Indian Journal of Critical Care Medicine

Register      Login

SEARCH WITHIN CONTENT

FIND ARTICLE

Volume / Issue

Online First

Archive
Related articles

VOLUME 28 , ISSUE 10 ( October, 2024 ) > List of Articles

Original Article

Early Diagnostic and Prognostic Value of the Urinary TIMP-2 and IGFBP-7 in Acute Kidney Injury in Critically Ill Children

Mervat Ismail, Nehal Abdelhamid, Hasanin M Hasanin, Hanan M Hamed, Ayat A Motawie, Solaf Kamel, Eman M Hassan, Radwa S Iraqy

Keywords : Acute kidney injury, Critically ill children, Pediatric intensive care unit

Citation Information : Ismail M, Abdelhamid N, Hasanin HM, Hamed HM, Motawie AA, Kamel S, Hassan EM, Iraqy RS. Early Diagnostic and Prognostic Value of the Urinary TIMP-2 and IGFBP-7 in Acute Kidney Injury in Critically Ill Children. Indian J Crit Care Med 2024; 28 (10):970-976.

DOI: 10.5005/jp-journals-10071-24815

License: CC BY-NC 4.0

Published Online: 30-09-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Abstract

Background: Acute kidney injury (AKI) is a hidden complication among children within pediatric intensive care units (PICU). Aim: To evaluate the early predictive and diagnostic value of Urinary [TIMP-2]•[IGFBP7] to detect AKI in PICU patients. Methods: A case-control study was conducted on 112 children (72 admitted to PICU and 40 healthy controls) Urinary [TIMP-2]•[IGFBP7] was measured within 24 hours of PICU admission. Results: Acute kidney injury developed in 52 (72.2%) out of 72 critically ill patients. The AKI group had significantly higher serum creatinine, CRP, and pediatric sequential organ failure assessment score (pSOFA) score (p = 0.001, 0.01, and 0.001, respectively) and significantly lower estimated creatinine clearance (eCCl) (p = 0.001). Urinary [TIMP-2]•[IGFBP7] was significantly higher in the AKI group as compared with the non-AKI group (p = 0.007). The duration of the PICU stay was 1.8-fold higher in the AKI group (p = 0.004). At the time of study enrollment, 7 (13.5%) patients had normal initial eCCl. 26 patients (50.0%) fulfilled the “Risk,” 18 patients (34.6%) the “Injury,” 1 patient (1.9%) the “Failure” and 0 patient (0%) the “Loss” criteria. Nine (17%) patients progressed to the next higher pediatrics risk, injury, failure, loss, end-stage renal disease (pRIFLE) stage. Urinary [TIMP-2]•[IGFBP7] was significantly higher in the “Failure” stage followed by “Injury,” stage then the “Risk,” stage (p = 0.001). Hypovolemia/dehydration had the highest [TIMP-2]•[IGFBP7] values followed by sepsis. Urinary [TIMP-2]•[IGFBP7] was significantly increased in mechanically ventilated and patients who received inotropic medications. Conclusions: [TIMP-2]·[IGFBP7] was higher in AKI patients compared with non-AKI ones especially cases with hypovolemia and sepsis. It may predict severe morbidity and mortality because its higher levels in mechanically ventilated children and those on positive inotropic support.


