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

Springer Science and Business Media LLC - Tập 30 - Trang 665-676 - 2014
Paola Lagos-Arevalo1, Ana Palijan1, Laura Vertullo1, Prasad Devarajan2, Michael R. Bennett2, Venkata Sabbisetti3, Joseph V. Bonventre3, Qing Ma2, Ronald D. Gottesman1, Michael Zappitelli1,4
1Department of Pediatrics, McGill University Health Centre, Montreal, Canada
2Nephrology & Hypertension, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA
3Renal Division, Brigham’s and Women’s Hospital, Harvard Medical School, Boston, USA
4Montreal Children's Hospital, Montreal, Canada

Tóm tắt

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. 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. 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). 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.

Tài liệu tham khảo

American Society of Nephrology (2005) American Society of Nephrology renal research report. J Am Soc Nephrol 16:1886–1903 Al-Ismaili Z, Palijan A, Zappitelli M (2011) Biomarkers of acute kidney injury in children: discovery, evaluation, and clinical application. Pediatr Nephrol 26:29–40 Devarajan P (2005) Cellular and molecular derangements in acute tubular necrosis. Curr Opin Pediatr 17:193–199 Devarajan P (2010) Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark Med 4:265–280 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 77:708–714 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 73:863–869 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 22:1737–1747 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 4:237–246 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 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 57:1752–1761 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 Bellomo R (2005) Defining, quantifying, and classifying acute renal failure. Crit Care Clin 21:223–237 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:R31 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 17:204 Atiyeh BA, Dabbagh SS, Gruskin AB (1996) Evaluation of renal function during childhood. Pediatr Rev 17:175–180 Laterza OF, Price CP, Scott MG (2002) Cystatin C: an improved estimator of glomerular filtration rate? Clin Chem 48:699–707 Filler G, Lepage N (2003) Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr Nephrol 18:981–985 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 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 Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C (2003) Impact of thyroid dysfunction on serum cystatin C. Kidney Int 63:1944–1947 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 44:2556–2557 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 356:227–228 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 28:346–349 Pollack MM, Ruttimann UE, Getson PR (1988) Pediatric risk of mortality (PRISM) score. Crit Care Med 16:1110–1116 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 362:192–197 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 20:629–637 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 6:1427–1435 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 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 1:200–208 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 207-112 Pencina MJ, D’Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30:11–21 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 51:1420–1431 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 26:566–571 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 31:2791–2798 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 25:3283–3289 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 80:655–662 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 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 142:148–154 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 27:261–267 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 88:124–130 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 5:1745–1754 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 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 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 29:133–138 Pickering JW, Endre ZH (2013) Linking injury to outcome in acute kidney injury: a matter of sensitivity. PLoS ONE 8:e62691