Stratification of kidney damage severity in children with vesicoureteral reflux based on cluster analysis of imaging data

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Abstract

BACKGROUND: Vesicoureteral reflux is one of the most important risk factors for the development of urinary tract infections in children, leading to renal parenchymal injury. Assessment of the severity of vesicoureteral reflux based on imaging modalities does not always correlate with the reflux grade, which complicates the selection of patient management strategies.

AIM: The work aimed to evaluate the feasibility of using cluster analysis for stratification of the degree of structural and kidney function damage in children with vesicoureteral reflux based on imaging data.

METHODS: The study included 101 patients (143 renal units) aged 1 month to 7 years. Renal imaging methods were used, including Doppler ultrasound, static renal scintigraphy, and excretory urography. Clustering of the diagnostic dataset was performed using the TwoStep cluster method (SPSS Statistics, version 23.0; IBM, USA), which allows for simultaneous analysis of quantitative and qualitative variables. The optimal number of clusters was determined using the silhouette coefficient.

RESULTS: Cluster analysis identified four clusters of renal units (RUs): cluster 1, with no changes in renal structure, hemodynamics, or function (34 RUs); cluster 2, with minor changes and early signs of nephrosclerosis (55 RUs); cluster 3, with moderate impairment (45 RUs); and cluster 4, with pronounced changes in the renal parenchyma (9 RUs). A trend toward an increase in the number of renal units in clusters 3 and 4 with increasing grade of vesicoureteral reflux was observed: at grades 1–2, clusters 1 and 2 predominated; at grade 3, clusters 2 and 3; and at grades 4–5, cluster 4 predominated.

CONCLUSION: Cluster analysis of imaging data enabled stratification of the severity of kidney damage in children with vesicoureteral reflux using a multidimensional analytical approach.

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About the authors

Karmina N. Demidova

I.M. Sechenov First Moscow State Medical University

Author for correspondence.
Email: negmatova.karmina@mail.ru
ORCID iD: 0000-0002-2243-7073
SPIN-code: 9281-4273

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Vera V. Rostovskaya

I.M. Sechenov First Moscow State Medical University; Speransky Children’s Hospital No. 9

Email: rostovskaya_vera@mail.ru
ORCID iD: 0000-0002-3718-8911
SPIN-code: 6989-5041

MD, Dr. Sci. (Medicine)

Russian Federation, Moscow; Moscow

Galina I. Kuzovleva

I.M. Sechenov First Moscow State Medical University; Speransky Children’s Hospital No. 9

Email: dr.gala@mail.ru
ORCID iD: 0000-0002-5957-7037
SPIN-code: 7990-4317

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow; Moscow

Irina E. Starostina

DocMed Evidence-Based Medicine Clinic

Email: irinamadness1@gmail.com
ORCID iD: 0000-0002-3251-6904
Russian Federation, Moscow

