Skip to main content

Advertisement

SpringerLink
Log in

Cystatin C: best biomarker for acute kidney injury and estimation of glomerular filtration rate in childhood cirrhosis

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The objective of the study was to evaluate the diagnostic and prognostic role of serum cystatin C, urinary neutrophil gelatinase–associated lipocalin (NGAL), and renal resistive index (RRI) in AKI among pediatric cirrhotics. The study included cirrhotic children under 18 years of age. AKI was diagnosed as per Kidney Diseases–Improving Global Outcomes (KDIGO) guidelines. All patients underwent measurement of serum cystatin C, urinary NGAL, and RRI at baseline, 3 months, and 6 months. eGFR was calculated using both creatinine- and cystatin-based equations. Of the 247 cirrhotics admitted during the study, 100 gave consent and were included. Forty-one fulfilled the KDIGO definition of AKI of whom 22 showed resolution. Two of these children had a repeat AKI at 2 and 4 months after initial AKI; both resolved with medical management. On logistic regression analysis, serum cystatin C (OR: 544.8, 95% CI: 24.4–12170, p < 0.0005) and urinary NGAL (OR: 1.006, 95% CI: 1001–1.012, p = 0.019) were found to be significantly associated with AKI. Cystatin C alone was the best biomarker for diagnosing AKI in children with decompensation (OR: 486.7, p < 0.0005) or spontaneous bacterial peritonitis (p = 0.02). eGFR calculated by serum cystatin C–based formulas was more reliable than that calculated by creatinine-based equations.

Conclusion: Serum cystatin C is the best biomarker for diagnosis of AKI in pediatric cirrhotics, especially with decompensation and SBP. eGFR calculated on serum cystatin C–based equations is more reliable than creatinine-based ones.

What is Known:

• Acute kidney injury (AKI) is a common complication in cirrhotic adults.

• Newer biomarkers have diagnostic and prognostic role in adult cirrhotics.

What is New:

• Serum cystatin C is a useful biomarker to identify acute kidney injury in cirrhotic children with decompensation.

• Glomerular filtration rate calculation is more accurate by cystatin-based equations than creatinine-based equations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data and material

Yes, with first author.

Code availability

Not applicable.

Abbreviations

ACLF:

Acute-on-chronic liver failure

AKI:

Acute kidney injury

AUROC:

Area under the receiver operating characteristic curve

CI:

Confidence interval

CLD:

Chronic liver disease

eGFR:

Estimated glomerular filtration rate

GFR:

Glomerular filtration rate

HRS:

Hepatorenal syndrome

IAC:

International Ascites Club

KDIGO:

Kidney Diseases–Improving Global Outcomes

MELD:

Model for end-stage liver disease

NGAL:

Neutrophil gelatinase–associated lipocalin

PELD:

Pediatric end-stage liver disease

RRI:

Renal resistive index

SD:

Standard deviation

References

  1. Piano S, Rosi S, Maresio G et al (2013) Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites. J Hepatol 59(3):482–489

    Article  Google Scholar 

  2. Garcia-Tsao G, Parikh CR, Viola A (2008) Acute kidney injury in cirrhosis. Hepatology. 48(6):2064–2077

    Article  CAS  Google Scholar 

  3. Tariq R, Hadi Y, Chahal K, Reddy S, Salameh H, Singal AK (2020) Incidence, mortality and predictors of acute kidney injury in patients with cirrhosis: A systematic review and meta-analysis. J Clin Transl Hepatol 8(2):135–142

    Article  Google Scholar 

  4. Chung MY, Jun DW, Sung SA (2010) Diagnostic value of cystatin C for predicting acute kidney injury in patients with liver cirrhosis. Korean J Hepatol 16(3):301–307

    Article  Google Scholar 

  5. Kamath BM, Podkameni G, Hutchinson AL et al (2012) Renal anomalies in Alagille syndrome: A disease-defining feature. Am J Med Genet A 158A(1):85–89

