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Elevated Creatinine: But Is It Renal Failure? Molly Wong Vega, MS, RD,a,b Sarah J. Swartz, MD,a,b Sridevi Devaraj, PhD, DABCC, FRSC,a,c Srivaths Poyyapakkam, MD,MSa,b

Serum creatinine is typically used to evaluate function. Yet, it is abstract a marker that can only provide estimations of kidney function because it can be influenced by other factors, such as dietary intake. The expanding field of infant formula selection in recent history has given many options for parents who are unable to provide breastmilk. Standard infant formulas and breastmilk generally fall within a select range of content. With greater accessibility to internet-based medical advice (licensed or unlicensed), parents and families have more chances to be exposed to opportunistic websites and opinions that may provide harmful information. In this report, we describe the case of excessive dietary creatine intake in an infant who presented with elevated creatinine while otherwise appearing healthy and having normal . After in-depth evaluation of nutritional intake, there was a suspicion for high creatine load of the infant’s homemade formula, which was composed of beef liver and various unregulated nutritional powders. Within 12 hours of stopping the infant’s homemade formula and providing intravenous fluids, the infant’s creatinine normalized. aTexas Children’s Hospital, Houston, Texas; and bSection of We highlight the importance of in-depth nutrition assessments and education , cDepartments of Pediatrics and Pathology and on the health risks associated with improper formula selection. Immunology, Baylor College of Medicine, Houston, Texas Ms Wong Vega and Drs Swartz, Devaraj, and Srivaths drafted the initial manuscript and reviewed and revised the manuscript; and all authors approved fi Serum creatinine is used as a marker to Creatine is also essential for the nal manuscripts submitted and agree to be accountable for all aspects of the work. evaluate kidney function and estimate maintaining energy levels necessary for DOI: glomerular filtration rate because of its brain development and is important for https://doi.org/10.1542/peds.2019-2828 complete filtration by the kidney.1,2 neural development.4 Accepted for publication Dec 16, 2019 However, there are disadvantages to spontaneously cyclize to form creatine Address correspondence to Molly Wong Vega, MS, using creatinine as an indicator of and then breaks down to creatinine. RD, Texas Children’s Hospital, Renal and kidney function. Serum creatinine Creatine is synthesized from , Pheresis, 1102 Bates St, Suite 245, Houston, TX 77030. E-mail: [email protected] levels can be influenced by age, sex, , and S-adenosyl muscle mass, diet, and chronic illness.3 primarily in the liver.5 It has been PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Advancements have made the use of estimated that the infant requirement cystatin C available as a in for creatine is ∼4.26 mmol per week Copyright © 2020 by the American Academy of Pediatrics the assessment of glomerular filtration (80 mg per day), taking into account FINANCIAL DISCLOSURE: rate. The uses of cystatin C if available growth and creatine loss.6 De novo The authors have indicated ∼ they have no financial relationships relevant to this are supported by the literature because synthesis accounts for 90% of article to disclose. it appears to follow maturational creatine accretion in infants receiving FUNDING: No external funding. changes in glomerular filtration rate human milk, with potential decreases in POTENTIAL CONFLICT OF INTEREST: more closely.3 endogenous production in formula-fed The authors have indicated they have no potential conflicts of interest infants given higher creatine contents. Creatinine is formed from creatine. to disclose. Muscle contains the most significant In this article, we present the case of stores of creatine and creatine a 4-month-old boy with elevated To cite: Wong Vega M, Swartz SJ, Devaraj S, phosphate, where they play a critical creatinine without previous history of et al. Elevated Serum Creatinine: But Is It Renal Failure?. Pediatrics. 2020;146(1):e20192828 role in cellular energy . renal impairment receiving

