1 Prof Dr Serhan Tuğlular MÜTF Nefroloji Bilim DalıAKUT BÖBREK HASARI Prof Dr Serhan Tuğlular MÜTF Nefroloji Bilim Dalı

2 Giriş Hastaneye başvuruda 5% YBÜ‘lerinde 30% Yatan Hastaların 2-5%AKI

3 ABY AKI Artan Böbrek Hasarı (Akut Böbrek Hasarı)It now appears that kidney dysfunction is often under-recognized, although its severity is clearly associated with outcome. AKI is now considered the correct nomenclature for the clinical disorder formerly termed ‘acute renal failure’ (ARF). This new taxonomy underscores the fact that AKI exists along a continuum, recognizing that the greater the severity of injury, the more likely it is that the overall outcome will be unfavourable. AKI is not acute tubular necrosis and it is not ARF. Rather, it includes both as well as other, less severe conditions that are not necessarily ‘structural damage’ but also include ‘dysfunction’ (slight, apparently innocuous increases in serum creatinine; decreases in urine output due to volume depletion, generally defining prerenal ARF, with the implied and flawed meaning of a benign and reversible form of renal dysfunction). Instead of focusing exclusively on patients with severe and established renal failure, those who are receiving dialysis and those who have a specific clinical syndrome, the robust association of all AKI classes with hospital mortality behoves us to raise the profile of this disorder as a matter of urgency [2]. 3

4

5 AKI: Tanım Böbrek fonksiyonlarının akut bozulması (48 saat içinde)AKIN redefined AKI as ‘An abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of more than or equal to 0.3 mg/dl, a percentage increase in serum creatinine of more than or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kg per hour for more than six hours).’ Several specifications were provided by the workgroup to this updated definition and were followed by a new staged classification of AKI severity Serum BUN ve Kreatinin  > 0.3mg/dl ve /veya %50 (1.5 x Bazal) İdrar çıkışında azalma <0.5ml/kg/saat > 6 saat 5

6 AKI Klasifikasyonu/Evreleme sistemiSystem Class/Stage Kr Criteria Urine Criteria RIFLE Risk Injury Failure x 1.5 /GFR↓>%25 x 2 / GFR↓>%50 x 3 / GFR↓>%75; Kr>4mg/dl + at least 0.5mg/dl↑ <0.5ml/kg/hr -6 hours <0.5ml/kg/hr-12 hrs Anuria- 12 hrs AKIN Stage 1 Stage 2 Stage 3 >0.3 mg/dl or Basal x 1.5-2 Basal x 2-3 Basal x > 3 or Kr>4mg/dl + at least 0.5mg/dl↑ RRT need <0.5ml/kg/hrs -6 hours <0.5ml/kg/hrs -12 hrs <0.3 ml/kg/hr -24 hrs or anuria-12 hrs 6

7 AKI (+) AKI (-) 45.8 %16.4 Mortalite (%) N=120 AKIN CriteriaKidney Int 2008, 73:- The goal of adopting these sets of explicit diagnostic criteria is to increase clinical awareness and diagnosis of AKI. Both RIFLE and AKIN criteria may cause an increase in false positives, such that some patients regarded as having AKI will not have the condition. Nonetheless, the decision to adopt less inclusive criteria should raise the index of suspicion for AKI, allow its earlier identification during the course of critical illness, and enhance opportunities to prevent or manage kidney damage. Risk for death among patients with AKI. The data were obtained in a recent review of 13 studies that used RIFLE criteria where patient level data on mortality were available for Risk, Injury and Failure patients, as well as those without AKI [3]. The review was conducted to establish a pooled estimate of risk ratio (RR) for mortality for patients of Risk, Injury or Failure classes compared with non-AKI patients. More than 71,000 patients were included in the analysis of published reports. With respect to non-AKI patients, there appeared to be a step-wise increase in RR for death going from Risk class (RR = 2.40) to Injury class (RR = 4.15) and to Failure class (RR = 6.37; P < for all). AKI, acute kidney injury; RIFLE, Risk, Injury, Failure, Loss and Endstage kidney disease. Mortalite (%) AKI (+) AKI (-) 45.8 %16.4 N=120 AKIN Criteria Crit Care Med 2008, 36: 7

8 BELİRTİ VE BULGULAR Bulantı ve kusma Halsizlik İdrar çıkışında azalmaBilinç durumunda değişim/ nöbet Hipervolemi/ hipovolemi Hipertansiyon/ Hipotansiyon Aritmi(Hiperkalemiye ikincil) Nonspesifik karın ağrısı Kanama

9 Laboratory Bulguları BUN ve Kreatinin Hiperkalemi (özellikle oligo-anurik hastada) EKG’de hiperkalemi bulguları Metabolic asidozis Hyperphosfatemia

