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01.04.2015 | Original Article

Cystatin C in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine?

verfasst von: Paola Lagos-Arevalo, Ana Palijan, Laura Vertullo, Prasad Devarajan, Michael R. Bennett, Venkata Sabbisetti, Joseph V. Bonventre, Qing Ma, Ronald D. Gottesman, Michael Zappitelli

Erschienen in: Pediatric Nephrology | Ausgabe 4/2015

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Abstract

Background

Early acute kidney injury (AKI) diagnosis is needed to pursue treatment trials. We evaluated cystatin C (CysC) as an early biomarker of serum creatinine (SCr)-AKI and an alternative to define AKI.

Methods

We studied 160 non-cardiac children in the intensive care unit (ICU). We measured daily CysC and SCr. AKI was staged by KDIGO (Kidney Disease: Improving Global Outcomes) guidelines using SCr and CysC (CysC-AKI). We calculated area under the curve (AUC) for (1) neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and urine CysC to diagnose SCr- and CysC-AKI; and (2) for CysC to diagnose SCr-AKI. We evaluated AKI associations with length of stay and ventilation duration.

Results

We found that 44 % of patients developed SCr-AKI; 32 % developed CysC-AKI. Early ICU NGAL was most diagnostic of CysC-AKI (AUC 0.69, 95% CI 0.54–0.84); IL-18 was most diagnostic for SCr-AKI (AUC 0.69 95% CI 0.55–0.82). Combining SCr and CysC-AKI definition led to higher biomarker diagnostic AUC’s. CysC-AKI was not more strongly associated with clinical outcomes. Early ICU CysC predicted SCr-AKI development (AUC 0.70, 95 % CI 0.53–0.89).

Conclusions

Our findings do not support replacing SCr by CysC to define AKI. Early ICU CysC predicts SCr-AKI development and combined SCr-CysC-AKI definition leads to stronger AKI biomarker associations.

American Society of Nephrology (2005) American Society of Nephrology renal research report. J Am Soc Nephrol 16:1886–1903CrossRef

Al-Ismaili Z, Palijan A, Zappitelli M (2011) Biomarkers of acute kidney injury in children: discovery, evaluation, and clinical application. Pediatr Nephrol 26:29–40CrossRefPubMed

Devarajan P (2005) Cellular and molecular derangements in acute tubular necrosis. Curr Opin Pediatr 17:193–199CrossRefPubMed

Devarajan P (2010) Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark Med 4:265–280CrossRefPubMedCentralPubMed

Ferguson MA, Vaidya VS, Waikar SS, Collings FB, Sunderland KE, Gioules CJ, Bonventre JV (2010) Urinary liver-type fatty acid-binding protein predicts adverse outcomes in acute kidney injury. Kidney Int 77:708–714CrossRefPubMedCentralPubMed

Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV (2008) Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 73:863–869CrossRefPubMedCentralPubMed

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, TRIBE-AKI Consortium (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1747CrossRefPubMedCentralPubMed

Aydoğdu M, Gürsel G, Sancak B, Yeni S, Sarı G, Taşyürek S, Türk M, Yüksel S, Senez M, Ozis TN (2013) The use of plasma and urine neutrophil gelatinase associated lipocalin (NGAL) and cystatin-C in early diagnosis of septic acute kidney injury in critically ill patients. Dis Markers 4:237–246CrossRef

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 26:267–274CrossRefPubMed

10.

Haase M, Devarajan P, Haase-Fielitz A, Bellomo R, Cruz DN, Wagener G, Krawczeski CD, Koyner JL, Murray P, Zappitelli M, Goldstein SL, Makris K, Ronco C, Martensson J, Martling CR, Venge P, Siew E, Ware LB, Ikizler TA, Mertens PR (2011) The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol 57:1752–1761CrossRefPubMed

11.

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:R84CrossRefPubMedCentralPubMed

12.

Bellomo R (2005) Defining, quantifying, and classifying acute renal failure. Crit Care Clin 21:223–237CrossRefPubMed

13.

Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Acute Kidney Injury Network (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31CrossRefPubMedCentralPubMed

14.

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 17:204CrossRefPubMedCentralPubMed

15.

Atiyeh BA, Dabbagh SS, Gruskin AB (1996) Evaluation of renal function during childhood. Pediatr Rev 17:175–180CrossRefPubMed

16.

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

17.

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

18.

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 48:221–230CrossRefPubMed

19.

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 66:1115–1122CrossRefPubMed

20.

Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C (2003) Impact of thyroid dysfunction on serum cystatin C. Kidney Int 63:1944–1947CrossRefPubMed

21.

Kos J, Stabuc B, Cimerman N, Brünner N (1998) Serum cystatin C, a new marker of glomerular filtration rate, is increased during malignant progression. Clin Chem 44:2556–2557PubMed

22.