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 1, July 2020:e20192828 CASE REPORT a homemade infant formula, which On examination, the patient was case presentation. First, this illustrates the need to critically a well-nourished infant with a weight homemade baby formula included the evaluate this biomarker. of 6.8 kg (40th percentile; Z score use of beef liver. Beef contains the 20.26), length was 57.2 cm (less than largest percentage of naturally the third percentile; Z score 23.21), occurring dietary creatine. Estimated CASE REPORT and head circumference was maximal creatine content of this A 4-month-old boy, born at 31 weeks 40.5 cm (17th percentile; Z score homemade formula was 197 mg per (corrected gestational age 8 weeks) 20.95). Corrected gestational age 1 L recipe or ∼1500 mmol/L.6 For with a 5-week NICU stay, with anthropometrics were weight: reference, Edison et al9 reported gastroesophageal reflux, presented to 1.825 (96th percentile), head creatine concentrations of human the hospital emergency department circumference: 1.33 (91st percentile), milk (70 mmol/L) and other common for evaluation of elevated serum and length: 20.43 (33rd percentile). formulas ranging from 10 to creatinine. He was seen by his He was sleepy but arousable, with 334 mmol/L. Recommendations on pediatrician for his 4-month well- a normal blood pressure, moist the avoidance of cow’s milk as child visit, where his parents mucous membranes, and an a primary source of nutrition for informed his physician that they had otherwise unremarkable physical infants have been centered on started him on a custom formula examination. In addition to elevated development of and its high named Weston Price Beef Liver creatinine, laboratory evaluation renal solute load.10 The creatine Formula.7 This formula consists of revealed mildly elevated serum content of cow’s milk has been 3 3/4 cup chicken broth, 2 oz beef potassium of 6 mEq/L and mildly reported at 550 mmol/L, meaning this liver, 5 tablespoons lactose (brand elevated phosphorus of 8 mg/dL; the homemade formula could have been NOW), 1/4 teaspoon Bifidobacterium remainder of his and ∼3 times higher than the creatine infantis, 1/4 cup homemade liquid blood counts were normal. content of cow’s milk.6 whey, 1 tablespoon coconut oil, 1/2 Additionally, a renal ultrasound Second, this homemade baby formula teaspoon cod liver oil, 1 teaspoon revealed both kidneys to be normal was made up of many powders and sunflower oil, 2 teaspoons olive oil, in appearance. nutritional supplements, thereby and 1/4 teaspoon acerola powder The infant’s custom formula was allowing for the potential of creatine (brand NOW).7 The mother discontinued, and he was started on contamination of any one of these introduced this custom formula intravenous maintenance fluids. His products. In the United States, the without the pediatrician’s knowledge repeat laboratory tests 12 hours after dietary supplement industry is because of concerns related to starting intravenous fluid showed regulated by the Food and Drug previous formula intolerance. The improvement in creatinine to Administration, under the provisions infant had been tried on multiple 0.32 mg/dL (28 mmol/L) and blood of the Dietary Supplement Health and other formulas in conjunction with nitrogen of 8 mg/dL. Serum Education Act of 1994. Unlike food his pediatrician because of worsening potassium and phosphorus stuffs, supplements do not need to be of reflux, constipation, increased normalized at 4.1 mEq/L and 5.5 evaluated for efficacy or purity. Many fussiness, and nasal congestion. mg/dL. Serum cystatin C sent at the reports exist on contamination of The only other formula that was same time as creatinine from both dietary supplements on national and somewhat agreeable was Alimentum the previous day and next morning international scale.11,12 Weston (ready to feed) because it only caused sample was normal at 0.8 mg/L. Price’s Web site gives brand constipation. He had been tolerating recommendations, of which none the custom formula with no such were third party tested at the time of issues. Because of concern for DISCUSSION the patient’s emergency center visit.4 possible hyponatremia, laboratories Obtaining a cystatin C level was were checked, which showed a serum Creatine has been identified as an instrumental in confirming our creatinine 1.29 mg/dL (114 mmol/L) ergogenic and medical aide that does hypothesis: intake of a homemade with repeat creatinine 1.61 mg/dL not lead to in adults baby formula led to increases in (142 mmol/L). The age-based normal with normal kidney function.13 It is serum creatinine for this patient. We value of creatinine for this patient is unknown how higher levels of postulate that this patient’s transient ∼0.15 to 0.3 mg/dL (15–30 mmol/L). creatine intake over time would have rise in serum creatinine was due to He was seen emergently at this influenced this infant’s kidney inadvertent high dietary creatine hospital for a recheck, which showed function long term, but given the intake.8 continued increase in creatinine to patient’s elevated potassium and 2.09 mg/dL (185 mmol/L) and with High creatine intake could have been phosphorus alterations, metabolic a of 13 mg/dL. achieved by 2 primary sources in this control was clearly affected, which

