Ibuprofen Use as Emerging Determinants of Acute Kidney Injury in Pakistani Children: Evidence from a Tertiary Care Center

Global Burden and Pediatric Challenges Kidney disease in children is a complex and emerging global health issue that is more common than generally perceived. However, prevalence rates vary significantly across different healthcare systems. In developed nations, chronic kidney disease (CKD) affects approximately 1 in 1,000 children; however, in developing countries, the incidence is believed to be significantly higher due to a greater burden of untreated infections and limitations in early diagnostic capabilities (Groothoff, 2023). Unlike adults, children with kidney disease face unique developmental challenges, including growth retardation and cognitive delays, which can severely impact their long-term quality of life (Tsochatzis et al., 2014). The disease presentation is often nonspecific, manifesting as fatigue or poor growth, which frequently leads to delayed diagnosis until significant renal damage has already occurred (yen Tay et al., 2020).

From Congenital to Acquired Risks Traditionally, the etiology of pediatric kidney disease has been dominated by congenital anomalies of the kidney and urinary tract (CAKUT) and genetic disorders. However, recent epidemiological trends indicate a shift toward acquired causes driven by environmental and lifestyle factors. Acute Kidney Injury (AKI), which is often precipitated by infections, dehydration, and nephrotoxic exposure, is becoming a critical area of concern. While AKI was previously considered a temporary condition, contemporary research suggests it acts as a gateway to long-term chronic pathology if not managed effectively (Patel et al., 2023). Understanding the transition from acute insults to chronic disease is essential for preventing End-Stage Renal Disease (ESRD) in later life.

The Role of Nephrotoxic Medications and Lifestyle Among the acquired risk factors, the unregulated use of nephrotoxic medications poses a severe threat to pediatric renal health. Non-steroidal anti-inflammatory drugs (NSAIDs), particularly ibuprofen, are widely used for fever and pain management in children. Studies indicate that these drugs can cause significant kidney damage over time, especially in children with pre-existing vulnerabilities or volume depletion (Hernández et al., 2018). Evidence has identified NSAID use as a leading cause of pediatric AKI in emergency admissions, highlighting the dangers of self-medication (Aljinović-Vučić, 2025). Furthermore, modern lifestyle shifts, such as increased sedentary behavior and the consumption of high-phosphate cold drinks, are exacerbating metabolic risks that may compromise renal perfusion and function.

Rationale and local gap analysis despite the rising incidence of renal dysfunction, there is a paucity of comprehensive data regarding the risk profile of children in Pakistan, particularly in industrial districts like Faisalabad. Most existing literature focuses on adult populations or specific congenital defects, leaving a gap in understanding how modifiable lifestyle factors, such as ibuprofen usage, hydration habits, and physical inactivity, contribute to the differential diagnosis of AKI versus CKD in local pediatric cohorts. Identifying these specific determinants is crucial, as early intervention can significantly reduce the risk of long-term complications and improve survival rates (Baracaldo-Santamaría et al., 2022, Aljinović-Vučić, 2025).

This study was conducted to evaluate the prevalence of acute and chronic kidney disease among children in District Faisalabad and to determine the statistical association of clinical, lifestyle, and familial risk factors with renal outcomes. Specifically, this research aims to highlight the impact of modifiable risks, such as ibuprofen exposure and sedentary lifestyle, to inform better public health strategies and clinical practices in the region.

Figure 1: Study enrollment and Diagnostic Classification

Data Collection and Risk Assessment

Data were collected using a structured, pre-tested questionnaire administered to parents or guardians, supplemented by a comprehensive review of medical records7. The instrument was designed to capture three specific domains of risk:

1. Clinical History: Documentation of previous urinary tract infections (UTIs), diabetes, hypertension, and family history of renal disease.
2. Medication Exposure: Specific inquiry into the frequency of nephrotoxic drug use, particularly non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, and the use of unverified herbal remedies.
3. Lifestyle and Dietary Habits: Assessment of daily water intake (hydration status), consumption of sugar-sweetened beverages (cold drinks), and physical activity levels (sedentary behavior vs. active play).