Manetti L, Genovesi M, Pardini E, Grasso L, Lupi I, Linda Morselli L, Pellegrini G, Martino E (2005) Early effects of methylprednisolone infusion on serum cystatin C in patients with severe Graves’ ophthalmopathy. Clin Chim Acta 356:227–228CrossRefPubMed

23.

Manetti L, Pardini E, Genovesi M, Campomori A, Grasso L, Morselli LL, Lupi I, Pellegrini G, Bartalena L, Bogazzi F, Martino E (2005) Thyroid function differently affects serum cystatin C and creatinine concentrations. J Endocrinol Invest 28:346–349CrossRefPubMed

24.

Pollack MM, Ruttimann UE, Getson PR (1988) Pediatric risk of mortality (PRISM) score. Crit Care Med 16:1110–1116CrossRefPubMed

25.

Leteurtre S, Martinot A, Duhamel A, Proulx F, Grandbastien B, Cotting J, Gottesman R, Joffe A, Pfenninger J, Hubert P, Lacroix J, Leclerc F (2003) Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet 362:192–197CrossRefPubMed

26.

Schwartz GJ, Munoz 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 20:629–637CrossRefPubMedCentralPubMed

27.

Fadrowski JJ, Neu AM, Schwartz GJ, Furth SL (2011) Pediatric GFR estimating equations applied to adolescents in the general population. Clin J Am Soc Nephrol 6:1427–1435CrossRefPubMedCentralPubMed

28.

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, e1CrossRefPubMed

29.

Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, Bradwin G, Matsouaka R, Betensky RA, Curhan GC, Bonventre JV (2008) Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl Sci 1:200–208CrossRefPubMedCentralPubMed

30.

Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172, discussion 207-112CrossRefPubMed

31.

Pencina MJ, D’Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30:11–21CrossRefPubMedCentralPubMed

32.

Grubb A, Nyman U, Bjork J, Lindstrom 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 51:1420–1431CrossRefPubMed

33.

Kwon SH, Hyun J, Jeon JS, Noh H, Han DC (2011) Subtle change of cystatin C, with or without acute kidney injury, associated with increased mortality in the intensive care unit. J Crit Care 26:566–571CrossRefPubMed

34.

Lassus JP, Nieminen MS, Peuhkurinen K, Pulkki K, Siirilä-Waris K, Sund R, Harjola VP, FINN-AKVA study group (2010) Markers of renal function and acute kidney injury in acute heart failure: definitions and impact on outcomes of the cardiorenal syndrome. Eur Heart J 31:2791–2798CrossRefPubMed

35.

Nejat M, Pickering JW, Walker RJ, Endre ZH (2010) Rapid detection of acute kidney injury by plasma cystatin C in the intensive care unit. Nephrol Dial Transplant 25:3283–3289CrossRefPubMed

36.

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

37.

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 121:2117–2122CrossRefPubMed

38.

Choi YS, Shim JK, Kim JC, Kang KS, Seo YH, Ahn KR, Kwak YL (2011) Effect of remote ischemic preconditioning on renal dysfunction after complex valvular heart surgery: a randomized controlled trial. J Thorac Cardiovasc Surg 142:148–154CrossRefPubMed

39.

Cortjens B, Royakkers AA, Determann RM, van Suijlen JD, Kamphuis SS, Foppen J, de Boer A, Wieland CW, Spronk PE, Schultz MJ, Bouman CS (2012) Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation. J Crit Care 27:261–267CrossRefPubMed

40.

Haase M, Bellomo R, Devarajan P, Ma Q, Bennett MR, Möckel M, Matalanis G, Dragun D, Haase-Fielitz A (2009) Novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults. Ann Thorac Surg 88:124–130CrossRefPubMed

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. Clin J Am Soc Nephrol 5:1745–1754CrossRefPubMedCentralPubMed

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 5:1373–1379CrossRefPubMedCentralPubMed

43.

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 58:356–365CrossRefPubMed

44.

Ataei N, Bazargani B, Ameli S, Madani A, Javadilarijani F, Moghtaderi M, Abbasi A, Shams S, Ataei F (2014) Early detection of acute kidney injury by serum cystatin C in critically ill children. Pediatr Nephrol 29:133–138CrossRefPubMed

45.

Pickering JW, Endre ZH (2013) Linking injury to outcome in acute kidney injury: a matter of sensitivity. PLoS ONE 8:e62691CrossRefPubMedCentralPubMed

Titel: Cystatin C in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine?
verfasst von: Paola Lagos-Arevalo
Ana Palijan
Laura Vertullo
Prasad Devarajan
Michael R. Bennett
Venkata Sabbisetti
Joseph V. Bonventre
Qing Ma
Ronald D. Gottesman
Michael Zappitelli
Publikationsdatum: 01.04.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 4/2015
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-014-2987-0

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Cystatin C in acute kidney injury diagnosis: early biomarker or alternative to serum creatinine?