Advances in biomarker-based assessment of kidney injury in pediatric nephrotic syndrome: A narrative review

  • Heorhii Liezhentsev Bogomolets National Medical University, Kyiv, Ukraine https://orcid.org/0009-0006-3572-0229
  • Ievgeniia Burlaka Bogomolets National Medical University, Kyiv, Ukraine https://orcid.org/0000-0001-6043-7325
  • Ingretta Bagdasarova State Institution “O.O. Shalimov National Scientific Centre for Surgery and Transplantology of the National Academy of Medical Sciences of Ukraine,” Kyiv, Ukraine; International Centre for Astronomical, Medical and Ecological Research, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • Olena Zakrarycheva State Institution “O.O. Shalimov National Scientific Centre for Surgery and Transplantology of the National Academy of Medical Sciences of Ukraine,” Kyiv, Ukraine
Keywords: pediatric nephrotic syndrome, biomarkers, risk stratification, diagnostic challenges, children

Abstract

Pediatric nephrotic syndrome (NS) presents significant diagnostic and prognostic challenges in contemporary clinical practice. Despite advances in understanding disease mechanisms, substantial gaps persist in risk stratification frameworks, standardized diagnostic criteria for complex cases, and clinical implementation of novel biomarkers.

The present review aimed to critically evaluate current and emerging diagnostic approaches for detecting early kidney injuries in pediatric nephrotic syndrome, examining developmental renal physiology, disease mechanisms, conventional marker limitations, novel biomarkers and multi-marker strategies to provide evidence-based recommendations for improving early detection and long-term outcomes in affected children.

The review summarizes current evidence on the clinical relevance of novel biomarkers of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid–binding protein (L-FABP), N-acetyl-β-D-glucosaminidase, cystatin C, interleukin-18, and osteopontin. These biomarkers reflect different pathophysiological mechanisms such as tubular injury, inflammation, ischemia, oxidative stress, fibrosis and are able to detect subclinical renal damage before a measurable decline in glomerular filtration rate occurs. Particular attention is given to KIM-1, NGAL, and L-FABP as early indicators of tubular injury, as well as to osteopontin as a marker associated with chronic inflammation and renal fibrotic remodeling. Available data indicate that the combined use of several biomarkers improves early detection, risk stratification and monitoring of disease course in children with nephrotic syndrome.

Downloads

Download data is not yet available.

References

Chan EY, Boyer O. Childhood idiopathic nephrotic syndrome: Recent advancements shaping future guidelines. Pediatr Nephrol. 2025;40(8):2431-2442. doi: 10.1007/s00467-024-06634-9.

Vivarelli M, Gibson K, Sinha A, Boyer O. Childhood nephrotic syndrome. Lancet. 2023;402(10404):809-824. doi: 10.1016/S0140-6736(23)01051-6.

Lee JM, Ahn YH, Lim SH, Kang H G. Biomarkers Predicting Treatment-Response in Nephrotic Syndrome of Children: A Systematic Review. Childhood Kidney Diseases. 2021;25(2):92-111. doi: 10.3339/jkspn.2021.25.2.92.

Wendt R, Sobhani A, Diefenhardt P, Trappe M, Völker LA. An updated comprehensive review on diseases associated with nephrotic syndromes. Biomedicines. 2024;12(10):2259. doi: 10.3390/biomedicines12102259.

Frățilă VG, Lupușoru G, Sorohan BM, Obrișcă B, Mocanu V, Lupușoru M, Ismail G. Nephrotic syndrome: From pathophysiology to novel therapeutic approaches. Biomedicines. 2024;12(3):569. doi: 10.3390/biomedicines12030569.

Bogdanović L, Babić I, Prvanović M, Mijač D, Mladenović-Marković A, Popović D, Bogdanović J. Uncommon factors leading to nephrotic syndrome. Biomedicines. 2025;13(8):1907. doi: 10.3390/biomedicines13081907.

Ponticelli C, Moroni G. Nephrotic syndrome: pathophysiology and consequences. J Nephrol. 2023;36(8):2179-2190. doi: 10.1007/s40620-023-01697-7. Erratum in: J Nephrol. 2025;38(7):2025. doi: 10.1007/s40620-025-02400-8.

Lousa I, Reis F, Beirão I, Alves R, Belo L, Santos-Silva A. New potential biomarkers for chronic kidney disease management: A review of the literature. Int J Mol Sci. 2021;22(1):43. doi: 10.3390/ijms22010043.

Jacob M, Nimer RM, Alabdaljabar MS, Sabi EM, Al-Ansari MM, Housien M, et al. Metabolomics profiling of nephrotic syndrome towards biomarker discovery. Int J Mol Sci. 2022;23(20):12614. doi: 10.3390/ijms232012614.

Zhu Y, Chen J, Zhang Y, Wang X, Wang J. Immunosuppressive agents for frequently relapsing/steroid-dependent nephrotic syndrome in children: A systematic review and network meta-analysis. Front Immunol. 2024;15:1310032. doi: 10.3389/fimmu.2024.1310032.

