https://imcjms.com Ibrahim Medical College Journal of Medical Science https://imcjms.com/registration/journal_full_text/616 Wed, 30 Sep 2026 12:05:26 +0000 Abstract Background and objective: Autism spectrum disorder (ASD) frequently co-occurs with mitochondrial dysfunction and with restrictive, selective eating. Both may raise serum creatinine. We assessed serum creatinine and urea in Bangladeshi children with ASD. Dietary protein intake was examined as a possible driver of any difference. Materials and methods: This cross-sectional study ran from July 2019 to June 2020 at Dhaka Medical College. We enrolled 30 ASD children (Group A) and 30 matched healthy controls (Group B), aged 5–18 years. Serum creatinine, urea and blood glucose were measured on a Dimension EXL-200 analyzer. Dietary protein intake was estimated from parent-interview food frequency data using the Food Composition Table for Bangladesh. SPSS (Statistical Package for the Social Sciences) version 20.0 was used for analysis; p<0.05 was considered statistically significant. Results: Mean serum creatinine was significantly higher in Group A (0.74 ± 0.22 vs. 0.51 ± 0.13 mg/dl; p<0.001). This exceeded the pediatric reference range. Serum urea (p=0.180) and blood glucose (p=0.657) did not differ. ASD children consumed fish and eggs more frequently (p=0.032 and p=0.041). Mean protein intake was 58.4 ± 12.3 g/day. This exceeded the recommended safe allowance per kilogram. Dietary protein correlated strongly with serum creatinine in Group A (r=0.70; p<0.001; R²=0.49). Socioeconomic profiles were comparable (p=0.287). Conclusion: Serum creatinine was significantly higher in Bangladeshi ASD children than in matched controls and exceeded the pediatric reference range, whereas serum urea and blood glucose were unchanged. The creatinine elevation was strongly correlated with a higher dietary protein intake from preferred fish and egg consumption. Routine serum creatinine monitoring and dietary counseling should be integrated into the standard clinical management of children with ASD. July 2026; Vol. 20(2):004.  DOI: https://doi.org/10.55010/imcjms.20.013 *Correspondence: Asma Sultana Riya, Department of Biochemistry, Institute of Applied Health Sciences (IAHS), Chattogram, Bangladesh Email: asmariya007@gmail.com. © 2026 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License(CC BY 4.0)   Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition defined by a distinct mix of features. These include impaired social communication, repetitive behaviors, highly restricted interests and unusual sensory responses, all beginning early in life. The clinical presentation is markedly heterogeneous across the spectrum. Its global prevalence is close to 1%. Rates are generally higher in high-income countries [1]. Up to 40 percent of affected individuals carry identifiable genetic or metabolic disturbances [2]. Metabolic comorbidities like disruptions in cellular energy production, gastrointestinal physiology and micronutrient homeostasis have been documented in children with ASD [3]. Of these biological findings, mitochondrial dysfunction is the best supported and most often replicated [4,5]. In one case-control study, immune cells from ASD children showed much lower mitochondrial complex I activity. The activity was about two-thirds below that of typically developing children [6]. Cellular energy production normally follows a sequential chain. Glucose is first broken down to pyruvate through glycolysis in the cytosol. Pyruvate is then converted to acetyl-CoA and enters the tricarboxylic acid (TCA) cycle in the mitochondrial matrix. The TCA cycle produces the reduced electron carriers NADH and FADH2. These donate electrons to the electron transport chain (ETC) in the inner mitochondrial membrane. This process drives oxidative phosphorylation and produces ATP [5,7]. In ASD, impairment of ETC complexes I, III and IV reduces the efficiency of this primary ATP-generating pathway [5,6]. To cope with this energy shortfall, cells lean on the creatine kinase/ phosphocreatine (CK/PCr) shuttle as a buffer [8]. In this shuttle, creatine kinase in the mitochondrial intermembrane space uses ATP to convert creatine to phosphocreatine. Cytosolic creatine kinase then regenerates ATP at sites of energy consumption [8,9]. Increased reliance on this shuttle accelerates the non-enzymatic, irreversible dehydration of creatine and phosphocreatine to creatinine [10,11]. Creatinine is the final end product of this pathway. It cannot be reconverted and is excreted by the kidneys [11]. Sustained activation of this pathway therefore increases creatinine production and can raise the serum creatinine concentration [10,11]. Children with ASD are more than five times as likely to have significant feeding problems as typically