Abstract

Objectives: The aim of this study was to investigate the prevalence of renal anomalies in a large cohort of children with spina bifida and review the information in the literature.

Patients and methods: Between January 2005 and February 2025, a total of 1,039 children (499 males, 540 females; mean age: 4.7±3.1 years; range, 4 days and 17 years) with the diagnosis of spina bifida and spina bifida occulta who were under follow-up within the last 20 years were included in the study. These patients were evaluated for the presence of congenital anomalies of kidney and urinary tract (CAKUT). Age, sex, any urinary anomaly detected with ultrasonography and scintigraphy were noted. English literature was also reviewed the studies reporting the association of spina bifida and CAKUT.

Results: Of all patients, 17 had renal rotational anomaly and 13 had horse-shoe kidney. Nine patients had renal agenesis. Three patients had cross-renal ectopia, while one patient had ureterocele and another patient had ureteropelvic junction obstruction. The total number of patients with congenital renal anomalies associating with spina bifida was found to be 44 with a prevalence of 4.23% in this cohort.

Conclusion: This cohort seems to have the largest patient population reported in a single center on this subject. The prevalence of CAKUT is increased in patients with spina bifida compared to general population. The cause of this increase may be the close embryological background of two systems. Awareness of such a clinical entity may promote the renal protective approach in patients with spina bifida.

Introduction

Spina bifida is a congenital spinal anomaly characterized by defective closure of neural tube during embryogenesis. This complex malformation is associated not only with neurogenic bladder dysfunction (NBD), but also with a broad spectrum of congenital anomalies of kidney and urinary tract (CAKUT). Vertebral bodies start to develop at third weeks of gestation with the formation of notochord. These somites further develop to form vertebral bony structures. During this period paraxial mesoderm and intermediate mesoderm lie next to the notochord. Paraxial mesoderm is responsible for the formation of the vertebrae, as well as the dermis of the skin, striated skeletal muscle, muscles of the head and connective tissue. Renal development starts with pronephros which is formed from intermediate mesoderm.[1,2] Disruptions during the critical period of neural tube closure (Weeks 3 to 4 of gestation) can disturb the intricate process of mesodermal differentiation, leading to concurrent anomalies in both systems.[1] Typically, CAKUT include renal dysplasia, unilateral renal agenesis, ectopic kidneys, collecting system duplications, ureteral malformations, and even structural bladder abnormalities.[3,4] The occurrence of these malformations highlights the shared embryological origins of the spinal cord and the urinary tract.

Congenital renal anomalies, even without NBD due to spina bifida, are clinically important as they comprise 30 to 40% of all children with chronic kidney disease worldwide.[5] Therefore, the association of both anomalies clearly increases the potential lifelong risk of renal impairment in these patients. The exact prevalence of congenital renal anomalies associating with spina bifida is currently unknown. There are conflicting data in the literature regarding a prevalence rate of between 2 and 17.8%.[3,6-9] In the present study, we aimed to investigate the prevalence of congenital renal anomalies associating with spina bifida, which, to the best of our knowledge, is the largest single-center pediatric case series in the literature.

Patients and Methods

This single-center, cross-sectional, observational, retrospective study was conducted at Demiroğlu Bilim University Faculty of Medicine, Department of Pediatric Surgery between January 2005 and February 2025. A total of 1,039 children (499 males, 540 females; mean age: 4.7±3.1 years; range, 4 days and 17 years) with the diagnosis of spina bifida and spina bifida occulta who were under follow-up within the last 20 years were included in the study. Medical data were retrieved from the hospital records. Inclusion criteria were as follows: having a diagnosis of either occult or apert spina bifida, any renal anomaly detected with either urinary ultrasonography or static scintigraphy including rotation, fusion, developmental and positional anomalies. The imaging methods used in the follow up of our patients were ultrasonography, voiding cystourethrography (VCUG), when needed, and dimercaptosuccinic acid (DMSA) scintigraphy. Routine radiological follow up of the patients was yearly ultrasonographic screening and VCUG, when needed, and at least two DMSA scintigraphy scans in the first five years of life. If a consistent diagnosis of any congenital renal anomaly in all these imaging methods was seen, then, the patient was accepted to have this condition. Patients with the diagnosis vesicoureteral reflux (VUR) and hydronephrosis not associated with the congenital renal anomaly were excluded, as these pathologies might not be regarded as congenital but secondary to the effects of NBD. Genital anomalies were also excluded, as these malformations have different developmental origin than mesodermal defects. These data were evaluated with the past information in the literature. Age and sex of the patients were also recorded. A comprehensive literature search was carried out. The databases searched during the study were PubMed, Scopus, Embase and Cochrane Library with the keywords of spina bifida, spinal dysraphism, renal, kidney, renal failure, VUR, reflux, urinary bladder, urodynamics, urology, congenital anomaly, malformation, abnormality, spine. All the English references were collected from these databases. All the reports, case series or case reports were searched to identify the association of congenital renal anomalies with spina bifida. Data were gathered and summarized. Frequencies and percentages of the anomalies were calculated, including the side of the renal anomaly and sex difference in each anomaly. Written informed consent was obtained from the parents and/or legal guardians of the patients. The study protocol was approved by the İstanbul Medeniyet University Göztepe Training and Research Hospital Clinical Research Ethics Committee (Date: 02.12.2020, No: 2020/0618). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Statistical analysis

