Akute Nierenschädigung - Stellenwert von Biomarkern bei perioperativen und intensivmedizinischen Patienten

Die akute Nierenschädigung beeinträchtigt auch bei scheinbar mildem Verlauf und scheinbar vollständiger Erholung der Nierenfunktion die Kurz- und Langzeitprognose betroffener Patienten, ist aber prinzipiell therapeutisch beeinflussbar. Je größer das Zeitfenster zwischen dem Primärereignis und der Nierenfunktionserholung ist, desto schlechter ist die Prognose. Als wirksame Gegenmaßnahmen werden in Leitlinien die Frühdiagnose und die rasche, multifaktorielle Therapieeinleitung empfohlen, um die auslösenden und unterhaltenden nierenschädlichen Faktoren zu identifizieren und optimale Bedingungen für eine vollständige oder weitgehende Nierenerholung zu schaffen. Verschiedene Maßnahmen sind verfügbar, um eine akute Nierenschädigung bei perioperativen und intensivmedizinischen Patienten frühzeitig zu erkennen und die Behandlung einzuleiten.

Abstract

Acute kidney injury (AKI) impairs short- and long-term prognosis of affected patients even in case of apparantly mild course and ‚full’ recovery as measured by follow-up serum creatinine concentrations. Late or none intervention worsens prognosis. However, there are modifiable factors potentially contributing to preserved long-term renal function. Effective treatment is multifactorial and includes identification and reversal of AKI etiology and generation of a (micro)environment for optimal renal recovery. Available treatment options for AKI in perioperative and critically ill patients will be discussed in the setting of novel kidney biomarkers.

Kernaussagen

• Die akute Nierenschädigung (AKI) ist ein häufiges Krankheitsbild perioperativer und intensivmedizinischer Patienten mit langfristigen renalen und kardiovaskulären Folgeerkrankungen, einer zumindest ebenso schlechten Prognose wie des Myokardinfarkts und hohen Kosten für das Gesundheitssystem.

• Die frühe Diagnosestellung und zeitnahe Versorgung sowie die konsequente Nachsorge dieser Patienten gelten als Voraussetzung für die Primärprävention einer chronischen Niereninsuffizienz.

• Serumkreatininanstieg- bzw. Diureserückgang-basierte Frühwarnsysteme oder neue renale Biomarker können bei der raschen Diagnosestellung hilfreich sein.

• Gängige Behandlungsmaßnahmen können auf der Grundlage klassischer und unter Einbeziehung neuer renaler Biomarker eingeleitet werden.

Schlüsselwörter:

akute Nierenschädigung - Frühwarnsystem - Cystatin C - NGAL - TIMP-2*IGFBP7

Keywords:

