@article{ad2c27a7714b4f35b98a2d80ea66bdae,
title = "Contribution of symmetric dimethylarginine to GFR decline in pediatric chronic kidney disease",
abstract = " Background: In pediatric chronic kidney disease (pCKD), traditional factors (proteinuria, etiology, and race) do not fully explain disease progression. The levels of methylated arginine derivatives (MADs: asymmetric and symmetric dimethylarginine, respectively) rise in CKD and increase with CKD progression. The impact of MADs on glomerular filtration rate (GFR) decline has not been examined in pCKD. The aim of this study was to examine the additive impact of baseline (BL) levels of MADs on directly measured GFR (mGFR) decline per year (ml/min/1.73 m 2 /year) for a period of up to 4 years. Methods: Plasma and data, including mGFR by plasma iohexol clearance, were provided by the prospective, observational Chronic Kidney Disease in Children study. BL MADs were analyzed by high-performance liquid chromatography–tandem mass spectrometry. Results: For 352 pCKD subjects, the median [interquartile range] BL mGFR was 45 [35, 57] ml/min/1.73 m 2 . The levels of BL MADs were inversely related to the initial mGFR and its decline over time (p < 0.0005) but not to the rate of decline. Covariates, non-glomerulopathy and Tanner stage of ≥ 3 demonstrated weaker relationships between BL levels and beginning mGFR (p = 0.004 and p = 0.002, respectively). Conclusions: In pCKD, higher concentrations of BL MADs were inversely related to BL mGFR. MADs did not affect the CKD progression rate. Quantification of this relationship is novel to the pCKD literature.",
keywords = "CKD progression, Chronic kidney disease, Methylated arginine derivatives, Pediatric, SDMA",
author = "Brooks, {Ellen R.} and Shannon Haymond and Alfred Rademaker and Christopher Pierce and Irene Helenowski and Rod Passman and Faye Vicente and Warady, {Bradley A.} and Furth, {Susan L.} and Langman, {Craig B.}",
note = "Funding Information: This work was supported by Award R01HD074596 in response to PAR 11-322, “Biomarkers: Bridging Pediatric and Adult Therapeutics” from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Data and specimens were provided by the Principal Investigators, Susan L. Furth, MD, PhD and Bradley A. Warady, MD, and the Steering Committee of The Chronic Kidney Disease in Children Study (CKiD), Award UO1 DK066174 from the National Institute for Diabetes, Digestive, and Kidney Diseases. Our thanks to the CKiD Steering Committee and Data Coordinating Center (Johns Hopkins University, Baltimore, MD) staff, including: Matthew Matheson, Dr. Allison Abraham, Judith Jerry Fluker, and Kelly McDermott for identifying and coordinating the release of data and specimens that made this study possible. All aspects of this investigation were carried out using standards of professional and ethical conduct of human research in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. This included maintaining the confidentiality of de-identified data and specimens. This investigation was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Award R01HD074596 and was approved by the Institutional Review Board of the Ann & Robert H. Lurie Children{\textquoteright}s Hospital (Lurie Children{\textquoteright}s) of Chicago, Illinois. pCKD patients originally provided consent and were enrolled into the CKiD study at 55 IRB approved study sites across North America, which included consent for specimen archival and use of specimens for future unknown research. Funding Information: Acknowledgements This work was supported by Award R01HD074596 in response to PAR 11-322, BBiomarkers: Bridging Pediatric and Adult Therapeutics^ from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Data and specimens were provided by the Principal Investigators, Susan L. Furth, MD, PhD and Bradley A. Warady, MD, and the Steering Committee of The Chronic Kidney Disease in Children Study (CKiD), Award UO1 DK066174 from the National Institute for Diabetes, Digestive, and Kidney Diseases. Publisher Copyright: {\textcopyright} 2017, IPNA.",
year = "2018",
month = apr,
day = "1",
doi = "10.1007/s00467-017-3842-x",
language = "English (US)",
volume = "33",
pages = "697--704",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",
number = "4",
}