Serum Soluble Urokinase Plasminogen Activator Receptor as a Prognostic Biomarker in Children with Chronic Kidney Disease Due to Congenital Anomalies of the Kidney and Urinary System

Öz

Introduction: This study aimed to evaluate the relationship between serum soluble urokinase plasminogen activator receptor (suPAR) levels and chronic kidney disease (CKD) stages in children with CAKUT, the leading cause of pediatric CKD. Metarials and Methods: Forty-two children with CAKUT-related CKD and 42 healthy controls were prospectively enrolled. Serum suPAR levels, estimated glomerular filtration rate (eGFR), and other laboratory parameters were compared. ROC analysis was used to assess the diagnostic performance of suPAR. Results: suPAR levels were significantly higher in the patient group (p<0.001) and increased with CKD severity. A suPAR cut-off of ≥3.38 ng/mL predicted CKD with 85.7% sensitivity and 78.6% specificity. suPAR showed a negative correlation with eGFR and a positive correlation with creatinine and potassium levels. Conclusion: Elevated suPAR levels may reflect CKD progression in children with CAKUT and serve as a non-invasive biomarker for early detection and disease monitoring.

Anahtar Kelimeler

• Soluble Urokinase Plasminogen Activator Receptor (suPAR)
• Chronic Kidney Disease (CKD)
• Congenital Kidney and Urinary System Anomalies (CAKUT)
• Child
• Estimated Glomerular Filtration Rate (eGFR)

Konjenital Böbrek ve Üriner Sistem Anomalilerine bağlı Kronik Böbrek Hastalığı olan Çocuklarda Prognostik Biyobelirteç olarak Serum Çözünür Ürokinaz Plazminojen Aktivatör Reseptörü

Öz

Giriş: Bu çalışmanın amacı, çocuklarda kronik böbrek hastalığının (KBH) en yaygın nedeni olan konjenital böbrek ve üriner sistem anomalileri (CAKUT) bulunan çocuklarda serum suPAR düzeyleri ile KBH evreleri arasındaki ilişkiyi değerlendirmektir. Gereç ve Yöntem: CAKUT kaynaklı KBH tanısı alan 42 çocuk hasta ve 42 sağlıklı kontrol prospektif olarak çalışmaya dahil edildi. Serum suPAR düzeyleri, tahmini glomerüler filtrasyon hızı (eGFR) ve diğer laboratuvar parametreleri karşılaştırıldı. suPAR’ın tanısal değerini belirlemek amacıyla ROC analizi yapıldı. Sonuç: suPAR düzeyleri hasta grubunda anlamlı olarak yüksekti (p<0,001) ve KBH evresi ilerledikçe arttı. 3,38 ng/mL ve üzeri suPAR değerleri, KBH tanısını %85,7 duyarlılık ve %78,6 özgüllük ile öngördü. suPAR ile eGFR arasında negatif, kreatinin ve potasyum düzeyleri ile pozitif korelasyon saptandı. Tartışma: Yükselmiş suPAR düzeyleri, CAKUT’a bağlı KBH ilerlemesini yansıtabilir ve bu biyobelirteç, hastalığın erken tanısı ve takibinde kullanılabilecek non-invaziv bir yöntem olabilir.

Anahtar Kelimeler

• Çözünür Ürokinaz Plazminojen Aktivatör Reseptörü (suPAR)
• Kronik Böbrek Hastalığı (KBH)
• Konjenital Böbrek ve Üriner Sistem Anomalileri (CAKUT)
• Çocuk
• Tahmini Glomerüler Filtrasyon Hızı (eGFR)

