Abstract
Background
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent etiologies of pediatric chronic kidney disease (CKD). However, no robust mass screening methods have been developed to detect patients with CAKUT, making early intervention to prevent progressive renal failure challenging.
Methods
We applied tandem mass spectrometry (MS/MS) to measure the creatinine (Cr) value from dried blood spot (DBS) analysis, which has been used for newborn mass screening. Subsequently, we evaluated the correlation between DBS Cr measured by MS/MS and serum Cr measured by the conventional method in pediatric patients with CKD. Finally, DBS Cr was measured in 190 full-term, healthy newborns on days 4–6 after birth.
Results
We established a system of MS/MS-based measurement of Cr from DBS. Measured DBS Cr in the pediatric patients showed a strong association with serum Cr (r=0.86; P<0.01). The median DBS Cr value in newborns was 0.222 (interquartile range: 0.189, 0.269) mg/dl. No significant correlations were found between DBS Cr values and body weight, Apgar score, gestational age, and sex in newborns.
Conclusion
We successfully established a method for MS/MS-based measurement of Cr for newborn screening and determined normal reference values for full-term newborns.
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References
Ishikura K, Uemura O, Hamasaki Y et al, Progression to end-stage kidney disease in Japanese children with chronic kidney disease: results of a nationwide prospective cohort study. Nephrol Dial Transplant 2014;29:878–84.
Oh J, Wunsch R, Turzer M et al, Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 2002;106:100–5.
Chadha V, Warady BA . Epidemiology of pediatric chronic kidney disease. Adv Chronic Kidney Dis 2005;12:343–52.
Mitsnefes MM, Laskin BL, Dahhou M, Zhang X, Foster BJ . Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990-2010. JAMA 2013;309:1921–9.
Hadtstein C, Schaefer F . Hypertension in children with chronic kidney disease: pathophysiology and management. Pediatr Nephrol 2008;23:363–71.
Wühl E, Schaefer F . Therapeutic strategies to slow chronic kidney disease progression. Pediatr Nephrol 2008;23:705–16.
Ellis D, Vats A, Moritz ML, Reitz S, Grosso MJ, Janosky JE . Long-term antiproteinuric and renoprotective efficacy and safety of losartan in children with proteinuria. J Pediatr 2003;143:89–97.
Wühl E, Trivelli A, Picca S et al, Strict blood-pressure control and progression of renal failure in children. N Engl J Med 2009;361:1639–50.
Ellis D, Moritz ML, Vats A, Janosky JE . Antihypertensive and renoprotective efficacy and safety of losartan. A long-term study in children with renal disorders. Am J Hypertens 2004;17:928–35.
Soergel M, Verho M, Wühl E, Gellermann J, Teichert L, Schärer K . Effect of ramipril on ambulatory blood pressure and albuminuria in renal hypertension. Pediatr Nephrol 2000;15:113–8.
White CT, Macpherson CF, Hurley RM, Matsell DG . Antiproteinuric effects of enalapril and losartan: a pilot study. Pediatr Nephrol 2003;18:1038–43.
Simonetti GD, von Vigier RO, Konrad M, Rizzi M, Fossali E, Bianchetti MG . Candesartan cilexetil in children with hypertension or proteinuria: preliminary data. Pediatr Nephrol 2006;21:1480–2.
von Vigier RO, Zberg PM, Teuffel O, Bianchetti MG . Preliminary experience with the angiotensin II receptor antagonist irbesartan in chronic kidney disease. Eur J Pediatr 2000;159:590–3.
Yanagihara T, Hamada R, Ishikura K et al, Urinary screening and urinary abnormalities in 3-year-old children in Japan. Pediatr Int 2015;57:354–8.
Sekhar DL, Wang L, Hollenbeak CS, Widome MD, Paul IM . A cost-effectiveness analysis of screening urine dipsticks in well-child care. Pediatrics 2010;125:660–3.
Uemura O, Honda M, Matsuyama T et al, Age, gender, and body length effects on reference serum creatinine levels determined by an enzymatic method in Japanese children: a multicenter study. Clin Exp Nephrol 2011;15:694–9.
Uemura O, Nagai T, Ishikura K et al, Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease. Clin Exp Nephrol 2014;18:626–33.
Boer DP, de Rijke YB, Hop WC, Cransberg K, Dorresteijn EM . Reference values for serum creatinine in children younger than 1 year of age. Pediatr Nephrol 2010;25:2107–13.
Bueva A, Guignard JP . Renal function in preterm neonates. Pediatr Res 1994;36:572–7.
van den Anker JN, de Groot R, Broerse HM et al, Assessment of glomerular filtration rate in preterm infants by serum creatinine: comparison with inulin clearance. Pediatrics 1995;96:1156–8.
Linda L, Ng PD . Validation of Chromatographic Methods. US Food and Drug Administration: Silver Spring, MD, 2014.
Kanda Y . Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013;48:452–8.
Pottel H, Vrydags N, Mahieu B, Vandewynckele E, Croes K, Martens F . Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods. Clin Chim Acta 2008;396:49–55.
Rashed MS . Clinical applications of tandem mass spectrometry: ten years of diagnosis and screening for inherited metabolic diseases. J Chromatogr B Biomed Sci Appl 2001;758:27–48.
den Burger JC, Wilhelm AJ, Chahbouni AC, Vos RM, Sinjewel A, Swart EL . Haematocrit corrected analysis of creatinine in dried blood spots through potassium measurement. Anal Bioanal Chem 2015;407:621–7.
Koop DR, Bleyle LA, Munar M, Cherala G, Al-Uzri A . Analysis of tacrolimus and creatinine from a single dried blood spot using liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2013;926:54–61.
Jopling J, Henry E, Wiedmeier SE, Christensen RD . Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital health care system. Pediatrics 2009;123:e333–7.
Nagasaki K, Minamitani K, Anzo M et al, Guidelines for mass screening of congenital hypothyroidism (2014 revision). Clin Pediatr Endocrinol 2015;24:107–33.
Gary LH, Blas C, Donald HC, Sara C . Newborn Screening by Tandem Mass Spectrometry; Approved Guideline. Clinical and Laboratory Standards Institute: Wayne, PA, 2010.
Schwartz GJ, Feld LG, Langford DJ . A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatr 1984;104:849–54.
Bariciak E, Yasin A, Harrold J, Walker M, Lepage N, Filler G . Preliminary reference intervals for cystatin C and beta-trace protein in preterm and term neonates. Clin Biochem 2011;44:1156–59.
Lim E, Miyamura J, Chen JJ . Racial/ethnic-specific reference intervals for common laboratory tests: a comparison among Asians, Blacks, Hispanics, and White. Hawaii J Med Public Health 2015;74:302–10.
Tabel Y, Haskologlu ZS, Karakas HM, Yakinci C . Ultrasonographic screening of newborns for congenital anomalies of the kidney and the urinary tracts. Urol J 2010;7:161–7.
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STATEMENT OF FINANCIAL SUPPORT
This research was partially supported by Grants-in-Aid for research on efficient screening and health check-ups of infants based on epidemiology from the Japan Agency for Medical Research and Development (AMED). This study was supported by the Japan Agency for Medical Research and Development.
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Nakano, M., Uemura, O., Honda, M. et al. Development of tandem mass spectrometry-based creatinine measurement using dried blood spot for newborn mass screening. Pediatr Res 82, 237–243 (2017). https://doi.org/10.1038/pr.2017.56
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DOI: https://doi.org/10.1038/pr.2017.56
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