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Serum cystatin C for acute kidney injury evaluation in children treated with aminoglycosides

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Abstract

Background

Serum cystatin C (CysC) is a more accurate glomerular filtration rate marker than serum creatinine (SCr) and may rise more quickly with acute kidney injury (AKI).

Methods

We performed a prospective cohort study of 81 non-critically ill children during 110 aminoglycoside (AG) treatments. We calculated area under the curve (AUC) for CysC to diagnose SCr-defined AKI and predict persistent AKI. SCr-AKI definition was based on the Kidney Disease: Improving Global Outcomes (≥stage 1: ≥50 % or 26.5 μmol/l SCr rise from baseline; stage 2: SCr doubling); CysC-AKI was based on a modified version using CysC rise.

Results

SCr-AKI and CysC-AKI developed in 45 and 48 % treatments, respectively. CysC rise predicted stage 1 (AUC = 0.75, 95 % CI 0.60–0.90) and 2 (AUC = 0.85, 95 % CI 0.75–0.95) SCr-AKI 2 days before SCr-AKI attainment. The best combined sensitivity/specificity for percent CysC rise to predict stage 1 SCr-AKI was with a 44 % CysC rise (sensitivity = 65 %, specificity = 83 %). CysC rise on day of SCr-AKI development was associated with SCr-AKI ≥48 h (AUC = 0.73, 95 % CI 0.56–0.90) and ≥50 % persistent SCr rise at treatment end (AUC = 0.76, 95 % CI 0.61–0.90).

Conclusions

CysC is as an early AKI biomarker and predictive of persistent AKI on aminoglycoside treatment.

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References

  1. Alkandari O, Eddington KA, Hyder A, Gauvin F, Ducruet T, Gottesman R, Phan V, Zappitelli M (2011) Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study. Crit Care 15:R146

    Article  PubMed  PubMed Central  Google Scholar 

  2. Arora P, Kher V, Rai PK, Singhal MK, Gulati S, Gupta A (1997) Prognosis of acute renal failure in children: a multivariate analysis. Pediatr Nephrol 11:153–155

    Article  CAS  PubMed  Google Scholar 

  3. Baskin E, Saygili A, Harmanci K, Agras PI, Ozdemir FN, Mercan S, Tokel K, Saatci U (2005) Acute renal failure and mortality after open-heart surgery in infants. Ren Fail 27:557–560

    Article  PubMed  Google Scholar 

  4. Blinder JJ, Goldstein SL, Lee VV, Baycroft A, Fraser CD, Nelson D, Jefferies JL (2012) Congenital heart surgery in infants: effects of acute kidney injury on outcomes. J Thorac Cardiovasc Surg 143:368–374

    Article  PubMed  Google Scholar 

  5. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW (2005) Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16:3365–3370

    Article  PubMed  Google Scholar 

  6. Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, Kellum JA (2006) RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 10:R73

    Article  PubMed  PubMed Central  Google Scholar 

  7. Prodhan P, McCage LS, Stroud MH, Gossett J, Garcia X, Bhutta AT, Schexnayder S, Maxson RT, Blaszak RT (2012) Acute kidney injury is associated with increased in-hospital mortality in mechanically ventilated children with trauma. J Trauma Acute Care Surg 73:832–837

    Article  PubMed  Google Scholar 

  8. Li S, Krawczeski CD, Zappitelli M, Devarajan P, Thiessen-Philbrook H, Coca SG, Kim RW, Parikh CR, Consortium T-A (2011) Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: a prospective multicenter study. Crit Care Med 39:1493–1499

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hui-Stickle S, Brewer ED, Goldstein SL (2005) Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001. Am J Kidney Dis 45:96–101

    Article  PubMed  Google Scholar 

  10. Misurac JM, Knoderer CA, Leiser JD, Nailescu C, Wilson AC, Andreoli SP (2013) Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children. J Pediatr 162:1153–9, 9.e1

  11. Moffett BS, Goldstein SL (2011) Acute kidney injury and increasing nephrotoxic-medication exposure in noncritically-ill children. Clin J Am Soc Neprol 6:856–863