developing children [12]. This restrictive pattern often narrows food choices to a small group of preferred items [13,14]. Fish and eggs are typically among the most preferred foods, while most vegetables are avoided [14]. In Bangladesh, almost the whole population eats fish. It provides much of the daily animal protein [15]. This selective preference is therefore likely to raise habitual animal-protein and creatine intake. Both fish and eggs are concentrated dietary sources of creatine [16]. Amino acids from digested protein, particularly arginine and glycine, serve as precursors for endogenous creatine biosynthesis via the L-arginine:glycine amidinotransferase (AGAT) and Guanidinoacetate N-methyltransferase (GAMT) enzymatic pathway in the liver and kidney [9]. Creatine-rich foods also directly expand the intracellular creatine pool in muscle, further increasing creatinine output [16]. When dietary intake of animal protein is high, the muscle creatine pool expands and creatinine efflux rises independently of any change in glomerular filtration [16,17]. But urea comes mainly from the urea cycle in the liver. This pathway converts ammonia from amino acid catabolism to urea through enzymatic steps located partly in the mitochondrial matrix and partly in the cytosol [7,11]. Serum urea, being a product of hepatic nitrogen metabolism, is therefore a far less specific reflection of muscle creatine turnover than creatinine [11]. Systemic glucose homeostasis, when intact, helps exclude diabetic nephropathy as a confounding factor in evaluating creatinine changes. Few studies have examined serum creatinine, urea and glucose levels in children with ASD. Earlier case-control studies found no notable change in serum creatinine or urea in this group [18,19]. Findings on blood glucose have been inconsistent, with some reports suggesting lower fasting levels in ASD children compared with controls. None of these studies, however, assessed diet at the same time. They also did not evaluate populations with high habitual fish and animal protein consumption. The mechanism by which dietary protein selectivity and mitochondrial dysfunction together affect renal metabolic markers in ASD is therefore unclear. We measured serum creatinine, serum urea and random blood glucose in Bangladeshi children with ASD and matched healthy controls. Dietary protein intake and socioeconomic characteristics were also quantified. This study asked whether ASD is linked to altered renal metabolic markers. It also examined how far dietary protein selectivity explains any such change.   Materials and methods This study followed a cross-sectional analytical design. Data were collected over one year, from July 2019 to June 2020. It was carried out at the Department of Biochemistry, Dhaka Medical College, Dhaka, Bangladesh. Sixty children between 5 and 18 years of age were recruited using a purposive sampling technique. Group A comprised 30 children with a confirmed diagnosis of ASD. All fulfilled DSM-5 criteria (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) [20]. They were recruited from the outpatient department of NIMH, Dhaka. Group B consisted of 30 apparently healthy children. They were matched for age and body mass index (BMI), with a comparable gender distribution. They were recruited from residential localities in Dhaka city. Children with epilepsy, obsessive-compulsive disorder, attention deficit hyperactivity disorder (ADHD) or any other current psychiatric diagnosis were excluded from both groups. The parent or legal guardian of each child provided written informed consent before any study procedure was undertaken. Five milliliters of venous blood were obtained under aseptic conditions by a trained phlebotomist. The sample was transferred into a dry red-capped tube. It was allowed to clot at ambient temperature for 20 minutes. Serum was obtained after centrifuging the clotted sample at 3,000 rpm over a 10-minute period. Blood glucose at the time of sampling was quantified by the enzymatic hexokinase assay. Kinetic Jaffe method was applied in measurement of serum creatinine. Urea concentration in serum was determined using the enzymatic urease assay. Biochemical analyses were performed on a Dimension EXL-200 automated analyzer housed in the Clinical Pathology department at Dhaka Medical College and Hospital. For normally distributed continuous variables, results are presented as mean ± SD. Between-group differences were evaluated with the unpaired Student's t-test. For categorical data, the Chi-square test was applied; Fisher's exact test was substituted when any expected cell count fell below five. Within Group A, Pearson's product-moment correlation coefficient (r) was calculated to evaluate the linear association between estimated daily protein intake and serum