Laboratory and Diagnostic Protocol

All participants underwent a standardized clinical evaluation. Renal function was assessed via serum creatinine and blood urea nitrogen (BUN) measurements, alongside urinalysis to detect proteinuria or hematuria. Renal ultrasonography was performed to evaluate kidney structure and rule out anatomical defects. The Estimated Glomerular Filtration Rate (eGFR) was calculated using age-appropriate formulas to classify the severity of kidney dysfunction. Based on these clinical and laboratory findings, patients were stratified into two diagnostic groups: Acute Kidney Injury (AKI) or chronic kidney disease (CKD).

Statistical Analysis

Data were processed and analyzed using SPSS (Statistical Package for the Social Sciences) version 2515. Descriptive statistics (frequencies and percentages) were used to summarize demographic and clinical profiles16. The core analysis involved the Chi-square test to determine the association between categorical risk factors (e.g., ibuprofen use, sedentary lifestyle) and the type of kidney disease (AKI vs. CKD). A p-value of less than 0.05 was considered statistically significant.

The findings of this study provide critical insights into the shifting landscape of pediatric nephrology in District Faisalabad. The most striking observation is the high prevalence of Acute Kidney Injury (AKI), which accounted for 71% of cases (Tahir et al., 2021). This suggests that pediatric renal failure in this region is primarily driven by acute, potentially reversible insults rather than long-standing congenital or genetic pathologies.

The Nephrotoxic Burden: Ibuprofen and AKI

The most clinically significant finding of this research is the strong association between ibuprofen exposure and AKI (P=0.049). With 69% of the total cohort and an alarming 77.6% of AKI patients reporting significant ibuprofen use, the data points toward a crisis of NSAID-induced nephrotoxicity. Ibuprofen acts by inhibiting prostaglandin synthesis, which can lead to renal vasoconstriction and reduced glomerular filtration, particularly in children who may already be experiencing mild dehydration or infection (Shao et al., 2021, Lin et al., 2022). Our results mirror global concerns regarding the over-the-counter availability of NSAIDs; however, the prevalence in our study is notably higher than reported in Western cohorts, suggesting a localized trend of self-medication or inadequate parental awareness regarding dosage and renal safety.

Lifestyle Determinants: Sedentary Behavior and Diet

This study highlights a paradigm shift where lifestyle-related factors are now surfacing as "highly significant" determinants of pediatric renal health (P=0.010) (DI APERTURA and ESERCIZIO, 2022). The 60% prevalence of sedentary behavior suggests that physical inactivity is no longer just an adult metabolic concern but a pediatric renal risk factor. Furthermore, the significant association with cold drink consumption (P=0.036) underscores the impact of high-fructose corn syrup and phosphoric acid found in carbonated beverages (Sigala, 2020). These substances are known to induce hyperuricosuria and oxidative stress in renal tissues. The finding that 58% of children regularly consume these drinks calls for immediate public health interventions targeting school-based nutrition and dietary habits.

Demographic Vulnerabilities

The data revealed a distinct female predominance (59%) and a peak incidence in late adolescence (16–20 years, 31%) (Abreu et al., 2018). The adolescent peak may be attributed to increased autonomy in dietary and medication choices, often leading to poor nutritional habits and higher self-administration of analgesics like ibuprofen. Additionally, the finding that 58% of patients reside in rural areas suggests that limited access to specialized pediatric care and a reliance on local pharmacies for symptomatic relief may exacerbate the transition from simple infections to acute renal failure (Lynn et al., 2016).

Traditional vs. Emerging Risk Factors

Interestingly, traditional risk factors such as Diabetes (P=0.326) and Family History (P=1.000) did not show statistical significance in differentiating between AKI and CKD in this cohort (Zidan, 2023, Luo et al., 2025). This indicates that while genetics and systemic diseases are important, the immediate driver of the pediatric renal burden in Faisalabad is overwhelmingly environmental and behavioral. This acquired nature of the disease provides a unique opportunity for prevention through community education and pharmaceutical regulation.

Our findings align with recent studies suggesting that AKI is a major precursor to CKD if not managed early. The significant p-values for modifiable factors support the "AKI-to-CKD continuum" theory, where repeated acute insults such as multiple episodes of NSAID-induced stress eventually lead to permanent nephron loss.

This study underscores a critical transition in pediatric nephrology within the Faisalabad region, where the high prevalence of Acute Kidney Injury (71%) is significantly driven by modifiable environmental factors rather than solely by congenital pathologies. The statistically significant associations identified between renal impairment and excessive ibuprofen use (P=0.049), sedentary behavior (P=0.010), and high consumption of sugar-sweetened beverages (P=0.036) highlight a "triple threat" of pharmacological and lifestyle-related risks. These findings mandate an urgent shift toward preventative public health strategies, specifically targeting parental education on NSAID safety and the promotion of active lifestyles, to mitigate the risk of acute insults progressing into lifelong chronic kidney disease.