The data were expressed and given in case numbers, frequency and percentages. The mean ages were given in mean ± standard deviation (SD).

Results

Of a total of 1,039 patients, 127 had unilateral hydronephrosis and 40 had bilateral hydronephrosis. There were 135 right-sided and 72 left-sided hydronephrosis in terms of the side of the pathology.

Seventeen patients had some form of rotational anomaly: 10 on the right side and seven on the left. Of these, 12 were male and five were female. Thirteen patients had the diagnosis of horse-shoe kidney (six boys, seven girls). Nine patients had renal agenesis: four had right-sided and five had left-sided agenesis. Of these, five were male and four were female. Three patients had cross-renal ectopia and one had ureterocele and one had ureteropelvic junction obstruction. The total number of patients with congenital renal anomalies associating with spina bifida was found to be 44 with a prevalence of 4.23% in this cohort.

The patients reported in the English literature to date, combined with this study findings, are summarized in Table 1.

Table 1. Literature review of congenital anomalies of kidney and urinary tract

Table 1. Continued

Discussion

The embryogenesis of the urinary tract is intricately linked to the development of the vertebral column. Vertebral somites develop from paraxial mesoderm and pronephros develop from intermediate mesoderm. These two mesodermal tissues lie adjacent to each other during embryogenesis.[1] During early gestation, the formation of the pronephros, mesonephros, and ultimately the metanephros, which becomes the definitive kidney, occurs in a tightly regulated sequence. Disruptions in these processes, which may accompany neural tube defects, can result in anomalies such as renal dysplasia or unilateral renal agenesis.[2] Aberrations in the formation or branching of the ureteric bud may lead to duplications or ectopic positioning of the collecting system, further complicating the clinical picture. These anomalies not only affect renal function, but also influence the dynamics of the lower urinary tract, setting the stage for secondary complications such as VUR and recurrent urinary tract infections (UTIs). Early identification is crucial, as congenital anomalies, if unrecognized, can predispose patients to long-term complications including VUR, UTIs, and progressive renal scarring, which may eventually compromise renal function.[5]

Bladder is embryologically, urogenital sinus in origin and its functions are in neurological control. This control is compromised in patients with spina bifida due to the primary and secondary neurological injury. Loss of synergistic activity of detrusor and urinary sphincter causes urinary tract deterioration in as much as 71% of newborns within the first three years of life.[36] The presence of congenital urinary anomalies in spina bifida patients carries additional significant clinical ramifications. Renal dysplasia and unilateral renal agenesis may reduce the overall renal reserve, rendering patients more vulnerable to the effects of NBD. In a retrospective analysis of 312 children with spina bifida, 72 of these patients (23%) were found to have renal scarring in their follow up. Additionally, late referral, female sex, NBD with detrusor overactivity and detrusor sphincter dyssynergia were observed to significantly affect renal impairment in this study.[37] Therefore, early and accurate diagnosis is paramount in mitigating the progression toward chronic kidney disease in these patients.