PDF Share
  1. Banda J, Chenga N, Nambaya S, Bulaya T, Siziya S. Predictors of acute kidney injury and mortality in intensive care unit at a teaching tertiary hospital_ID. Indian J Crit Care Med 2020;24(2):116–121. DOI: 10.5005/jp-journals-10071-23352.
  2. Bhosale SJ, Kulkarni AP. Biomarkers in acute kidney injury. Indian J Crit Care Med 2020;24(Suppl 3):S90–S93. DOI: 10.5005/jp-journals-10071-23398.
  3. KDIGO Clinical Practice Guideline for acute kidney injury: Summary of recommendation statements. Kidney Int Suppl 2012;2(1):19–36. DOI: 10.1038/kisup.2011.32.
  4. Kaddourah A, Basu RK, Goldstein SL, Sutherland SM. Assessment of worldwide acute kidney injury, renal angina and, epidemiology (AWARE) investigators. Oliguria and acute kidney injury in critically ill children: Implications for diagnosis and outcomes. Pediatr Crit Care Med 2019;20(4):332–339. DOI: 10.1097/PCC.0000000000001866.
  5. Devarajan P. The current state of the art in acute kidney injury. Front Pediatr 2020;8:70. DOI: 10.3389/fped.2020.00070.
  6. Basu RK, Chawla LS, Wheeler DS, Goldstein SL. Renal angina: An emerging paradigm to identify children at risk for acute kidney injury. Pediatr Nephrol 2012;27(7):1067–1078. DOI: 10.1007/s00467-011- 2024-5.
  7. Bihorac A, Chawla S, Shaw D, Al-Khafaji A, Davison L, Demuth E, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit. Care Med 2014;189(8):932–939. DOI: 10.1164/rccm.201401-0077OC.
  8. Yang QH, Liu DW, Long Y, Liu HZ, Chai WZ, Wang XT. Acute renal failure during sepsis: Potential role of cell cycle regulation. J Infect 2009;58(6):459–464. DOI: 10.1016/j.jinf.2009.04.003.
  9. Westhoff JH, Schildhorn C, Jacobi C, Hömme M, Hartner A, Braun H, et al. Telomere shortening reduces regenerative capacity after acute kidney injury. J Am Soc Nephrol 2010;21(2):327–236. DOI: 10.1681/ASN.2009010072.
  10. Vijayan A, Faubel S, Askenazi J, Cerda J, Fissell H, Heung M, et al. Clinical use of the urine biomarker [TIMP- 2] × [IGFBP7] for acute kidney injury risk assessment. Am J Kidney Dis 2016;68:19–28. DOI: 10.1053/j.ajkd.2015.12.033.
  11. Westhoff JH, Tönshoff B, Waldherr S, Pöschl J, Teufel U, Westhoff TH, et al. Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) • insulin-like growth factor-binding protein 7 (IGFBP7) predicts adverse outcome in pediatric acute kidney injury. PLoS One 2015;10(11):e0143628. DOI: 10.1371/journal.pone.0143628.
  12. Rizvi MS, Kashani KB. Biomarkers for early detection of acute kidney injury. J Appl Lab Med 2017;2(3):386–399. DOI: 10.1373/jalm.2017.023325.
  13. Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a pediatric sequential organ failure assessment score and evaluation of the sepsis-3 definitions in critically ill children. JAMA Pediatr 2017;171(10):e172352. DOI: 10.1001/jamapediatrics.2017.2352.
  14. El-Mashad GM, El-Mekkawy MS, Zayan MH. A new mortality prediction score in the paediatric intensive care unit. An Pediatr (Engl Ed) 2020;92(5):277–285. DOI: 10.1016/j.anpedi.2019.05.018.
  15. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009;20(3):629–637. DOI: 10.1681/ASN.2008030287.
  16. Zappitelli M. Epidemiology and diagnosis of acute kidney injury. Semin Nephrol 2008;28(5):436–446. DOI: 10.1016/j.semnephrol.2008. 05.003.
  17. Chen J, Sun Y, Wang S, Dai X, Huang H, Bai Z, et al. The effectiveness of urinary TIMP-2 and IGFBP-7 in predicting acute kidney injury in critically ill neonates. Pediatr Res 2020; 87(6):1052–1059. DOI: 10.1038/s41390-019-0698-8.
  18. Tenny S, Varacallo M. Evidence Based Medicine. In: Stat Pearls [Internet]. Treasure Island (FL). StatPearls Publishing 2020;22:234–237. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470182/.
  19. Shimelis D, Abebe B, Deyessa N. Incidence of acute kidney injury and determinant factors in children admitted to a tertiary hospital. IOSR J Dent Med Sci 2018;17(3):48–53. DOI: 10.9790/0853-1703094853.
