Serum creatinine is typically used to evaluate kidney function. Yet, it is 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 creatine 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 cystatin C. 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. We highlight the importance of in-depth nutrition assessments and education on the health risks associated with improper formula selection.

Serum creatinine is used as a marker to evaluate kidney function and estimate glomerular filtration rate because of its complete filtration by the kidney.1,2  However, there are disadvantages to using creatinine as an indicator of kidney function. Serum creatinine levels can be influenced by age, sex, muscle mass, diet, and chronic illness.3  Advancements have made the use of cystatin C available as a biomarker in the assessment of glomerular filtration rate. The uses of cystatin C if available are supported by the literature because it appears to follow maturational changes in glomerular filtration rate more closely.3 

Creatinine is formed from creatine. Muscle contains the most significant stores of creatine and creatine phosphate, where they play a critical role in cellular energy metabolism. Creatine is also essential for maintaining energy levels necessary for brain development and is important for neural development.4  Phosphocreatine spontaneously cyclize to form creatine and then breaks down to creatinine. Creatine is synthesized from arginine, glycine, and S-adenosyl methionine primarily in the liver.5  It has been estimated that the infant requirement for creatine is ∼4.26 mmol per week (80 mg per day), taking into account growth and creatine loss.6  De novo synthesis accounts for ∼90% of creatine accretion in infants receiving human milk, with potential decreases in endogenous production in formula-fed infants given higher creatine contents.

In this article, we present the case of a 4-month-old boy with elevated creatinine without previous history of renal impairment receiving a homemade infant formula, which illustrates the need to critically evaluate this biomarker.

A 4-month-old boy, born at 31 weeks (corrected gestational age 8 weeks) with a 5-week NICU stay, with gastroesophageal reflux, presented to the hospital emergency department for evaluation of elevated serum creatinine. He was seen by his pediatrician for his 4-month well-child visit, where his parents informed his physician that they had started him on a custom formula named Weston Price Beef Liver Formula.7  This formula consists of 3 3/4 cup chicken broth, 2 oz beef liver, 5 tablespoons lactose (brand NOW), 1/4 teaspoon Bifidobacterium infantis, 1/4 cup homemade liquid whey, 1 tablespoon coconut oil, 1/2 teaspoon cod liver oil, 1 teaspoon sunflower oil, 2 teaspoons olive oil, and 1/4 teaspoon acerola powder (brand NOW).7  The mother introduced this custom formula without the pediatrician’s knowledge because of concerns related to previous formula intolerance. The infant had been tried on multiple other formulas in conjunction with his pediatrician because of worsening of reflux, constipation, increased fussiness, and nasal congestion. The only other formula that was somewhat agreeable was Alimentum (ready to feed) because it only caused constipation. He had been tolerating the custom formula with no such issues. Because of concern for possible hyponatremia, laboratories were checked, which showed a serum creatinine 1.29 mg/dL (114 μmol/L) with repeat creatinine 1.61 mg/dL (142 μmol/L). The age-based normal value of creatinine for this patient is ∼0.15 to 0.3 mg/dL (15–30 μmol/L). He was seen emergently at this hospital for a recheck, which showed continued increase in creatinine to 2.09 mg/dL (185 μmol/L) and with a blood urea nitrogen of 13 mg/dL.

On examination, the patient was a well-nourished infant with a weight of 6.8 kg (40th percentile; Z score −0.26), length was 57.2 cm (less than the third percentile; Z score −3.21), and head circumference was 40.5 cm (17th percentile; Z score −0.95). Corrected gestational age anthropometrics were weight: 1.825 (96th percentile), head circumference: 1.33 (91st percentile), and length: −0.43 (33rd percentile). He was sleepy but arousable, with a normal blood pressure, moist mucous membranes, and an otherwise unremarkable physical examination. In addition to elevated creatinine, laboratory evaluation revealed mildly elevated serum potassium of 6 mEq/L and mildly elevated phosphorus of 8 mg/dL; the remainder of his electrolytes and blood counts were normal. Additionally, a renal ultrasound revealed both kidneys to be normal in appearance.