Currently, the prevalence of CAKUT associating with spina bifida is largely unknown. According to our literature search, this ratio seems to be between 2 and 17.8%.[3,6-9] In this current study, among 1,039 children with spina bifida, 44 of them were found to have a form of CAKUT with a prevalence rate of 4.23%. The only study that comprised 1,170 patients was from a multi-national, multi-centric, long-term database study and this prevalence was 3.59% in the same patient group. Therefore, our study seems to have the largest single center case series in the literature on this subject. Still, when we consider the general incidence of CAKUT of 4 to 60/10,000 live births, it is plausible to speculate that this ratio is extremely high in cases of spina bifida. In a clinical study including 231 patients with congenital scoliosis, the incidence of urological anomalies was found to be 18%.[38] This raises the possibility of a genetic background for renal anomalies in patients with congenital spinal pathologies. However, although the role of genetics in organ development is well established, the interplay between genetic and environmental factors is still accepted to be responsible for CAKUT.[4] Among these environmental factors, maternal obesity, diabetes mellitus and folic acid deficiency were also accused for the development of CAKUT.[4,39] This issue is critical, as these factors are also accepted to be responsible for the development of neural tube defects. In their study, Hernandez-Diaz et al.[39] showed that folic acid antagonists taken during pregnancy increased the risk of not only neural tube defects, but also cardiovascular defects, oral clefts and urinary tract defects. This point may give us a reasonable explanation of the association with spina bifida and CAKUT which needs further clarification with detailed clinical studies.

Given the progressive nature of many congenital urinary anomalies, long-term follow-up is essential. Regular monitoring through renal ultrasonography, VCUG, and nuclear imaging modalities such as DMSA scintigraphy allows for the early detection of changes in renal structure and function. Such surveillance is critical in identifying evolving complications such as worsening reflux or increasing renal scarring. Ongoing follow-up also provides an opportunity for timely intervention, which is crucial in preserving renal function and maintaining quality of life. Furthermore, the integration of emerging biomarkers and molecular diagnostics may, in the future, refine risk stratification and guide more personalized therapeutic approaches.

Nonetheless, this study has some limitations. First, it has a single-center, cross-sectional, observational, retrospective design and there is no control group to test the hypotheses for the association of these two groups of anomalies. However, it seems to be the largest single-center case series of spina bifida patients in the literature and the literature review of all the case series may serve as a reference for further studies on this subject. Second, the diagnosis of renal anomalies was made based on ultrasonography and DMSA scintigraphy which may have potential for diagnostic bias; i.e., some anomalies might have been missed with imaging studies. Third, we did not include the patients with VUR to the patient group, as it is difficult to understand if the reflux is primary or secondary under the circumstances of NBD. The numbers of patients with hydroureteronephrosis may show the high association of VUR with spina bifida and also the bladder dysfunction related with spina bifida by its own. However, we did not use these criteria for the impossibility of differentiating the congenital or acquired forms of VUR in these patients. Further multi-center, large-scale, prospective studies are warranted to confirm these findings.

In conclusion, CAKUT in spina bifida represent a multifaceted clinical challenge that extends beyond the primary neural tube defect. The prevalence of CAKUT seems to be increased in patients with spina bifida compared to general population. The interplay between embryological disruption, genetic predisposition, and other factors may result in a spectrum of urinary tract malformations that has potential impact on renal function and quality of life. Early detection via advanced prenatal imaging, combined with a multidisciplinary management strategy, is critical to mitigate long-term renal damage and improve patient outcomes. Continued research into the molecular mechanisms underlying these anomalies may hold promise for the development of innovative prenatal therapies and more personalized treatment protocols. Ultimately, vigilant post-natal monitoring and comprehensive care remain essential to safeguard renal function and enhance the quality of life for spina bifida patients associated with CAKUT.

Citation: Özel ŞK, Alataş İ, Ay L. The prevalence of congenital anomalies of kidney and urinary tract in children with spina bifida: A cross-sectional study. Turkish J Ped Surg 2025;39(3):103-109. doi: 10.62114/JTAPS.2025.146.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Idea/concept, control/ supervision, data collection and/or processing: Ş.K.Ö., İ.A.; Design, writing the article, materials: Ş.K.Ö.; Literature review, references and funding: Ş.K.Ö., L.A.; Critical review: İ.A., L.A.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

The authors received no financial support for the research and/or authorship of this article.

