Prospective Study of Urinary Stone Formation in Pediatric Patients with Acquired Brain Injury: A Focus on Incidence and Analysis of Risk Factors
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Population Characteristics
3.1.1. Clinical Characteristics
3.1.2. Enteral Nutrition Characteristics
3.2. Incidence of Urolithiasis and Associated Clinical Factors
3.2.1. Incidence of Urolithiasis and Associations with Single Clinical Factors
3.2.2. Associations of Urolithiasis with All Clinical Factors
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Araya, C.E.; Hani, A.H.B. Kidney Stones: Risks, Prevention, and Management in Cerebral Palsy. In Cerebral Palsy, 2nd ed.; Miller, F., Bachrach, S., Lennon, N., O’Neil, M.E., Eds.; Springer Nature: Berlin/Heidelberg, Germany, 2020; pp. 871–883. [Google Scholar]
- Schwaderer, A.L.; Oduguwa, A.; Kusumi, K. Urinary stone disease in pediatric and adult metabolic bone clinic patients. Urolithiasis 2018, 46, 173–178. [Google Scholar] [CrossRef] [PubMed]
- Tozsin, A.; Akdere, H.; Guven, S.; Ahmed, K. A systematic review on urolithiasis in children with neurological disorders. World J. Urol. 2024, 42, 635. [Google Scholar] [CrossRef]
- Ramachandra, P.; Palazzi, K.L.; Holmes, N.M.; Chiang, G. Children with spinal abnormalities have an increased health burden from upper tract urolithiasis. Urology 2014, 83, 1378–1382. [Google Scholar] [CrossRef] [PubMed]
- Gök, A.; Saygılı, S.K.; Kuruğoğlu, S.; Saltık, S.; Canpolat, N. Children with Type 1 Spinal Muscular Atrophy Are at Increased Risk for Nephrolithiasis. Pediatr. Neurol. 2024, 150, 32–36. [Google Scholar] [CrossRef]
- DeFoor, W.; Nehus, E.; Schulte, M.; Huesman, S.; Libs, A.; Niehaus, R.; Devarajan, P. Enteral nutrition and the risk of nephrolithiasis in complex pediatric patients. J. Pediatr. Urol. 2022, 18, 743.e1–743.e6. [Google Scholar] [CrossRef] [PubMed]
- El-Aziz El-Gamasy, M.A.; Darwish, A.H.; Al-Shahawy, A.K.; Eissa, G.E. Prevalence and risk factors of urolithiasis in children with cerebral palsy. J. Adv. Med. Med. Res. 2020, 32, 24–39. [Google Scholar]
- Fernandez, N.; Silverii, H.; Dangle, P.; Yonekawa, K. Atypical clinical presentation and management of urinary stone disease in non-verbal non-ambulatory children. J. Pediatr. Urol. 2023, 19, 560.e1–560.e6. [Google Scholar] [CrossRef]
- Ishikawa, N.; Tani, H.; Kobayashi, Y.; Kato, A.; Kobayashi, M. High Incidence of Renal Stones in Severely Disabled Children with Epilepsy Treated with Topiramate. Neuropediatrics 2019, 50, 160–163. [Google Scholar] [CrossRef]
- Al-Hayek, S.; Schwen, Z.R.; Jackman, S.V.; Averch, T.D. The impact of obesity on urine composition and nephrolithiasis management. J. Endourol. 2013, 27, 379–383. [Google Scholar] [CrossRef]
- Mahmoud, A.A.; Rizk, T.; El-Bakri, N.K.; Riaz, M.; Dannawi, S.; Al Tannir, M. Incidence of kidney stones with topiramate treatment in pediatric patients. Epilepsia 2011, 52, 1890–1893. [Google Scholar] [CrossRef]