Tkaczyk M, Nowicki M, Lukamowicz J. Increased cystatin C concentration in urine of nephrotic children. Pediatr Nephrol. 2004;19(11):1278-80. doi: 10.1007/s00467-004-1566-1.

Skidmore M, Spencer S, Desborough R, Kent D, Bhandari S. Cystatin C as a Marker of Kidney Function in Children. Biomolecules. 2024;14(8):938. doi: 10.3390/biom14080938.

Abdalla A, Ali A, Abufatima IO, Majzoub S, Elbasheer TAE, Ahmed SMAO, et al. Use of urinary NGAL in steroid-resistant vs. steroid-sensitive nephrotic syndrome: a systematic review and meta-analysis. BMC Nephrol.2025;26(1):486. doi: 10.1186/s12882-025-04420-9.

Zhang Y, Xiang C, Gong L, Zhang Y, Zhen J, Hu Z, Xiao X. Kidney injury molecule-1 levels are associated with therapeutic outcomes and renal tubulointerstitial injury severity in idiopathic membranous nephropathy. Exp Ther Med. 2021;22(6):1434. doi: 10.3892/etm.2021.10869.

Welliam Y, Witarto BS, Visuddho V, Wungu CDK, Budiarto RM, Susilo H. Osteopontin, kidney injury molecule-1, and fetuin-A as prognostic markers of end-stage renal disease: A systematic review and meta-analysis. PLoS One. 2025;20(4):e0320804. doi: 10.1371/journal.pone.0320804.

Tavares MB, Melo CVB, Fernandes PN, Almeida MDCC, Carneiro MFDSM, Santos RFS, et al. Biomarkers of acute kidney injury in patients with nephrotic syndrome. J Bras Nefrol. 2021;43(1):20-27. doi: 10.1590/2175-8239-JBN-2020-0021.

Nishida M, Kawakatsu H, Hamaoka K. Urinary liver-type fatty acid-binding protein in pediatric nephrotic syndrome and tubular dysfunction. Pediatr Int. 2018;60(5):442-445. doi: 10.1111/ped.13533.

Mitsides N, Mitra V, Saha A, Harris S, Kalra PA, Mitra S. Urinary liver-type fatty acid binding protein, a biomarker for disease progression, dialysis and overall mortality in chronic kidney disease. J. Pers. Med.2023;13(10):1481. doi: 10.3390/jpm13101481.

Liu X, Gong S, Ning Y, Li Y, Zhou H, He L, et al. Urinary N-Acetyl-Beta-D-Glucosaminidase levels predict immunoglobulin a nephropathy remission status. BMC Nephrol. 2023;24(1):208. doi: 10.1186/s12882-023-03262-7.

Hirooka Y, Nozaki Y. Interleukin-18 in inflammatory kidney disease. Front Med (Lausanne). 2021;8:639103. doi: 10.3389/fmed.2021.639103.

Piekoszewska-Ziętek P, Korytowska-Przybylska N, Pańczyk-Tomaszewska M, Olczak-Kowalczyk D. Salivary interleukin-6 and interleukin-18 levels and their association with dental health in children with idiopathic nephrotic syndrome. Int. J. Mol. Sci.2025;26(7):3175. doi: 10.3390/ijms26073175.

Sinha SK, Mellody M, Carpio MB, Damoiseaux R, Nicholas SB. Osteopontin as a Biomarker in Chronic Kidney Disease. Biomedicines. 2023;11(5):1356. doi: 10.3390/biomedicines11051356.

Trautmann A, Hofstetter J, Lipska-Ziętkiewicz B, Tsygin A, Ogarek I, Saeed B, et al. Efficacy of Calcineurin Inhibition in Children With Steroid-Resistant Nephrotic Syndrome. Kidney Int Rep. 2025;10(10):3535-3548. doi: 10.1016/j.ekir.2025.07.037.

Burlaka IA, Bagdasarova IV. Molecular factors predicting steroid resistance in pediatric nephrotic syndrome. Ukr J Nephr Dial. 2021;2(70):32–37. doi: 10.31450/ukrjnd.2(70).2021.04.

Barinotti A, Radin M, Cecchi I, Foddai SG, Rubini E, Roccatello D, et al. Serum biomarkers of renal fibrosis: A systematic review. Int. J. Mol. Sci.2022;23(22):14139. doi: 10.3390/ijms232214139.


Abstract views: 186
PDF Downloads: 90
Published
2026-03-08
How to Cite
Liezhentsev, H., Burlaka, I., Bagdasarova, I., & Zakrarycheva, O. (2026). Advances in biomarker-based assessment of kidney injury in pediatric nephrotic syndrome: A narrative review. Ukrainian Journal of Nephrology and Dialysis, (1(89), 66-74. https://doi.org/10.31450/ukrjnd.1(89).2026.08