1.     Abreu, N., Dias, I., Cascais, M., Luz, A. and Moleiro, P. (2018) What are the most frequent diagnoses in adolescence? The reality of an Adolescent Medicine Clinic. einstein (São Paulo), 16, eAO4225.

2.     Aljinović-Vučić, V. (2025) Self-medication as a global health concern: overview of practices and associated factors—a narrative review. In Healthcare: MDPI, pp. 1872.

3.     Baracaldo-Santamaría, D., Pabón-Londoño, S. and Rojas-Rodriguez, L.C. (2022) Drug safety of frequently used drugs and substances for self-medication in COVID-19. Therapeutic advances in drug safety, 13, 20420986221094141.

4.     DI APERTURA, S. and ESERCIZIO, P.E. (2022) XII National Congress SISMES Padua, 8–10 October, 2021.

5.     Groothoff, J.W. (2023) Long-term outcome of kidney failure in children. In Pediatric Kidney Disease: Springer, pp. 1937-1962.

6.     Hernández, D., Chang, D., Hutchinson, C., Hill, E., Almonte, A., Burns, R., Shepard, P., Gonzalez, I., Reissig, N. and Evans, D. (2018) Public housing on the periphery: Vulnerable residents and depleted resilience reserves post-Hurricane Sandy. Journal of urban health, 95, 703-715.

7.     Lin, S.X., Phillips, T., Culliford, D., Edwards, C., Holroyd, C., Ibrahim, K., Barrett, R., Howard, C., Johnson, R. and Adams, J. (2022) Characterising risk of non-steroidal anti-inflammatory drug-related acute kidney injury: a retrospective cohort study. BJGP open, 6.

8.     Luo, P., Feng, J., Li, Y., Zou, Y., Zhu, X., Sun, L. and Li, B. (2025) Risk factors associated with the failure of day surgery for total knee arthroplasty a multivariate logistic regression analysis. Frontiers in Surgery, 12, 1597068.

9.     Lynn, D.D., Umari, T., Dunnick, C.A. and Dellavalle, R.P. (2016) The epidemiology of acne vulgaris in late adolescence. Adolescent health, medicine and therapeutics, 13-25.

10.   Patel, M., Hornik, C., Diamantidis, C., Selewski, D.T. and Gbadegesin, R. (2023) Patient level factors increase risk of acute kidney disease in hospitalized children with acute kidney injury. Pediatric Nephrology, 38, 3465-3474.

11.   Shao, Q.-h., Yin, X.-d., Liu, H.-x., Zhao, B., Huang, J.-q. and Li, Z.-l. (2021) Kidney injury following ibuprofen and acetaminophen: a real-world analysis of post-marketing surveillance data. Frontiers in Pharmacology, 12, 750108.

12.   Sigala, D.M. (2020) Sugar Sweetened Beverage Consumption and the Risk of Metabolic Disease in Young Adults: University of California, Davis.

13.   Tahir, M.J., Malik, N.I., Ullah, I., Khan, H.R., Perveen, S., Ramalho, R., Siddiqi, A.R., Waheed, S., Shalaby, M.M.M. and De Berardis, D. (2021) Internet addiction and sleep quality among medical students during the COVID-19 pandemic: A multinational cross-sectional survey. PloS one, 16, e0259594.

14.   Tsochatzis, E.A., Bosch, J. and Burroughs, A.K. (2014) Liver cirrhosis. The Lancet, 383, 1749-1761.

15.   yen Tay, S., Freeman, K. and Baird, R. (2020) Clinical manifestations associated with Bartonella henselae infection in a tropical region. The American journal of tropical medicine and hygiene, 104, 198.

16.   Zidan, A.m.N. (2023) COMPARISON OF THE NEUROLOGICAL ADVERSE EVENTS AND CHANGES IN ELECTROLYTES LEVELS BETWEEN PANTOPRAZOLE AND FAMOTIDINE: A PROSPECTIVE OBSERVATIONAL STUDY: Faculty of Graduate Studies COMPARISON OF THE NEUROLOGICAL ADVERSE EVENTS