal tubular integrity in the setting of increased cellular proliferation and apoptosis is a feature of ADPKD. Here we evaluated the effect of these processes on the expression of NGAL and IL-18, markers of tubular injury, in rodent models and in the cyst fluid and urine of patients with ADPKD. Two mouse models where Pkd2 was inactivated which resulted in early or adult onset cysts, were used to evaluate NGAL levels. Further, the Han:SPRD rat model of polycystic disease was used to study IL-18 levels. In four annual serial urine samples from 107 patients with ADPKD in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) study, NGAL and IL-18 excretion rates were determined in conjunction with measures of total kidney volume and estimated GFR (eGFR) by the MDRD equation. Kidneys from affected mice and rats showed prominent expression of NGAL and IL-18/IL-18R, respectively, in epithelial cells lining kidney cysts. In human ADPKD cyst fluid, both NGAL and IL-18 were elevated. In CRISP patients, the mean percentage increase in total kidney volume was 5.4 /year and the mean decline in eGFR 2.4 mL/min/year. The trend of increased mean urine NGAL and IL-18 over three years was statistically significant; however, there was no association of tertiles of IL-18 or quartiles of NGAL and the change in total kidney volume or eGFR over this period. Thus, urinary NGAL and IL-18 excretion are mildly and stably elevated in ADPKD, but do not correlate with changes in total kidney volume or kidney function. This may be due, in part, to the lack of communication between individual cysts and the urinary collecting system in this disorder.
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319327/
_version_	1611518910967840768

Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease

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