- Corbin Bush, N.; Twombley, K.; Ahn, J.; Oliveira, C.; Arnold, S.; Maalouf, N.M.; Sakhaee, K. Prevalence and spot urine risk factors for renal stones in children taking topiramate. J. Pediatr. Urol. 2013, 9 Pt A, 884–889. [Google Scholar] [CrossRef]
- Tori, J.A.; Kewalramani, L.S. Urolithiasis in children with spinal cord injury. Spinal Cord 1979, 16, 357–365. [Google Scholar] [CrossRef]
- Levi, R.; Hultling, C.; Nash, M.S.; Seiger, A. The Stockholm spinal cord injury study: 1. Medical problems in a regional SCI population. Paraplegia 1995, 33, 308–315. [Google Scholar] [CrossRef] [PubMed]
- Stogov, M.V.; Schurova, E.N.; Kireieva, E.A. The search after prognostic tests of development of urolithiasis of patients with vertebro-cerebrospinal trauma. Klin. Lab. Diagn. 2015, 60, 28–30. [Google Scholar]
- Thibaut, A.; Aloisi, M.; Dreessen, J.; Alnagger, N.; Lejeune, N.; Formisano, R. Neuro-orthopaedic assessment and management in patients with prolonged disorders of consciousness: A review. NeuroRehabilitation 2024, 54, 75–90. [Google Scholar] [CrossRef] [PubMed]
- Estraneo, A.; Pascarella, A.; Masotta, O.; Bartolo, M.; Pistoia, F.; Perin, C.; Marino, S.; Lucca, L.; Pingue, V.; Casanova, E.; et al. Multi-center observational study on occurrence and related clinical factors of neurogenic heterotopic ossification in patients with disorders of consciousness. Brain Inj. 2021, 35, 530–535. [Google Scholar] [CrossRef]
- Falsetti, P.; Acciai, C.; Palilla, R.; Carpinteri, F.; Patrizio, C.; Lenzi, L. Bedside ultrasound in early diagnosis of neurogenic heterotopic ossification in patients with acquired brain injury. Clin. Neurol. Neurosurg. 2011, 113, 22–27. [Google Scholar] [CrossRef] [PubMed]
- Pozzi, M.; Locatelli, F.; Galbiati, S.; Beretta, E.; Carnovale, C.; Clementi, E.; Strazzer, S. Relationships between enteral nutrition facts and urinary stones in a cohort of pediatric patients in rehabilitation from severe acquired brain injury. Clin. Nutr. 2019, 38, 1240–1245. [Google Scholar] [CrossRef]
- Adams, R.S.; Corrigan, J.D.; Dams-O’Connor, K. Opioid Use among Individuals with Traumatic Brain Injury: A Perfect Storm? J. Neurotrauma 2020, 37, 211–216. [Google Scholar] [CrossRef]
- Pozzi, M.; Conti, V.; Locatelli, F.; Galbiati, S.; Radice, S.; Citerio, G.; Clementi, E.; Strazzer, S. Paroxysmal Sympathetic Hyperactivity in Pediatric Rehabilitation: Clinical Factors and Acute Pharmacological Management. J. Head Trauma Rehabil. 2015, 30, 357–363. [Google Scholar] [CrossRef]
- EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA). Dietary reference values for sodium. EFSA J. Eur. Food Saf. Auth. 2019, 17, e05778. [Google Scholar]
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Dietary reference values for potassium. EFSA J. Eur. Food Saf. Auth. 2016, 14, e04592. [Google Scholar]