Kaynakça

1. 1.Lameire NH, Levin A, Kellum JA, Cheung M, Jadoul M, Winkelmayer WC, Stevens PE; Conference Participants. Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference. Kidney Int. 2021 Sep;100(3):516-526. Epub 2021 Jul 9. PMID: 34252450 [Crossref]
2. 2.Harambat, J., van Stralen, K. J., Kim, J. J., & Tizard, E. J. Epidemiology of chronic kidney disease in children. Pediatric nephrology (Berlin, Germany). 2012;27(3):363-373. [Crossref]
3. 3.Bek, K., Akman, S., Bilge, I., Topaloğlu, R., Calişkan, S., Peru, H., Cengiz, N., & Söylemezoğlu, O. Chronic kidney disease in children in Turkey. Pediatric nephrology (Berlin, Germany). 2009;24(4):797-806. [Crossref]
4. 4.Wiesel, A., Queisser-Luft, A., Clementi, M., Bianca, S., Stoll, C., & EUROSCAN Study Group. Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709,030 births in 12 European countries. European journal of medical genetics. 2005;48(2):131-144. [Crossref]
5. 5.Schedl A. Renal abnormalities and their developmental origin. Nature reviews. Genetics. 2007;8(10):791-802. [Crossref]
6. 6.Huai Q, Mazar AP, Kuo A, et al. Structure of human urokinase plasminogen activator in complex with its receptor. Science. 2006;311(5761):656-659. [Crossref]
7. 7.Wei C, Möller CC, Altintas MM, et al. Modification of kidney barrier function by the urokinase receptor. Nat Med. 2008;14(1):55-63. [Crossref]
8. 8.Zeier M, Reiser J. suPAR and chronic kidney disease-a podocyte story. Pflugers Arch. 2017;469(7-8):1017-1020. [Crossref]

9. 9.Garofolo M, Vitale M, Penno G, et al. Prognostic impact of switching to the 2021 chronic kidney disease epidemiology collaboration creatinine-based equation in Caucasian patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular events (RIACE) Italian Multicenter Study. Cardiovasc Diabetol. 2024;23(1):377. Published 2024 Oct 24. [Crossref]
10. 10.Wei C, Möller CC, Altintas MM, et al. Modification of kidney barrier function by the urokinase receptor. Nat Med. 2008;14(1):55-63. [Crossref]
11. 11.Zeier M, Reiser J. suPAR and chronic kidney disease-a podocyte story. Pflugers Arch. 2017;469(7-8):1017-1020. [Crossref]
12. 12.Kronbichler A, Saleem MA, Meijers B, Shin JI. Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View. J Immunol Res. 2016;2016:2068691. [Crossref]
13. 13.Hayek SS, Sever S, Ko YA, et al. Soluble Urokinase Receptor and Chronic Kidney Disease. N Engl J Med. 2015;373(20):1916-1925. [Crossref]
14. 14.Schulz CA, Persson M, Christensson A, et al. Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) and Impaired Kidney Function in the Population-based Malmö Diet and Cancer Study. Kidney Int Rep. 2017;2(2):239-247. [Crossref]
15. 15.Alfano M, Cinque P, Giusti G, et al. Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes. Sci Rep. 2015;5:13647. Published 2015 Sep 18. [Crossref]
16. 16.Maas RJH, Wetzels JFM, Deegens JKJ. Serum-soluble urokinase receptor concentration in primary FSGS. Kidney Int. 2012;81(10):1043-1044. [Crossref]
17. 17.Wei C, El Hindi S, Li J, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med. 2011;17(8):952-960. Published 2011 Jul 31. [Crossref]
18. 18.Sharma M, Sharma R, Reddy SR, McCarthy ET, Savin VJ. Proteinuria after injection of human focal segmental glomerulosclerosis factor. Transplantation. 2002;73(3):366-372. [Crossref]
19. 19.Weidemann DK, Abraham AG, Roem JL, Furth SL, Warady BA. Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) and CKD Progression in Children. Am J Kidney Dis. 2020;76(2):194-202. [Crossref]
20. 20.Schaefer F, Trachtman H, Wühl E, et al. Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children. JAMA Pediatr. 2017;171(11):e172914. [Crossref]