References

1. Kaplan KM, Spivak JM, Bendo JA. Embryology of the spine and associated congenital abnormalities. Spine J 2005;5:564-76. doi: 10.1016/j.spinee.2004.10.044.
2. Brockwell M, Hergenrother S, Satariano M, Shah R, Raina R. Pathophysiology of congenital anomalies of the kidney and urinary tract: A comprehensive review. Cells 2024;13:1866. doi: 10.3390/cells13221866.
3. Parker SE, Yazdy MM, Mitchell AA, Demmer LA, Werler MM. A description of spina bifida cases and co-occurring malformations, 1976-2011. Am J Med Genet A 2014;164A:432-40. doi: 10.1002/ ajmg.a.36324.
4. Costigan CS, Rosenblum ND. Anatomy and embryology of congenital surgical anomalies: Congenital anomalies of the kidney and urinary tract. Semin Pediatr Surg 2022;31:151232. doi: 10.1016/j.sempedsurg.2022.151232.
5. dos Santos Junior AC, de Miranda DM, Simões e Silva AC. Congenital anomalies of the kidney and urinary tract: An embryogenetic review. Birth Defects Res C Embryo Today 2014;102:374-81. doi: 10.1002/bdrc.21084.
6. Roberts JB. Congenital anomalies of the urinary tract and their association with spina bifida. Br J Urol 1961;33:309-15. doi: 10.1111/j.1464-410x.1961.tb11621.x.
7. Bamforth SJ, Baird PA. Spina bifida and hydrocephalus: A population study over a 35-year period. Am J Hum Genet 1989;44:225-32.
8. Fernbach SK, Davis TM. The abnormal renal axis in children with spina bifida and gibbus deformity--the pseudohorseshoe kidney. J Urol 1986;136:1258-60. doi: 10.1016/s0022-5347(17)45307-9.
9. Öztürk PA, Öztürk Ü, Tamam Y. Nöral tüp defektli hastalarda tek taraflı renal agenezi/displazi. Çukurova Medical Journal 2019;44:1546-1548.
10. Smith DE. Spina bifida and the total care of spinal myelomeningocele, Springfield: Charles C Thomas; 1965.
11. Tori JA, Dickson JH. Association of congenital anomalies of the spine and kidneys. Clin Orthop Relat Res 1980;(148):259-62.
12. Whitaker RH, Hunt GM. Incidence and distribution of renal anomalies in patients with neural tube defects. Eur Urol 1987;13:322-3. doi: 10.1159/000472810.
13. Alston SR, Fuller GN, Boyko OB, Goscin SA, DiSclafani A. Ectopic immature renal tissue in a lumbosacral lipoma: Pathologic and radiologic findings. Pediatr Neurosci 1989;15:100-3. doi: 10.1159/000120451.
14. Hulton SA, Thomson PD, Milner LS, Isdale JM, Ling J. The pattern of congenital renal anomalies associated with neural tube defects. Pediatr Nephrol 1990;4:491-2. doi: 10.1007/BF00869827.
15. Mandell GA, Maloney K, Sherman NH, Filmer B. The renal axes in spina bifida: Issues of confusion and fusion. Abdom Imaging 1996;21:541-5. doi: 10.1007/s002619900122.
16. Johnston LB, Borzyskowski M. Bladder dysfunction and neurological disability at presentation in closed spina bifida. Arch Dis Child 1998;79:33-8. doi: 10.1136/adc.79.1.33.
17. Nallegowda M, Singh U, Shivananda, Shukla R, Kabra M. A case of dextrocardia, radial ray malformation and renal anomaly. Clin Dysmorphol 2003;12:285-6. doi: 10.1097/00019605-200310000- 00017.
18. Uzüm N, Dursun A, Baykaner K, Kurt G. Split-cord malformation and tethered cord associated with immature teratoma. Childs Nerv Syst 2005;21:77-80. doi: 10.1007/s00381-004-0951-1.
19. Patel CD, Chawla M, Nadig MR, Mahapatra AK, Bal C. Evaluation of dysfunction and malformations of the urinary tract in patients with meningomyelocele, by renal dynamic scintigraphy and direct radionuclide cystography. An Indian perspective. Hell J Nucl Med 2007;10:102-4.
20. Baradaran N, Ahmadi H, Nejat F, El Khashab M, Mahdavi A. Nonneural congenital abnormalities concurring with myelomeningocele: Report of 17 cases and review of current theories. Pediatr Neurosurg 2008;44:353-9. doi: 10.1159/000149900.
