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Contribution of symmetric dimethylarginine to GFR decline in pediatric chronic kidney disease

  • Brooks, Ellen R.1, 2
  • Haymond, Shannon1, 3
  • Rademaker, Alfred1, 4
  • Pierce, Christopher5
  • Helenowski, Irene1, 4
  • Passman, Rod1, 6
  • Vicente, Faye3
  • Warady, Bradley A.7
  • Furth, Susan L.8
  • Langman, Craig B.1, 2
  • 1 Northwestern University, Feinberg School of Medicine, Chicago, IL, USA , Chicago (United States)
  • 2 Ann & Robert H. Lurie Children’s Hospital of Chicago, Division of Kidney Diseases, Mailstop # 37, 225 E. Chicago Ave, Chicago, IL, 60611, USA , Chicago (United States)
  • 3 Ann & Robert H. Lurie Children’s Hospital of Chicago, Department of Pathology, Chicago, IL, USA , Chicago (United States)
  • 4 Feinberg School of Medicine, Division of Biostatistics, Department of Preventive Medicine, Chicago, IL, USA , Chicago (United States)
  • 5 University Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, MD, USA , Baltimore (United States)
  • 6 Northwestern Medical Group, Division of Cardiology, Department of Internal Medicine, Chicago, IL, USA , Chicago (United States)
  • 7 The Children’s Mercy Hospital, Division of Pediatric Nephrology, Kansas City, MO, USA , Kansas City (United States)
  • 8 The Children’s Hospital of Philadelphia, Division of Nephrology, Philadelphia, PA, USA , Philadelphia (United States)
Published Article
Pediatric Nephrology
Publication Date
Dec 07, 2017
DOI: 10.1007/s00467-017-3842-x
Springer Nature


BackgroundIn 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 m2/year) for a period of up to 4 years.MethodsPlasma 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.ResultsFor 352 pCKD subjects, the median [interquartile range] BL mGFR was 45 [35, 57] ml/min/1.73 m2. 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).ConclusionsIn 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.

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