  20. Peerapornratana S, Manrique-Caballero CL, Gómez H, Kellum JA. Acute kidney injury from sepsis: Current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int 2019;96(5):1083–1099. DOI: 10.1016/j.kint.2019.05.026.
  21. Suarez J, Busse LW. New strategies to optimize renal haemodynamics. Curr Opin Crit Care 2020;26(6):536–542. DOI: 10.1097/MCC.0000000000000774.
  22. Olowu WA, Niang A, Osafo C, Ashuntantang G, Arogundade FA, Porter J, et al. Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: A systematic review. Lancet Glob Health 2016;4(4):e242–e250. DOI: 10.1016/S2214-109X(15)00322-8.
  23. Halle MP, Ashuntantang G, Kaze FF, Takongue C, Kengne AP. Fatal outcomes among patients on maintenance haemodialysis in sub-Saharan Africa: A 10-year audit from the Douala General Hospital in Cameroon. BMC Nephrol 2016;17(1):165. DOI: 10.1186/s12882-016-0377-5.
  24. Sutherland SM, Byrnes JJ, Kothari M, Longhurst CA, Dutta S, Garcia P, et al. AKI in hospitalized children: Comparing the pRIFLE, AKIN, and KDIGO definitions. Clin J Am Soc Nephrol 2015;10(4):554–561. DOI: 10.2215/CJN.01900214.
  25. Sethi SK, Bunchman T, Chakraborty R, Raina R. Pediatric acute kidney injury: New advances in the last decade. Kidney Res Clin Pract 2021;40(1):40–51. DOI: 10.23876/j.krcp.20.074.
  26. Raina R, Chakraborty R, Tibrewal A, Sethi SK, Bunchman T. Advances in pediatric acute kidney injury. Pediatr Res 2022;91(1):44–55. DOI: 10.1038/s41390-021-01452-3.
  27. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012;120(4):c179–c184. DOI: 10.1159/000339789.
  28. Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta 2015;438:350–357. DOI: 10.1016/j.cca.2014.08.039.
  29. Goldstein SL. Urine output assessment in acute kidney injury. The cheapest and most impactful biomarker. Front Pediatr 2020;7:565. DOI: 10.3389/fped.2019.00565.
  30. Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, Thakar CV, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis 2013;61(5):649–672. DOI: 10.1053/j.ajkd.2013.02.349.
  31. Ronco C. Acute kidney injury: From clinical to molecular diagnosis. Crit Care 2016;20(1):201. DOI: 10.1186/s13054-016-1373-7.
  32. Koyner JL, Shaw AD, Chawla LS, Hoste EA, Bihorac A, Kashani K, et al. Tissue inhibitor metalloproteinase-2 (TIMP-2). IGF-binding protein-7 (IGFBP7) levels are associated with adverse long-term outcomes in patients with AKI. J Am Soc Nephrol 2015;26(7):1747–1754. DOI: 10.1681/ASN.2014060556.
  33. Honore PM, Nguyen HB, Gong M, Chawla LS, Bagshaw SM, Artigas A, et al. Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 for risk stratification of acute kidney injury in patients with sepsis. Crit Care Med 2016;44(10):1851–1860. DOI: 10.1097/CCM.0000000000001827.
  34. Wetz AJ, Richardt EM, Wand S, Kunze N, Schotola H, Quintel M, et al. Quantification of urinary TIMP-2 and IGFBP-7: An adequate diagnostic test to predict acute kidney injury after cardiac surgery? Crit Care 2015;19(1):3. DOI: 10.1186/s13054-014-0717-4.
  35. Hoste EA, McCullough PA, Kashani K, Chawla LS, Joannidis M, Shaw AD, et al. Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers. Nephrol Dial Transplant 2014;29(11):2054–2061. DOI: 10.1093/ndt/gfu292.
  36. Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 2013;17(1):R25–R28. DOI: 10.1186/cc12503.
  37. Zhang D, Yuan Y, Guo L, Wang Q. Comparison of urinary TIMP-2 and IGFBP7 cut-offs to predict acute kidney injury in critically ill patients: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore) 2019;98(26):e16232. DOI: 10.1097/MD.00000000000 16232.
  38. Adler C, Heller T, Schregel F, Hagmann H, Hellmich M, Adler J, et al. TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors. Crit Care 2018;22(1):126. DOI: 10.1186/s13054-018-2042-9.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.