The infant’s custom formula was discontinued, and he was started on intravenous maintenance fluids. His repeat laboratory tests 12 hours after starting intravenous fluid showed improvement in creatinine to 0.32 mg/dL (28 μmol/L) and blood urea nitrogen of 8 mg/dL. Serum potassium and phosphorus normalized at 4.1 mEq/L and 5.5 mg/dL. Serum cystatin C sent at the same time as creatinine from both the previous day and next morning sample was normal at 0.8 mg/L.

Obtaining a cystatin C level was instrumental in confirming our hypothesis: intake of a homemade baby formula led to increases in serum creatinine for this patient. We postulate that this patient’s transient rise in serum creatinine was due to inadvertent high dietary creatine intake.8 

High creatine intake could have been achieved by 2 primary sources in this case presentation. First, this homemade baby formula included the use of beef liver. Beef contains the largest percentage of naturally occurring dietary creatine. Estimated maximal creatine content of this homemade formula was 197 mg per 1 L recipe or ∼1500 μmol/L.6  For reference, Edison et al9  reported creatine concentrations of human milk (70 μmol/L) and other common formulas ranging from 10 to 334 μmol/L. Recommendations on the avoidance of cow’s milk as a primary source of nutrition for infants have been centered on development of anemia and its high renal solute load.10  The creatine content of cow’s milk has been reported at 550 μmol/L, meaning this homemade formula could have been ∼3 times higher than the creatine content of cow’s milk.6 

Second, this homemade baby formula was made up of many powders and nutritional supplements, thereby allowing for the potential of creatine contamination of any one of these products. In the United States, the dietary supplement industry is regulated by the Food and Drug Administration, under the provisions of the Dietary Supplement Health and Education Act of 1994. Unlike food stuffs, supplements do not need to be evaluated for efficacy or purity. Many reports exist on contamination of dietary supplements on national and international scale.11,12  Weston Price’s Web site gives brand recommendations, of which none were third party tested at the time of the patient’s emergency center visit.4 

Creatine has been identified as an ergogenic and medical aide that does not lead to kidney failure in adults with normal kidney function.13  It is unknown how higher levels of creatine intake over time would have influenced this infant’s kidney function long term, but given the patient’s elevated potassium and phosphorus alterations, metabolic control was clearly affected, which could have led to life threatening cardiac arrhythmias. Additionally, the higher renal solute load could have had similar consequences related to consumption of high renal solute load milks with the potential for developing dehydration.

Serum creatinine, though the most common biomarker of renal function, has some limitations pertaining to the method of measurement as well as some inherent properties. Jaffe’s method of measuring serum creatinine would also measure noncreatinine chromogens (including glucose, vitamin C, proteins, acetone [>50 mg/dL], acetoacetate [>20 mmol/L], β-hydroxybutyrate [>25 mmol/L], pyruvate), which could falsely elevate creatinine concentrations. However the current enzymatic method that measures serum creatinine eliminates the measurement of the chromogens. Our laboratory uses enzymatic method to measure serum creatinine. Other inherent pitfalls, such as muscle mass determining the value of serum creatinine and a secretory component of creatinine elimination in the renal tubule in addition to filtration, are also present.2 

In this case, we exemplify the importance of obtaining a detailed nutritional intake assessment and use of a biomarker like cystatin C to help identify the proper treatment of the infant, in this case a decision between further evaluation and consideration for dialysis verses simply changing formula. Additionally, it demonstrates the potential risks in providing formulas not regulated by pharmaceutical level manufacturing standards and how we can better educate parents on the risks of improper formula selection.

Ms Wong Vega and Drs Swartz, Devaraj, and Srivaths drafted the initial manuscript and reviewed and revised the manuscript; and all authors approved the final manuscripts submitted and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.