References

  1. Gnech M, ‘t Hoen L, Zachou A, et al. Update and summary of the European Association of Urology/European Society of Paediatric Urology paediatric guidelines on vesicoureteral reflux in children. Eur Urol. 2024;85(5):433–442. doi: 10.1016/j.eururo.2023.12.005
  2. Morozova OL, Lakomova DY, Zakharova NB, et al. Reflux nephropathy in children: pathogenesis and prognosis. Part 1. Urologiia. 2021;(3):150–154. doi: 10.18565/urology.2021.3.150-154 EDN: BKXWTV
  3. Andrioli V, Regacini R, Aguiar W. Primary Vesicoureteral reflux and chronic kidney disease in pediatric population. What we have learnt? Int Braz J Urol. 2020;46(2):262–268. doi: 10.1590/S1677-5538.IBJU.2020.02.02
  4. Hewitt I, Montini G. Vesicoureteral reflux is it important to find? Pediatr Nephrol. 2021;36(4):1011–1017. doi: 10.1007/s00467-020-04573-9
  5. Aboutaleb H, Abouelgreed TA, El-Hagrasi H, et al. Correlation of renal scarring to urinary tract infections and vesicoureteral reflux in children. Adv Urol. 2022:9697931. doi: 10.1155/2022/9697931
  6. Woo LL. “Bottoms Up!”: A Toast to reexamining the debate of top-down vs bottom-up approach for the evaluation of febrile urinary tract infection. J Urol. 2021;206(5):1095–1096. doi: 10.1097/JU.0000000000002171
  7. Simičić Majce A, Arapović A, Čapkun V, et al. The spectrum of parenchymal changes in kidneys affected by intrarenal reflux, diagnosed by contrast-enhanced voiding urosonography and DMSA scan. Front Pediatr. 2022;10:886112. doi: 10.3389/fped.2022.886112
  8. Pavlov AY, Sabirzyanova ZR. Clinical interpretation of the results of radionuclide research methods in the evaluation of diseases of the urinary system in children (lecture). Bashkortostan Medical Journal. 2023;18(1):103–108. EDN: FEHSLN
  9. Läckgren G, Cooper CS, Neveus T, Kirsch AJ. Management of vesicoureteral reflux: what have we learned over the last 20 years? Front Pediatr. 2021;9:650326. doi: 10.3389/fped.2021.650326
  10. Marzuillo P, La Manna A, Palma PL, et al. Voiding cystourethrography for the pediatric nephrologist: clinical value, challenges, and areas of debate. Pediatr Nephrol. 2025;41:1278–1301. doi: 10.1007/s00467-025-06901-3
  11. Morozova OL, Lakomova DY, Zakharova NB, et al. Reflux nephropathy in children: pathogenesis and prognosis. Part 2. Urologiia. 2021;(4):145–151. doi: 10.18565/urology.2021.4.145-151 EDN: KBLOVE
  12. Valério FC, Lemos RD, de C Reis AL, et al. Biomarkers in vesicoureteral reflux: an overview. Biomark Med. 2020;14(8):683–696. doi: 10.2217/bmm-2019-0378
  13. Mirkin BG. Cluster analysis methods for decision support: A review. Moscow: Publishing House of the National Research University “HSE”; 2011. 84 p. EDN: QUSUXH (In Russ.)
  14. Alsova OK. Algorithms for clustering of a heterogeneous data on the example of solution of the medical task. In: SPIIRAS proceedings. Vol. 37. Saint Petersburg, 2014. P. 156–169. EDN: TELOKB
  15. Lee J, Warner E, Shaikhouni S, et al. Clustering-based spatial analysis (CluSA) framework through graph neural network for chronic kidney disease prediction using histopathology images. Sci Rep. 2023;13:12701. doi: 10.1038/s41598-023-39591-8
  16. Saito H, Yoshimura H, Tanaka K, et al. Predicting CKD progression using time series clustering and light gradient boosting machines. Sci Rep. 2024;14(1):1723. doi: 10.1038/s41598-024-52251-9
  17. Cummins T, Merchant М, Rane M, et al. Urine biomarker analysis of pediatric nephrotic syndrome: FR-PO661. J Am Soc Nephrol. 2023;34(11S):584. doi: 10.1681/ASN.20233411S1584c
  18. Sherman MA, Gunawardana A, Amirault JP, et al. Autoantibody cluster analysis in juvenile lupus nephritis. Clin Rheumatol. 2022;41(8):2375–2381. doi: 10.1007/s10067-022-06146-7
  19. Schneider AJ, Grimes M, Lyon W, et al. Cluster analysis of men undergoing surgery for BPH/LUTS reveals prominent roles of both bladder outlet obstruction and diminished bladder contractility. PLoS ONE. 2021;16(5):0251721. doi: 10.1371/journal.pone.0251721
  20. Andreev VP, Helmuth ME, Liu G, et al. Subtyping of common complex diseases and disorders by integrating heterogeneous data. Identifying clusters among women with lower urinary tract symptoms in the LURN study. PLoS One. 2022;17(6):0268547. doi: 10.1371/journal.pone.0268547
  21. Nithya А, Appadurai А, Venkatadri N, et al. Кidney disease detection and segmentation using artificial neural network and multi-kernel k-means clustering for ultrasound images. Measurement. 2020;149:106952. doi: 10.1016/j.2019.106952
  22. Chiglintsev KA, Zyryanov AV, Chiglintsev AYu. Cluster analysis of the main parameters of homeostasis with kidney injury. Urologiia. 2021;(4):25–29. doi: 10.18565/urology.2021.4.25-29 EDN: ACJPLA
  23. Тzelves L, Feretzakis G, Kalles D, et al. Cluster analysis assessment in proposing a surgical technique for benign prostatic enlargement. Stud Health Technol Inform. 2022;295:466–469. doi: 10.3233/SHTI220766
  24. Fazelinia H, Ding H, Taylor D, et al. Stratification of neurogenic bladder risk in spina bifida using the urinary peptidome. Am J Physiol Renal Physiol. 2024;326(2):241–248. doi: 10.1152/ajprenal.00267.2023
  25. De Ruysscher C, Pien L, Tailly T, et al. Risk factors for recurrent urolithiasis in children. J Pediatr Urol. 2020;16(1):34.e1–34.e9. doi: 10.1016/j.jpurol.2019.09.021
  26. Fernandez N, Maxwell A, Noonavath M, Shnorhavoriana M. Comprehensive multidisciplinary phenotyping of patients with hypospadias. A pilot study. J Pediatr Urol. 2023;19(4):397.e1–397.e7. doi: 10.1016/j.jpurol.2023.04.005
  27. Patent RU No. 2270605/ 27.02.2006. Yatsyk SP, Zubovsky GA, Fomin DK. A method for assessing the viability of renal parenchyma. (In Russ.)
  28. Bacher J, Wenzig K, Vogler M. SPSS TwoStep cluster — a first evaluation. University Erlangen-Nürnberg: Lehrstuhl für Soziologie; 2004.
  29. Kent P, Jensen RK, Kongsted A. A comparison of three clustering methods for finding subgroups in MRI, SMS or clinical data: SPSS TwoStep cluster analysis, latent gold and SNOB. BMC Med Res Methodol. 2014;14:113. doi: 10.3386/1471-2288-14-113
  30. Costea RM, Maniu I, Dobrota L, et al. Exploring inflammatory status in febrile seizures associated with urinary tract infections: A two-step cluster approach. Brain Sci. 2021;11(9):1168. doi: 10.3390/brainsci11091168
  31. Preda I, Jodal U, Sixt R, et al. Normal dimercaptosuccinic acid scintigraphy makes voiding cystourethrography unnecessary after urinary tract infection. J Pediatr. 2007;151(6):581–584. doi: 10.1016/j.jpeds.2007.05.008
  32. Herz DB. The top-down approach: an expanded methodology. J Urol. 2010;183(3):856–857. doi: 10.1016/j.juro.2009.12.062

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Silhouette analysis of clustering quality of renal units at K = 4. The dashed line indicates the silhouette coefficient (s = 0.54).

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