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for magnesium. EFSA J. Eur. Food Saf. Auth. 2015, 13, 4186. [Google Scholar]
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for calcium. EFSA J. Eur. Food Saf. Auth. 2015, 13, 4101. [Google Scholar]
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for protein. EFSA J. Eur. Food Saf. Auth. 2012, 10, 2557. [Google Scholar]
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on Dietary Reference Values for vitamin C. EFSA J. Eur. Food Saf. Auth. 2013, 11, 3418. [Google Scholar]
- Heinen, F.; Bonfert, M.; Kaňovský, P.; Schroeder, A.S.; Chambers, H.G.; Dabrowski, E.; Geister, T.L.; Hanschmann, A.; Althaus, M.; Banach, M.; et al. Spasticity-related pain in children/adolescents with cerebral palsy. Part 1: Prevalence and clinical characteristics from a pooled analysis. J. Pediatr. Rehabil. Med. 2022, 15, 129–143. [Google Scholar] [CrossRef] [PubMed]
- Peck, J.; Urits, I.; Crane, J.; McNally, A.; Noor, N.; Patel, M.; Berger, A.A.; Cornett, E.M.; Kassem, H.; Kaye, A.D.; et al. Oral Muscle Relaxants for the Treatment of Chronic Pain Associated with Cerebral Palsy. Psychopharmacol. Bull. 2020, 50 (Suppl. 1), 142–162. [Google Scholar]
- Martens, G.; Laureys, S.; Thibaut, A. Spasticity Management in Disorders of Consciousness. Brain Sci. 2017, 7, 162. [Google Scholar] [CrossRef]
- Zhang, B.; Karri, J.; O’Brien, K.; DiTommaso, C.; Kothari, S.; Li, S. Spasticity Management in Persons with Disorders of Consciousness. PM R J. Inj. Funct. Rehabil. 2021, 13, 657–665. [Google Scholar] [CrossRef]
- Frigerio, S.; Molteni, E.; Colombo, K.; Pastore, V.; Fedeli, C.; Galbiati, S.; Strazzer, S. Neuropsychological assessment through Coma Recovery Scale-Revised and Coma/Near Coma Scale in a sample of pediatric patients with disorder of consciousness. J. Neurol. 2023, 270, 1019–1029. [Google Scholar] [CrossRef]
- Edmond, A.; McKay, O.; Mehta, N.; Dabaghian, L.; Yonclas, P. Spasticity management and resolution of paroxysmal sympathetic hyperactivity in the acute care setting: A case series. Brain Inj. 2022, 36, 817–821. [Google Scholar] [CrossRef] [PubMed]
- Letzkus, L.; Keim-Malpass, J.; Kennedy, C. Paroxysmal sympathetic hyperactivity: Autonomic instability and muscle over-activity following severe brain injury. Brain Inj. 2016, 30, 1181–1185. [Google Scholar] [CrossRef] [PubMed]
- Pozzi, M.; Galbiati, S.; Locatelli, F.; Carnovale, C.; Radice, S.; Strazzer, S.; Clementi, E. Drug Use in Pediatric Patients Admitted to Rehabilitation for Severe Acquired Brain Injury: Analysis of the Associations with Rehabilitation Outcomes. Paediatr. Drugs 2021, 23, 75–86. [Google Scholar] [CrossRef] [PubMed]
- Chiavaroli, F.; Derraik, J.G.; Zani, G.; Lavezzi, S.; Chiavaroli, V.; Sherwin, E.; Basaglia, N. Epidemiology and clinical outcomes in a multicentre regional cohort of patients with severe acquired brain injury. Disabil. Rehabil. 2016, 38, 2038–2046. [Google Scholar] [CrossRef]