    Article  Google Scholar 

  12. Zappitelli M, Moffett BS, Hyder A, Goldstein SL (2011) Acute kidney injury in non-critically ill children treated with aminoglycoside antibiotics in a tertiary healthcare centre: a retrospective cohort study. Nephrol Dial Transplant 26:144–150

    Article  PubMed  Google Scholar 

  13. Al-Aloul M, Miller H, Alapati S, Stockton PA, Ledson MJ, Walshaw MJ (2005) Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use. Pediatr Pulmonol 39:15–20

    Article  CAS  PubMed  Google Scholar 

  14. Frisk P, Bratteby LE, Carlson K, Lönnerholm G (2002) Renal function after autologous bone marrow transplantation in children: a long-term prospective study. Bone Marrow Transplant 29:129–136

    Article  CAS  PubMed  Google Scholar 

  15. Glass S, Plant ND, Spencer DA (2005) The effects of intravenous tobramycin on renal tubular function in children with cystic fibrosis. J Cyst Fibros 4:221–225

    Article  CAS  PubMed  Google Scholar 

  16. Pannu N, Nadim MK (2008) An overview of drug-induced acute kidney injury. Crit Care Med 36:S216–S223

    Article  CAS  PubMed  Google Scholar 

  17. Smyth A, Lewis S, Bertenshaw C, Choonara I, McGaw J, Watson A (2008) Case–control study of acute renal failure in patients with cystic fibrosis in the UK. Thorax 63:532–535

    Article  CAS  PubMed  Google Scholar 

  18. Menon S, Kirkendall ES, Nguyen H, Goldstein SL (2014) Acute kidney injury associated with high nephrotoxic medication exposure leads to chronic kidney disease after 6 months. J Pediatr 165:522–527.e2

  19. Coca SG, Yalavarthy R, Concato J, Parikh CR (2008) Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review. Kidney Int 73:1008–1016

    Article  CAS  PubMed  Google Scholar 

  20. Waikar SS, Bonventre JV (2007) Biomarkers for the diagnosis of acute kidney injury. Curr Opin Nephrol Hypertens 16:557–564

    Article  PubMed  Google Scholar 

  21. Du Y, Zappitelli M, Mian A, Bennett M, Ma Q, Devarajan P, Mehta R, Goldstein SL (2011) Urinary biomarkers to detect acute kidney injury in the pediatric emergency center. Pediatr Nephrol 26:267–274

    Article  PubMed  Google Scholar 

  22. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238

    Article  CAS  PubMed  Google Scholar 

  23. Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, Kim RW, Koyner JL, Coca SG, Edelstein CL, Shlipak MG, Garg AX, Krawczeski CD, Consortium T-A (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL (2007) Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 11:R84

    Article  PubMed  PubMed Central  Google Scholar 

  25. Grubb A, Nyman U, Björk J, Lindström V, Rippe B, Sterner G, Christensson A (2005) Simple cystatin c–based prediction equations for glomerular filtration rate compared with the modification of diet in renal disease prediction equation for adults and the Schwartz and the Counahan–Barratt prediction equations for children. Clin Chem 51:1420–1431

    Article  CAS  PubMed  Google Scholar 

  26. Laterza OF, Price CP, Scott MG (2002) Cystatin C: an improved estimator of glomerular filtration rate? Clin Chem 48:699–707

    CAS  PubMed  Google Scholar 

  27. Filler G, Lepage N (2003) Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol 18:981–985

    Article  PubMed  Google Scholar 

  28. Zappitelli M, Parvex P, Joseph L, Paradis G, Grey V, Lau S, Bell L (2006) Derivation and validation of cystatin C–based prediction equations for GFR in children. Am J Kidney Dis 48:221–230

    Article  CAS  PubMed  Google Scholar 

  29. Briguori C, Visconti G, Rivera NV, Focaccio A, Golia B, Giannone R, Castaldo D, De Micco F, Ricciardelli B, Colombo A (2010) Cystatin C and contrast-induced acute kidney injury. Circulation 121:2117–2122