21. Kari JA, Safdar O, Jamjoom R, Anshasi W. Renal involvement in children with spina bifida. Saudi J Kidney Dis Transpl 2009;20:102-5.
22. Thakur SK, Gupta S, Gupta SR, Jha S. Reverse rotation of kidney with spina bifida in an adult. Saudi J Kidney Dis Transpl 2010;21:1149-50.
23. Torre M, Guida E, Bisio G, Scarsi P, Piatelli G, Cama A, et al. Risk factors for renal function impairment in a series of 502 patients born with spinal dysraphisms. J Pediatr Urol 2011;7:39-43. doi: 10.1016/j.jpurol.2010.02.210.
24. Patiatil M, Aditya PN, Savale SL. Diastematomyelia with spina bifida occulta and bilateral intrathoracic kidneys. J Clin of Diagn Res 2012;6:923-925.
25. Steelman CK, Bannister LL, Palmer M, Chang TS, Elawabdeh N, Shehata BM. Nephrogenic rest within a lipomyelomeningocele in a patient with unilateral renal agenesis. Fetal Pediatr Pathol 2012;31:260-4. doi: 10.3109/15513815.2012.659377.
26. Calleja Aguayo E, Estors Sastre B, Bragagnini Rodríguez P, Fustero de Miguel D, Martínez-Pardo NG, Eliás Pollina J. Currarino triad: Different forms of presentation. Cir Pediatr 2012;25:155-8.
27. Aydin H, Yoldaş M., Yeşiller E, Geckinli B, Karaman A, Tuğ E, et al. Two cases of spina bifida and renal anomaly with differing findings. South Clin Ist Euras 2015;26:272-276. doi: 10.5505/ jkartaltr.2014.52385.
28. Bozdogan E, Demir M, Konukoglu O, Karakas E. Reverse U-shaped horseshoe kidney accompanied by gibbus deformity and spina bifida. Jpn J Radiol 2016;34:448-50. doi: 10.1007/s11604- 016-0536-4.
29. Parmar J, Mohan C, Vora M. Cephalad-renal ectopia: Bilateral subdiaphragmatic kidneys in a patient of omphalocele with ventral hernia. Ped Urol Case Rep 2016;3:63-67.
30. Özgönenel E, Karalök I, Günay EC, Duymaz T, Alataş I, Özvar MB, et al. Comparison between Tc-99m DMSA and renal ultrasonography for the evaluation of renal scarring and function loss in children with spina bifida. İstanbul Med J 2017;18:76-9. doi: 10.5152/imj.2017.67625.
31. Maeda H, Go H, Sakuma J, Imamura T, Sato M, Momoi N, et al. Myelomeningocele with unilateral right renal agenesis: A case report. AJP Rep 2018;8:e1-3. doi: 10.1055/s-0037- 1615818.
32. Kaur A, Sharma M. Spina bifida- a retrospective study. Int J Anat Res 2019;7:6390-96. doi: 10.16965/ijar.2019.124.
33. Puvabanditsin S, Negroponte E, Jang P, Hedges A, Kased R, Mehta R. Multiple congenital anomalies in a patient with ınterstitial 6q26 deletion. Mol Syndromol 2020;10:276-80. doi: 10.1159/000503698.
34. Mazzone L, Hölscher AC, Moehrlen U, Gobet R, Meuli M, Horst M. Urological outcome after fetal spina bifida repair: Data from the Zurich Cohort. Fetal Diagn Ther 2020;47:882-8. doi: 10.1159/000509392.
35. Hong ZH, Jin DH, Yuan XJ, Zhao Y, Lin HW, Chen J. Association of neural tube defects with congenital abnormalities of the urogenital system in a Chinese cohort. BMC Pediatr 2021;21:66. doi: 10.1186/s12887-021-02492-8.
36. Johnson EK, Bauer SB. Neurogenic voiding dysfunction and functional voiding disorders: evaluation and nonsurgical management. In: Docimo SG, Austin P, Canning D, Coplen DE, Khoury A, Copp H, editors. The kelalis-king-belman textbook of clinical pediatric urology. 6th ed. London: CRC Press; 2018. p. 820-52.
37. Ozel SK, Dokumcu Z, Akyildiz C, Avanoglu A, Ulman I. Factors affecting renal scar development in children with spina bifida. Urol Int 2007;79:133-6. doi: 10.1159/000106326.
38. MacEwen GD, Winter RB, Hardy JH. Evaluation of kidney anomalies in congenital scoliosis. J Bone Joint Surg Am 1972;54:1451-4.
39. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343:1608-14. doi: 10.1056/ NEJM200011303432204.