acute kidney injury - eAlert - Cystatin C - NGAL - TIMP-2*IGFBP7

• Literatur

• 1 Ishani A, Xue JL, Himmelfarb J, Eggers PW et al. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol 2009; 20: 223-228
• 2 Rimes-Stigare C, Frumento P, Bottai M et al Evolution of chronic renal impairment and long-term mortality after de novo acute kidney injury in the critically ill; a Swedish multi-centre cohort study. Crit Care 2015; 19: 221
• 3 Morgera S, Kraft AK, Siebert G et al Long-term outcomes in acute renal failure patients treated with continuous renal replacement therapies. Am J Kidney Dis 2002; 40: 275-279
• 4 Hoste EA, Clermont G, Kersten A et al RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 2006; 10: R73
• 5 Hoste EA, Bagshaw SM, Bellomo R et al Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 2015; 41: 1411-1423
• 6 Thakar CV, Arrigain S, Worley S et al A clinical score to predict acute renal failure after cardiac surgery. J Am Soc Nephrol 2005; 16: 162-168
• 7 Heise D, Rentsch K, Braeuer A et al Comparison of urinary neutrophil glucosaminidase-associated lipocalin, cystatin C, and α1-microglobulin for early detection of acute renal injury after cardiac surgery. Eur J Cardiothorac Surg 2011; 39: 38-43
• 8 Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012; 2: 1-138
• 9 McCullough PA, Bouchard J, Waikar SS et al Implementation of novel biomarkers in the diagnosis, prognosis, and management of acute kidney injury: executive summary from the tenth consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol 2013; 182: 5-12
• 10 Stewart J et al National Confidential Enquiry into Patient Outcome and Death. Adding insult to injury: a review of the care of patients who died in hospital with a primary diagnosis of acute kidney injury (acute renal failure): a report of the National Confidential Enquiry into Patient Outcome and Death (2009). London: National Confidential Enquiry into Patient Outcome and Death; 2009 im Internet: http://www.ncepod.org.uk/2009report1/Downloads/AKI_report.pdf
• 11 Doi K, Yuen PS, Eisner C et al Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol 2009; 20: 1217-1221
• 12 Lassnigg A, Schmid ER, Hiesmayr M et al Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?. Crit Care Med 2008; 36: 1129-1137
• 13 Kellum JA, Sileanu FE, Murugan R et al Classifying AKI by urine output versus serum creatinine level. J Am Soc Nephrol 2015; 26: 2231-2238
• 14 Uchino S, Kellum JA, Bellomo R et al Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. JAMA 2005; 294: 813-818
• 15 Yang L, Xing G, Wang L et al ISN AKF 0by25 China Consortiums. Acute kidney injury in China: a cross-sectional survey. Lancet 2015; 386: 1465-1471
• 16 Selby NM. Electronic alerts for acute kidney injury. Curr Opin Nephrol Hypertens 2013; 22: 637-642
• 17 Kolhe NV, Staples D, Reilly T et al Impact of compliance with a care bundle on acute kidney injury outcomes: a prospective observational study. PLoS One 2015; 10: e0132279
• 18 Colpaert K, Hoste EA, Steurbaut K et al Impact of real-time electronic alerting of acute kidney injury on therapeutic intervention and progression of RIFLE class. Crit Care Med 2012; 40: 1164-1170
• 19 Rind DM, Safran C, Phillips RS et al Effect of computer-based alerts on the treatment and outcomes of hospitalized patients. Arch Intern Med 1994; 154: 1511-1517
• 20 Prendecki M, Blacker E, Sadeghi-Alavijeh O et al Improving outcomes in patients with Acute Kidney Injury: the impact of hospital based automated AKI alerts. Postgrad Med J 2016; 92: 9-13
• 21 McCoy AB, Waitman LR, Gadd CS et al A computerized provider order entry intervention for medication safety during acute kidney injury: a quality improvement report. Am J Kidney Dis 2010; 56: 832-841
• 22 Kolhe NV, Reilly T, Lung J et al A simple care bundle for use in acute kidney injury: a propensity score matched cohort study. Nephrol Dial Transpl 2016 [Epub ahead of print]
• 23 Selby NM, Crowley L, Fluck RJ et al Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients. Clin J Am Soc Nephrol 2012; 7: 533-540
• 24 Gulliford S, Sloan J. Acute Physicians should take the lead in developing acute kidney injury services in district general hospitals. Acute Medicine 2014; 13: 48-50
• 25 Thomas ME, Sitch A, Baharani J, Dowswell G. Earlier intervention for acute kidney injury: evaluation of an outreach service and a long-term follow-up. Nephrol Dial Transplant 2015; 30: 239-244
• 26 Macedo E, Bouchard J, Soroko SH et al Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients. Crit Care 2010; 14: R82
• 27 Grubb A, Simonsen O, Sturfelt G et al Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate. Acta Med Scand 1985; 218: 499-503