    Article  CAS  PubMed  Google Scholar 

  30. Quintavalle C, Fiore D, De Micco F, Visconti G, Focaccio A, Golia B, Ricciardelli B, Donnarumma E, Bianco A, Zabatta MA, Troncone G, Colombo A, Briguori C, Condorelli G (2012) Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury. Circulation 126:3008–3016

    Article  CAS  PubMed  Google Scholar 

  31. Ricci Z, Luciano R, Favia I, Garisto C, Muraca M, Morelli S, Di Chiara L, Cogo P, Picardo S (2011) High-dose fenoldopam reduces postoperative neutrophil gelatinase-associated lipocaline and cystatin C levels in pediatric cardiac surgery. Crit Care 15:R160

    Article  PubMed  PubMed Central  Google Scholar 

  32. Zhang Z, Lu B, Sheng X, Jin N (2011) Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis. Am J Kidney Dis 58:356–365

    Article  CAS  PubMed  Google Scholar 

  33. Krawczeski CD, Woo JG, Wang Y, Bennett MR, Ma Q, Devarajan P (2011) Neutrophil gelatinase-associated lipocalin concentrations predict development of acute kidney injury in neonates and children after cardiopulmonary bypass. J Pediatr 158:1009–1015. e1

  34. Kidney Disease: Improving Global Outcomes Acute Kidney Injury Work Group (2012) KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int 2:1–138

    Article  Google Scholar 

  35. Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kellum JA, Lameire N (2013) Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 17:204

    Article  PubMed  PubMed Central  Google Scholar 

  37. Zappitelli M, Parikh CR, Akcan-Arikan A, Washburn KK, Moffett BS, Goldstein SL (2008) Ascertainment and epidemiology of acute kidney injury varies with definition interpretation. Clin J Am Soc Nephrol 3:948–954

    Article  PubMed  PubMed Central  Google Scholar 

  38. Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, Bennett M, Devarajan P (2011) Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol 58:2301–2309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zappitelli M, Krawczeski CD, Devarajan P, Wang Z, Sint K, Thiessen-Philbrook H, Li S, Bennett MR, Ma Q, Shlipak MG (2011) Early postoperative serum cystatin C predicts severe acute kidney injury following pediatric cardiac surgery. Kidney Int 80:655–662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Herget-Rosenthal S, Marggraf G, Hüsing J, Göring F, Pietruck F, Janssen O, Philipp T, Kribben A (2004) Early detection of acute renal failure by serum cystatin C. Kidney Int 66:1115–1122

    Article  CAS  PubMed  Google Scholar 

  41. Soto K, Coelho S, Rodrigues B, Martins H, Frade F, Lopes S, Cunha L, Papoila AL, Devarajan P (2010) Cystatin C as a marker of acute kidney injury in the emergency department. Cliin J Am Soc Nephrol 5:1745–1754

    Article  CAS  Google Scholar 

  42. Wald R, Liangos O, Perianayagam MC, Kolyada A, Herget-Rosenthal S, Mazer CD, Jaber BL (2010) Plasma cystatin C and acute kidney injury after cardiopulmonary bypass. Clin J Am Soc Nephrol 5:1373–1379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Dr. Zappitelli received institutional funding from the McGill University Health Centre Research Institute, the Kidney Research Scientist Core Education and National Training Program and the Fonds de Recherches en Santé du Québec to support this work. PD is supported by NIH grant P50 DK096418.

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Correspondence to Michael Zappitelli.

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Institutional ethics boards approved the study before initiation. All procedures performed in the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent/assent was obtained before participation.

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The authors declare that they have no conflict of interest.

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Lau, L., Al-Ismaili, Z., Harel-Sterling, M. et al. Serum cystatin C for acute kidney injury evaluation in children treated with aminoglycosides. Pediatr Nephrol 32, 163–171 (2017). https://doi.org/10.1007/s00467-016-3450-1

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  • DOI: https://doi.org/10.1007/s00467-016-3450-1

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