    Article  Google Scholar 

  6. Dzieżyc-Jaworska K, Litwin T, Członkowska A (2019) Clinical manifestations of Wilson disease in organs other than the liver and brain. Ann Transl Med 7(Suppl 2):S62

    Article  Google Scholar 

  7. Hansen K, Horslen S (2008) Metabolic liver disease in children. Liver Transpl 14(5):713–733

    Article  Google Scholar 

  8. Lal BB, Alam S, Sood V, Rawat D, Khanna R (2018) Profile, risk factors and outcome of acute kidney injury in paediatric acute-on-chronic liver failure. Liver Int 38(10):1777–1784

    Article  CAS  Google Scholar 

  9. Cholongitas E, Senzolo M, Patch D, Shaw S, O’Beirne J, Burroughs AK (2009) Cirrhotics admitted to intensive care unit: The impact of acute renal failure on mortality. Eur J Gastroenterol Hepatol 21(7):744–750

    Article  Google Scholar 

  10. Belcher JM, Parikh CR, Garcia-Tsao G (2013) Acute kidney injury in patients with cirrhosis: Perils and promise. Clin Gastroenterol Hepatol 11(12):1550–1558

    Article  CAS  Google Scholar 

  11. Woitas RP, Stoffel-Wagner B, Flommersfeld S et al (2000) Correlation of serum concentrations of cystatin C and creatinine to inulin clearance in liver cirrhosis. Clin Chem 46(5):712–715

    Article  CAS  Google Scholar 

  12. Barreto R, Elia C, Solà E et al (2014) Urinary neutrophil gelatinase-associated lipocalin predicts kidney outcome and death in patients with cirrhosis and bacterial infections. J Hepatol 61(1):35–42

    Article  CAS  Google Scholar 

  13. Goyal S, Dixit VK, Jain AK, Shukla RC, Ghosh J, Kumar V (2013) Intrarenal resistance index (RI) as a predictor of early renal impairment in patients with liver cirrhosis. Trop Gastroenterol 34(4):235–239

    Article  Google Scholar 

  14. Aydogdu S, Akil I, Akil T et al (2004) Renal resistive indexes and some renal functions in liver cirrhotic children. Pediatr Int 46(1):67–71. https://doi.org/10.1111/j.1442-200X.2004.01826.x

    Article  PubMed  Google Scholar 

  15. Mowat C, Stanley AJ (2001) Review article: Spontaneous bacterial peritonitis--Diagnosis, treatment and prevention. Aliment Pharmacol Ther 15(12):1851–1859. https://doi.org/10.1046/j.1365-2036.2001.01116.x

    Article  CAS  PubMed  Google Scholar 

  16. Kellum JA, Lameire N, KDIGO AKI Guideline Work Group (2013) Diagnosis, evaluation, and management of acute kidney injury: A KDIGO summary (Part 1). Crit Care 17(1):204

    Article  Google Scholar 

  17. Arroyo V, Ginès P, Gerbes AL et al (1996) Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 23(1):164–176

    Article  CAS  Google Scholar 

  18. Jindal A, Bhadoria AS, Maiwall R, Sarin SK (2016) Evaluation of acute kidney injury and its response to terlipressin in patients with acute-on-chronic liver failure. Liver Int 36(1):59–67

    Article  CAS  Google Scholar 

  19. Boddi M, Bonizzoli M, Chiostri M et al (2016) Renal resistive index and mortality in critical patients with acute kidney injury. Eur J Clin Investig 46(3):242–251

    Article  Google Scholar 

  20. Muhari-Stark E, Burckart GJ (2018) Glomerular filtration rate estimation formulas for pediatric and neonatal use. J Pediatr Pharmacol Ther 23(6):424–431

    PubMed  PubMed Central  Google Scholar 

  21. Berg UB, Nemeth A (2018) Well preserved renal function in children with untreated chronic liver disease. J Pediatr Gastroenterol Nutr 66(4):575–580