Downloaded from www.aappublications.org/news by guest on October 1, 2021 2 WONG VEGA et al could have led to life threatening further evaluation and consideration Available at: https://www.westonaprice. cardiac arrhythmias. Additionally, for dialysis verses simply changing org/health-topics/childrens-health/ the higher renal solute load formula. Additionally, it demonstrates formula-homemade-baby-formula/. could have had similar consequences the potential risks in providing Accessed May 21, 2019 related to consumption of high formulas not regulated by 8. Kalhan SC, Gruca L, Marczewski S, renal solute load milks with pharmaceutical level manufacturing Bennett C, Kummitha C. Whole the potential for developing standards and how we can better body creatine and protein kinetics dehydration. educate parents on the risks of in healthy men and women: improper formula selection. effects of creatine and Serum creatinine, though the most supplementation. Amino Acids. 2016; common biomarker of renal function, 48(3):677–687 REFERENCES has some limitations pertaining to the 9. Edison EE, Brosnan ME, Aziz K, Brosnan method of measurement as well as 1. Staples A, LeBlond R, Watkins S, Wong C, JT. Creatine and guanidinoacetate some inherent properties. Jaffe’s Brandt J. Validation of the revised content of human milk and infant method of measuring serum Schwartz estimating equation in formulas: implications for creatine creatinine would also measure a predominantly non-CKD population. deficiency syndromes and amino acid noncreatinine chromogens (including Pediatr Nephrol. 2010;25(11):2321–2326 metabolism. Br J Nutr. 2013;110(6): – glucose, vitamin C, proteins, acetone 2. Schwartz GJ, Work DF. Measurement 1075 1078 [.50 mg/dL], acetoacetate [.20 and estimation of GFR in children and 10. Ziegler EE. Milks and formulas for older mmol/L], b-hydroxybutyrate adolescents. Clin J Am Soc Nephrol. infants. J Pediatr. 1990;117(2 pt 2): [.25 mmol/L], pyruvate), which 2009;4(11):1832–1843 S76–S79 could falsely elevate creatinine 3. Mian AN, Schwartz GJ. Measurement 11. Geyer H, Parr MK, Mareck U, Reinhart U, concentrations. However the current and estimation of glomerular filtration Schrader Y, Schänzer W. Analysis enzymatic method that measures rate in children. Adv Chronic Kidney Dis. of non-hormonal nutritional serum creatinine eliminates the 2017;24(6):348–356 supplements for anabolic-androgenic steroids - results of an international measurement of the chromogens. Our 4. Braissant O, Henry H, Béard E, Uldry J. study. Int J Sports Med. 2004;25(2): laboratory uses enzymatic method to Creatine deficiency syndromes and the 124–129 measure serum creatinine. Other importance of creatine synthesis in the inherent pitfalls, such as muscle mass brain. Amino Acids. 2011;40(5): 12. Geyer H, Parr MK, Koehler K, Mareck U, determining the value of serum 1315–1324 Schänzer W, Thevis M. Nutritional supplements cross-contaminated and creatinine and a secretory component 5. Brosnan ME, Brosnan JT. The role of faked with doping substances. J Mass of creatinine elimination in the renal dietary creatine. Amino Acids. 2016; Spectrom. 2008;43(7):892–902 tubule in addition to filtration, are 48(8):1785–1791 also present.2 13. Devries MC, Sithamparapillai A, Brimble 6. Purchas RW, Rutherfurd SM, Pearce PD, KS, Banfield L, Morton RW, Phillips SM. Vather R, Wilkinson BH. Concentrations In this case, we exemplify the Changes in kidney function do not differ in beef and lamb of taurine, carnosine, importance of obtaining a detailed between healthy adults consuming coenzyme Q(10), and creatine. Meat Sci. nutritional intake assessment and use higher- compared with lower- or 2004;66(3):629–637 of a biomarker like cystatin C to help normal-protein diets: a systematic identify the proper treatment of the 7. Weston A. Price Foundation. Formula - review and meta-analysis. J Nutr. 2018; infant, in this case a decision between homemade baby formula. 2001. 148(11):1760–1775

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Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2020/06/15/peds.2 019-2828 References This article cites 12 articles, 1 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2020/06/15/peds.2 019-2828#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Nephrology http://www.aappublications.org/cgi/collection/nephrology_sub Nutrition http://www.aappublications.org/cgi/collection/nutrition_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on October 1, 2021 Elevated Serum Creatinine: But Is It Renal Failure? Molly Wong Vega, Sarah J. Swartz, Sridevi Devaraj and Srivaths Poyyapakkam Pediatrics originally published online June 17, 2020;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/early/2020/06/15/peds.2019-2828

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2020 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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