Aadil Kakajiwala1,2, Thomas O Jemielita3, Lawrence Copelovitch4,5, Mary B Leonard6, Susan L Furth4,3,5, Amy York4, Maryjane Benton4, Andrew N Hoofnagle7, Kimberly Windt4, Karen Merrigan4, April Lederman4, Michelle R Denburg4,3,5,8. 1. Department of Pediatrics, Division of Nephrology, Washington University in St. Louis School of Medicine, 660 Euclid Ave, Campus Box 8116, St. Louis, MO, 63110, USA. akakajiwala@wustl.edu. 2. Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. akakajiwala@wustl.edu. 3. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 4. Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. 5. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 6. Stanford University School of Medicine, Stanford, CA, USA. 7. University of Washington School of Medicine, Seattle, WA, USA. 8. Center for Pediatric Clinical Effectiveness, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Abstract
BACKGROUND: Variability in measures of mineral metabolism has not been studied in pediatric end stage kidney disease. We sought to determine the intra-individual variability in measures of mineral metabolism in children on hemodialysis (HD) and its impact on clinical decision-making. METHODS: We conducted a prospective single-center study of children (3.6-17.3 years old) on chronic HD. Serial twice weekly measures of serum calcium, phosphate and intact parathyroid hormone (PTH), as well as weekly measures of fibroblast growth factor 23 (FGF23) and vitamin D metabolites, were obtained over a 12-week period in 10 children. Samples (n = 226) were assayed in a single batch at the end of the study. RESULTS: The median intra-individual coefficient of variation (CV) calculated by 4-week blocks was 5.1-6.5% for calcium, 9.5-14.9% for phosphate and 32.7-33.4% for PTH. The median overall CV for FGF23 was 44.4%. Using the first value of each block as a reference, subsequent values would dictate a discrepant management decision 33-56%, 19-28%, and 30-33% of the time for calcium, phosphate, and PTH, respectively. Adjusting for sex and age, most of the variability in phosphate and PTH was attributable to within-participant variability. For calcium, 49% of the variability was attributable to day of blood collection (Monday vs. Friday). The median (range) of an individual participant's values within clinical target ranges was 55% (26-86%) for calcium, 58% (0-96%) for phosphate, and 21% (0-64%) for PTH. CONCLUSIONS: There is considerable intra-individual variability in measures of mineral metabolism that serve as surrogate markers for bone health in children on HD. Within a 4-week period, at least 20-30% of measures would dictate a discrepant decision from the referent measure of that month. These findings have important implications for clinical decision-making and underscore the need to base therapeutic decisions on trends rather than single measurements.
BACKGROUND: Variability in measures of mineral metabolism has not been studied in pediatric end stage kidney disease. We sought to determine the intra-individual variability in measures of mineral metabolism in children on hemodialysis (HD) and its impact on clinical decision-making. METHODS: We conducted a prospective single-center study of children (3.6-17.3 years old) on chronic HD. Serial twice weekly measures of serum calcium, phosphate and intact parathyroid hormone (PTH), as well as weekly measures of fibroblast growth factor 23 (FGF23) and vitamin D metabolites, were obtained over a 12-week period in 10 children. Samples (n = 226) were assayed in a single batch at the end of the study. RESULTS: The median intra-individual coefficient of variation (CV) calculated by 4-week blocks was 5.1-6.5% for calcium, 9.5-14.9% for phosphate and 32.7-33.4% for PTH. The median overall CV for FGF23 was 44.4%. Using the first value of each block as a reference, subsequent values would dictate a discrepant management decision 33-56%, 19-28%, and 30-33% of the time for calcium, phosphate, and PTH, respectively. Adjusting for sex and age, most of the variability in phosphate and PTH was attributable to within-participant variability. For calcium, 49% of the variability was attributable to day of blood collection (Monday vs. Friday). The median (range) of an individual participant's values within clinical target ranges was 55% (26-86%) for calcium, 58% (0-96%) for phosphate, and 21% (0-64%) for PTH. CONCLUSIONS: There is considerable intra-individual variability in measures of mineral metabolism that serve as surrogate markers for bone health in children on HD. Within a 4-week period, at least 20-30% of measures would dictate a discrepant decision from the referent measure of that month. These findings have important implications for clinical decision-making and underscore the need to base therapeutic decisions on trends rather than single measurements.
Entities:
Keywords:
End stage kidney disease; Fibroblast growth factor 23; Hemodialysis; Metabolic bone disease; Parathyroid hormone; Pediatrics; Variability
Authors: Tamara Isakova; Huiliang Xie; Wei Yang; Dawei Xie; Amanda Hyre Anderson; Julia Scialla; Patricia Wahl; Orlando M Gutiérrez; Susan Steigerwalt; Jiang He; Stanley Schwartz; Joan Lo; Akinlolu Ojo; James Sondheimer; Chi-yuan Hsu; James Lash; Mary Leonard; John W Kusek; Harold I Feldman; Myles Wolf Journal: JAMA Date: 2011-06-15 Impact factor: 56.272
Authors: Antonio Alberto Lopes; Lin Tong; Jyothi Thumma; Yun Li; Douglas S Fuller; Hal Morgenstern; Jürgen Bommer; Peter G Kerr; Francesca Tentori; Takashi Akiba; Brenda W Gillespie; Bruce M Robinson; Friedrich K Port; Ronald L Pisoni Journal: Am J Kidney Dis Date: 2012-03-03 Impact factor: 8.860
Authors: Katherine Wesseling-Perry; Renata C Pereira; Chi-Hong Tseng; Robert Elashoff; Joshua J Zaritsky; Ora Yadin; Shobha Sahney; Barbara Gales; Harald Jüppner; Isidro B Salusky Journal: Clin J Am Soc Nephrol Date: 2011-11-03 Impact factor: 8.237
Authors: Clare Gardham; Paul E Stevens; Michael P Delaney; Marica LeRoux; Adrian Coleman; Edmund J Lamb Journal: Clin J Am Soc Nephrol Date: 2010-05-24 Impact factor: 8.237
Authors: Myles Wolf; Miklos Z Molnar; Ansel P Amaral; Maria E Czira; Anna Rudas; Akos Ujszaszi; Istvan Kiss; Laszlo Rosivall; Janos Kosa; Peter Lakatos; Csaba P Kovesdy; Istvan Mucsi Journal: J Am Soc Nephrol Date: 2011-03-24 Impact factor: 10.121
Authors: Jennifer E Flythe; Jula K Inrig; Tariq Shafi; Tara I Chang; Kathryn Cape; Kumar Dinesh; Shrikanth Kunaparaju; Steven M Brunelli Journal: Am J Kidney Dis Date: 2013-03-06 Impact factor: 8.860
Authors: Thomas J Laha; Frederick G Strathmann; Zhican Wang; Ian H de Boer; Kenneth E Thummel; Andrew N Hoofnagle Journal: Clin Chem Date: 2012-09-11 Impact factor: 8.327