• 28 Grubb A, Horio M, Hansson LO et al Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator. Clin Chem 2014; 60: 974-986
• 29 Zhang Z, Lu B, Sheng X, Jin N. Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis. Am J Kidney Dis 2011; 58: 356-365
• 30 Feng Y, Zhang Y, Li G, Wang L. Relationship of cystatin-C change and the prevalence of death or dialysis need after acute kidney injury: a meta-analysis. Nephrology (Carlton) 2014; 19: 679-684
• 31 Delanaye P, Cavalier E, Morel J et al Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine. BMC Nephrol 2014; 15: 9
• 32 Mishra J, Ma Q, Prada A et al Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003; 14: 2534-2543
• 33 Mori K, Lee HT, Rapoport D et al Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 2005; 115: 610-621
• 34 Mishra J, Mori K, Ma Q et al Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 2004; 15: 3073-3082
• 35 Paragas N, Qiu A, Zhang Q et al The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat Med 2011; 17: 216-222
• 36 Mishra J, Dent C, Tarabishi R et al Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005; 365: 1231-1238
• 37 Haase-Fielitz A, Bellomo R, Devarajan P et al Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery – a prospective cohort study. Crit Care Med 2009; 37: 553-560
• 38 Haase-Fielitz A, Haase M, Devarajan P. Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status. Ann Clin Biochem 2014; 51: 335-351
• 39 Haase M, Bellomo R, Devarajan P et al Novel biomarkers early predict the severity of acute kidney injury after cardiac surgery in adults. Ann Thorac Surg 2009; 88: 124-130
• 40 Haase M, Bellomo R, Devarajan P et al NGAL Meta-analysis Investigator Group. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 2009; 54: 1012-1024
• 41 Zhang A, Cai Y, Wang PF et al Diagnosis and prognosis of neutrophil gelatinase-associated lipocalin for acute kidney injury with sepsis: a systematic review and meta-analysis. Crit Care 2016; 20: 41
• 42 Ho J, Tangri N, Komenda P et al Urinary, plasma, and serum biomarkers‘ utility for predicting acute kidney injury associated with cardiac surgery in adults: a meta-analysis. Am J Kidney Dis 2015; 66: 993-1005
• 43 Wagener G, Gubitosa G, Wang S et al Increased incidence of acute kidney injury with aprotinin use during cardiac surgery detected with urinary NGAL. Am J Nephrol 2008; 28: 576-582
• 44 Haase M, Haase-Fielitz A, Plass M et al Prophylactic perioperative sodium bicarbonate to prevent acute kidney injury following open heart surgery: a multicenter double-blinded randomized controlled trial. PLoS Med 2013; 10: e1001426
• 45 Haase M, Devarajan P, Haase-Fielitz A et al The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol 2011; 57: 1752-1761
• 46 Haase M, Kellum JA, Ronco C. Subclinical AKI – an emerging syndrome with important consequences. Nat Rev Nephrol 2012; 8: 735-739
• 47 Nickolas TL, Schmidt-Ott KM, Canetta P et al Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study. J Am Coll Cardiol 2012; 59: 246-255
• 48 Di Somma S, Magrini L, De Berardinis B et al Additive value of blood neutrophil gelatinase-associated lipocalin to clinical judgement in acute kidney injury diagnosis and mortality prediction in patients hospitalized from the emergency department. Crit Care 2013; 17: R29
• 49 Bellomo R, Ronco C, Kellum JA et al Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8: R204-212
• 50 Mehta RL, Kellum JA, Shah SV et al Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31
• 51 McCullough PA, Shaw AD, Haase M et al Diagnosis of acute kidney injury using functional and injury biomarkers: workgroup statements from the tenth Acute Dialysis Quality Initiative Consensus Conference. Contrib Nephrol 2013; 182: 13-29
• 52 Kashani K, Al-Khafaji A, Ardiles T et al Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 2013; 17: R25
• 53 Hoste EA, McCullough PA, Kashani K et al Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers. Nephrol Dial Transplant 2014; 29: 2054-2061
• 54 Gocze I, Koch M, Renner P et al Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery. PLoS One 2015; 10: e0120863
• 55 Meersch M, Schmidt C, Van Aken H et al Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One 2014; 9: e93460
• 56 Meersch M, Schmidt C, Van Aken H et al Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery. PLoS One 2014; 9: e110865
• 57 Bihorac A, Chawla LS, Shaw AD et al Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med 2014; 189: 932-939
• 58 Cruz DN, Bagshaw SM, Maisel A et al Use of biomarkers to assess prognosis and guide management of patients with acute kidney injury. Contrib Nephrol 2013; 182: 45-64