    Article  Google Scholar 

  22. D’Amico G, Garcia-Tsao G, Pagliaro L (2006) Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. J Hepatol 44(1):217–231

    Article  Google Scholar 

  23. Randers E, Krue S, Erlandsen EJ, Danielsen H, Hansen LG (1999) Reference interval for serum cystatin C in children. Clin Chem 45(10):1856–1858

    Article  CAS  Google Scholar 

  24. Ziegelasch N, Vogel M, Müller E et al (2019) Cystatin C serum levels in healthy children are related to age, gender, and pubertal stage. Pediatr Nephrol 34(3):449–457

    Article  Google Scholar 

  25. Samyn M, Cheeseman P, Bevis L et al (2005) Cystatin C, an easy and reliable marker for assessment of renal dysfunction in children with liver disease and after liver transplantation. Liver Transpl 11(3):344–349

    Article  Google Scholar 

  26. Maiwall R, Kumar A, Bhardwaj A, Kumar G, Bhadoria AS, Sarin SK (2018) Cystatin C predicts acute kidney injury and mortality in cirrhotics: A prospective cohort study. Liver Int 38(4):654–664

    Article  CAS  Google Scholar 

  27. Maiwall R, Pasupuleti SSR, Bihari C et al (2020) Incidence, Risk Factors, and Outcomes of transition of acute kidney injury to chronic kidney disease in cirrhosis: A prospective cohort study. Hepatology. 71(3):1009–1022

    Article  CAS  Google Scholar 

  28. Singer E, Elger A, Elitok S et al (2011) Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes. Kidney Int 80(4):405–414. https://doi.org/10.1038/ki.2011.41

    Article  CAS  PubMed  Google Scholar 

  29. Jo SK, Yang J, Hwang SM, Lee MS, Park SH (2019) Role of biomarkers as predictors of acute kidney injury and mortality in decompensated cirrhosis. Sci Rep 9(1):14508

    Article  Google Scholar 

  30. Mindikoglu AL, Dowling TC, Wong-You-Cheong JJ et al (2014) A pilot study to evaluate renal hemodynamics in cirrhosis by simultaneous glomerular filtration rate, renal plasma flow, renal resistive indices and biomarkers measurements. Am J Nephrol 39(6):543–552

    Article  CAS  Google Scholar 

  31. Deng F, Finer G, Haymond S, Brooks E, Langman CB (2015) Applicability of estimating glomerular filtration rate equations in pediatric patients: comparison with a measured glomerular filtration rate by iohexol clearance. Transl Res 165(3):437–445

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India

    Priti Vijay MD, Bikrant Bihari Lal MD, DM, Vikrant Sood MD, DM, Rajeev Khanna MD & Seema Alam MD

Authors
  1. Priti Vijay MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bikrant Bihari Lal MD, DM
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vikrant Sood MD, DM
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rajeev Khanna MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seema Alam MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PV, BBL, VS, and SA conceptualized and designed the work. PV acquired the data; PV, BBL, and SA analyzed and reviewed the data, and prepared the first draft. VS, RK, and SA critically reviewed, revised, and approved the final version.

Corresponding author

Correspondence to Seema Alam MD.

Ethics declarations

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Ethics Committee of Institute of Liver and Biliary Sciences, New Delhi, India (IEC/2019/66/NA03).

Consent to participate

Informed, written consent was obtained from parents of all individual participants included in the study.

Consent for publication

Obtained.

Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Peter de Winter

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 11 kb)

ESM 2

(DOCX 30 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vijay, P., Lal, B.B., Sood, V. et al. Cystatin C: best biomarker for acute kidney injury and estimation of glomerular filtration rate in childhood cirrhosis. Eur J Pediatr 180, 3287–3295 (2021). https://doi.org/10.1007/s00431-021-04076-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-021-04076-1

Keywords

Search

Navigation