creatinine. The coefficient of determination (R²) was derived to quantify the proportion of creatinine variance attributable to protein intake. All analyses were performed using SPSS version 20.0. Statistical significance was defined as a two-tailed p-value of less than 0.05, corresponding to a 95% confidence level. Results Dietary protein selectivity is a contributing mechanism supported by the present data. ASD children in this study consumed fish and eggs significantly more often than controls [13,14]. This dietary pathway is supported by the strong positive correlation between daily protein intake and serum creatinine observed in Group A, consistent with experimental evidence that a single standardized protein-rich meal measurably raises serum creatinine in humans within hours [17]. Clothier and Absoud (2021) separately highlighted the overlap between ASD and renal pathology in children and called for closer clinical attention to kidney function in this population [25]. The present findings show that serum creatinine elevation can occur in ASD children without overt renal disease. Dietary protein selectivity alone accounted for close to half of the variance in serum creatinine, making it a modifiable target for structured dietary counseling. Random blood glucose did not differ significantly between Group A and Group B, and mean values in both groups fell within the normal reference range. This contrasts with Al-Bazzaz et al. (2020), who reported significantly lower fasting blood glucose in autistic patients compared with controls [26]. In that study, the low fasting glucose was attributed mainly to poor intestinal glucose uptake. The authors linked this to the gut microbial changes and feeding difficulties commonly seen in ASD. The present study measured random rather than fasting blood glucose, and the habitually carbohydrate-rich Bangladeshi diet is likely to keep blood glucose within the normal range. Because hyperglycemia was absent in this cohort, diabetic nephropathy can be excluded as an explanation for the elevated creatinine seen in Group A. Household socioeconomic status was comparable between the two groups, indicating that the higher fish and egg intake among ASD children was not driven by household income or purchasing power. Zimmer et al. (2012) showed that food variety in ASD is shaped by the child's sensory and behavioral characteristics rather than family resources [27]. The food choices observed in this study are consistent with sensory sensitivity and behavioral rigidity rather than socioeconomic factors. Serum urea did not differ significantly between the groups, consistent with Fahmy (2016) and ElBaz et al. (2014) [18,19]. Urea, by contrast, responds only weakly and non-specifically to muscle creatine breakdown [11], which likely explains why it did not track the same dietary influence in this cohort. The small single-center sample is a key limitation. Reliance on parent-reported dietary recall is also a limitation. A larger multi-center study with objective dietary and physical activity measurement is warranted.   Conclusion In summary, serum creatinine was significantly elevated in Bangladeshi ASD children, while serum urea and blood glucose remained within normal limits. High dietary protein intake from preferred fish and egg consumption was the main contributing factor identified in this study. Routine serum creatinine monitoring and dietary counseling should be incorporated into standard clinical management of children with ASD.   Ethical statement Ethical clearance was obtained from the Ethical Review Committee, Dhaka Medical College [Memo No. ERC-DMC/ECC/2020/84]. Permission for blood sample collection from NIMH was granted by the Director-cum-Professor, NIMH [Memo No. NIMH/2020/342]. Informed written consent for participation and publication of anonymized data was obtained from the parent or legal guardian of each participant.   Conflict of interest The authors declare no competing financial or non-financial interests in relation to this work.   Funding Sources The author(s) received no external funding was received for this study.   Acknowledgments The authors acknowledge the children who participated in this study and their parents and guardians for their cooperation during blood collection and the dietary interview.   References 1.     Lord C, Brugha TS, Charman T, Cusack J, Dumas G, Frazier T, et al. Autism spectrum disorder. Nat Rev Dis Primers. 2020; 6(1): 5. doi: 10.1038/s41572-026-00706-w. 2.     Genovese A, Butler MG. Clinical assessment, genetics, and treatment approaches in autism spectrum disorder (ASD). Int J Mol Sci. 2020; 21(13): 4726. doi: 10.3390/ijms21134726. 3.     Kohane IS, McMurry A, Weber G, MacFadden D, Rappaport L, Kunkel L, et al. 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