- Marsden, J.; Stevenson, V.; Jarrett, L. Treatment of spasticity. Handb. Clin. Neurol. 2023, 196, 497–521. [Google Scholar]
- McKenna, M.C.; Scafidi, S.; Robertson, C.L. Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns. Neurochem. Res. 2015, 40, 2527–2543. [Google Scholar] [CrossRef]
- Caldwell, S.B.; Wilson, J.S.; Smith, D.; McCann, J.P.; Walsh, I.K. Bladder continence management in adult acquired brain injury. Disabil. Rehabil. 2014, 36, 959–962. [Google Scholar] [CrossRef]
- Leary, S.M.; Liu, C.; Cheesman, A.L.; Ritter, A.; Thompson, S.; Greenwood, R. Incontinence after brain injury: Prevalence, outcome and multidisciplinary management on a neurological rehabilitation unit. Clin. Rehabil. 2006, 20, 1094–1099. [Google Scholar] [CrossRef]
- Bishop, K.; Momah, T.; Ricks, J. Nephrolithiasis. Prim. Care 2020, 47, 661–671. [Google Scholar] [CrossRef]
- Gregory, T.M.; Moreno, E.C.; Patel, J.M.; Brown, W.E. Solubility of β-Ca3(PO4)2 in the system Ca(OH)2−H3PO4−H2O at, 5, 15, 25, 37 °C. J. Res. Natl. Bur. Stand. A Phys. Chem. 1974, 78A, 667–674. [Google Scholar] [CrossRef] [PubMed]
- Sutor, T.W.; Kura, J.; Mattingly, A.J.; Otzel, D.M.; Yarrow, J.F. The Effects of Exercise and Activity-Based Physical Therapy on Bone after Spinal Cord Injury. Int. J. Mol. Sci. 2022, 23, 608. [Google Scholar] [CrossRef] [PubMed]
Microorganism | Whole Cohort | Patients with Urolithiasis |
---|---|---|
E. faecalis | 6 (12.5%) | 2 pre-existing |
E. coli | 4 (8.3%) | 1 pre-existing 1 new occurrence |
K. pneumoniae | 4 (8.3%) | 2 new occurrences |
P aeruginosa | 2 (4.2%) | 0 |
C. koseri | 1 (2.1%) | 1 pre-existing |
M. morganii | 1 (2.1%) | 0 |
Patient Age | Na | K | Mg | Ca | Proteins | Vitamin C |
---|---|---|---|---|---|---|
6–12 mo | 200 | 750 | 80 | 280 | 660/kg | 20 |
1–3 y | 1100 | 800 | 170 | 450 | 20 | |
4–6 y | 1300 | 1100 | 230 | 800 | 30 | |
7–10 y | 1700 | 1800 | 230 | 800 | 45 | |
11–14 y | 2000 | 2700 | 300 | 1150 | 70 | |
15–17 y | 2000 | 3500 | 300 | 1150 | 100 |
Clinical Variable | No Urolithiasis | Urolithiasis | p 1 | |||
---|---|---|---|---|---|---|
Unit | Mean | SD | Mean | SD | ||
Age | years | 8.4 | 1.1 | 12.6 | 1.5 | 0.050 |
Weight | kg | 26.7 | 3.2 | 38.0 | 4.5 | 0.06 |
ABI etiology | 0.18 | |||||
Trauma | 22.9% | 46.2% | ||||
Anoxia/ischemia | 22.9% | 23.1% | ||||
Stroke | 11.4% | 23.1% | ||||
Encephalopathy | 31.4% | 7.7% | ||||
Other | 11.4% | 0% | ||||
GCS—acute | \ | 5.7 | 3.3 | 6.2 | 3.8 | 0.67 |
GCS—subacute | \ | 10.0 | 0.4 | 9.3 | 0.8 | 0.43 |
Tracheostomy | yes | 42.9% | 76.9% | 0.036 | ||
Oral feeding | yes | 8.6% | 0% | 0.43 | ||
Catheterism | yes | 14.3% | 38.5% | 0.19 | ||
Gallstones | yes | 8.6% | 15.4% | 0.19 | ||
Intense physical activity before ABI | yes | 28.6% | 69.2% | 0.037 | ||
Bedridden after ABI | yes | 94.3% | 100% | 0.68 | ||
Nutrition | ||||||
Water intake | mL/d | 614 | 277 | 908 | 444 | 0.008 |
Na | mg/kg/d | 39.2 | 29.3 | 31.9 | 21.3 | 0.88 |
K | mg/kg/d | 49.1 | 18.9 | 42.9 | 18.9 | 0.55 |
Mg | mg/kg/d | 5.5 | 2.5 | 5.6 | 3.0 | 0.31 |
Ca | mg/kg/d | 33.1 | 18.9 | 29.9 | 14.5 | 0.65 |
Vitamin C | mg/kg/d | 5.0 | 2.9 | 3.8 | 1.5 | 0.14 |
Proteins | mg/kg/d | 1.3 | 0.6 | 1.1 | 0.3 | 0.40 |
Blood exams | ||||||
Na | mmol/L | 139.4 | 4.8 | 139.2 | 2.7 | 0.88 |
K | mmol/L | 4.3 | 0.5 | 4.4 | 0.4 | 0.56 |
Cl | mmol/L | 101.6 | 4.2 | 100.5 | 2.7 | 0.38 |
Ca | mmol/L | 9.8 | 0.8 | 9.9 | 0.6 | 0.65 |
Mg | mmol/L | 2.0 | 0.3 | 1.9 | 0.2 | 0.31 |
P | mmol/L | 4.7 | 1.5 | 4.8 | 0.6 | 0.89 |
Parathormone | pg/mL | 10.6 | 10.3 | 5.2 | 2.9 | 0.15 |
Vitamin D | ng/mL | 20.5 | 10.1 | 43.0 | 57.5 | 0.22 |
Alkaline phosphatase | U/L | 159.7 | 93.5 | 107.7 | 43.0 | 0.10 |
Uric acid | mg/dL | 3.4 | 1.3 | 3.3 | 1.7 | 0.95 |
Urine exams | ||||||
Urine pH | \ | 7.0 | 0.7 | 7.5 | 0.5 | 0.024 |
Urinary tract infections | yes | 31.4% | 53.8% | 0.15 | ||
Antiepileptic drugs use | ||||||
Lamotrigine daily dose | mg/kg | 0 | 0 | 0.17 | 0.97 | 0.33 |
Levetiracetam daily dose | mg/kg | 19.9 | 2.7 | 16.6 | 2.9 | 0.26 |
Oxcarbazepine daily dose | mg/kg | 0.64 | 4.64 | 0.41 | 2.34 | 0.79 |
Phenobarbital daily dose | mg/kg | 1.1 | 2.5 | 0.5 | 1.3 | 0.10 |
Topiramate daily dose | mg/kg | 0.11 | 0.83 | 0.30 | 1.72 | 0.51 |
Valproic acid daily dose | mg/kg | 4.0 | 12.0 | 1.3 | 7.2 | 0.18 |
Variable | p-Value | OR 1 | 95% C.I.s |
---|---|---|---|
subacute GCS | 0.007 | 0.68 | 0.51–0.90 |
Intense physical activity before ABI: yes | 0.012 | 5.12 | 1.43–18.40 |
K blood levels mmol/l | 0.021 | 4.41 | 1.26–15.48 |
Catheterism: yes | 0.030 | 5.59 | 1.18–26.58 |
Urine pH | 0.048 | 2.40 | 1.01–5.74 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Galbiati, S.; Locatelli, F.; Storm, F.A.; Pozzi, M.; Strazzer, S. Prospective Study of Urinary Stone Formation in Pediatric Patients with Acquired Brain Injury: A Focus on Incidence and Analysis of Risk Factors. Nutrients 2025, 17, 883. https://doi.org/10.3390/nu17050883
Galbiati S, Locatelli F, Storm FA, Pozzi M, Strazzer S. Prospective Study of Urinary Stone Formation in Pediatric Patients with Acquired Brain Injury: A Focus on Incidence and Analysis of Risk Factors. Nutrients. 2025; 17(5):883. https://doi.org/10.3390/nu17050883
Chicago/Turabian StyleGalbiati, Sara, Federica Locatelli, Fabio Alexander Storm, Marco Pozzi, and Sandra Strazzer. 2025. "Prospective Study of Urinary Stone Formation in Pediatric Patients with Acquired Brain Injury: A Focus on Incidence and Analysis of Risk Factors" Nutrients 17, no. 5: 883. https://doi.org/10.3390/nu17050883
APA StyleGalbiati, S., Locatelli, F., Storm, F. A., Pozzi, M., & Strazzer, S. (2025). Prospective Study of Urinary Stone Formation in Pediatric Patients with Acquired Brain Injury: A Focus on Incidence and Analysis of Risk Factors. Nutrients, 17(5), 883. https://doi.org/10.3390/nu17050883