10 AKI olmaksızın Kr ↑ AKI olmaksızın BUN ↑ Tubuler kreatinin sekresyonunda ↓ Trimethoprim, Cimetidine, Probenecid Yalancı yükselme glukoz, acetoacetate, ascorbic acid, cefoxitin flucytosine Üretiminde artış GI Kanama Katabolik durumlar Corticosteroids Protein yükünde ↑ (TPN-Albumin infusion)

11 AKI Bio-belirteçleri var mı?Sitokinler Platelet aktive edici faktör IL-18 Diğerleri Kidney injury molekül-1 Na/H exchanger isoform-3 Genler Nötrofil gelatinaz associated lipocalin (NGAL) Düşük molekül ağırlıklı proteinler B2-mikroglobulin A1-mikroglobulin Adenozin deaminaz bağlayıcı protein Sistatin-C Renal tubuler epitelyal antijen Enzimler N-asetil-b-glukosaminidaz Alanine aminopeptidaz Alkalen fosfataz Laktat dehidrogenaz g/n glutatyon –S-transferaz G-glutamil transpeptidaz Bazıları ümit vaat ediyor Ancak genel kullanımları için kanıtlar henüz yetersiz (β2-microglobulin, α1-microglobulin, adenosine deaminase binding protein, retinol binding protein, cystatin C and renal tubular epithelial antigen-1), enzymes (N-acetyl-β-glucosaminidase, alanine aminopeptidase, alkaline phosphatase, lactate dehydrogenase, α/π-glutathione-S-transferase, and γ-glutamyl transpeptidase), cytokines (platelet-activating factor and IL-18)and other biomarkers (kidney injury molecule-1 and Na/H exchanger isoform-3). Increased levels of platelet-activating factor, IL-18 and Na/H exchanger isoform-3 were detected early in septic AKI and predicted kidney failure. Several additional biomarkers were evident early in AKI, but their diagnostic value in sepsis remains unknown. In one study, IL-18 excretion was greater in septic than in nonseptic AKI. IL-18 also predicted deterioration in kidney function, with increased values preceding clinically significant kidney failure by 24 to 48 hours. Detection of cystatin C, α1-microglobulin and IL-18 predicted need for renal replacement therapy (RRT). The authors concluded that that selected biomarkers may be promising in early detection of AKI in sepsis and may have value for predicting subsequent deterioration in kidney function. scientific basis for use of urinary biochemistry, indices and microscopy in patients with septic AKI is weak. More research is required to describe the accuracy, pattern and time course of these parameters in patients with septic AKI.

12

13 AKI’ye neden olan başlıca kategorilerin insidansıPrerenal azotemi Böbreğin akut hipoperfüzyonuna bağlı 55-60% Intrinsic renal azotemi Renal parankime ait akut hastalıklar -Büyük böbrek damarı hast. -Küçük böbrek damarları ve glomeruler hast. -ATN (iskemik ve toksik) -Tubulo-interestisyel hast. -Intratubular obstrüksiyon 35-40% *>90%* Postrenal azotemi İdrar yollarının akut obstrüksiyonu <5%

14 PRE-RENAL nedenler En sık neden Renal perfüzyonda azalmaİntravasküler volümde azalma Dehidrasyon/kanama/diyare/ poliuri/ 3. boşluğa sıvı kaybı Systemik vazodilatasyon Sepsis /anafilaksi/ anestezi Kardiyak output’un azalması KYşok/masif pulmoner emboli/ perikard tamponadı Yeterince uzun sürdüğünde  Renal ARF

15 Acute tubular necrosis

16 ATN Seyri ve Prognozu Başlangıç fazı İdame fazı iyileşmeİskemik veya nefrotoksik ajanlar Parenkim hasarı başlıyor; henüz oturmamış İdame fazı Parenkim hasarı oturmuş GFR 5-10ml/min İdrar çıkışı en azında 2-3 hafta sürer iyileşme İdrar çıkışı giderek artar

17 Renal hasar riskini artıran faktörlerİleri yaş Volume eksikliği Diyabetes Mellitus Hipertansiyon Diuretic kullanımı Önceki kardiyak ya da renal yetersizlik Proteinuri Miyelom

18 RENAL nedenler Renal parankimal nedenler Hızlı ilerleyici GNPostinfectious / Henoch Schonlein purpura Idyopatik Hızlı İlerleyici GN Pulmorenal sendromlar/SLE/IgA Akut interstisyel nefrit İlaca bağlı Nefrotoksinlere bağlı Vankomisin /aminoglikozidler /NSAID/Amfoterisin Akut piyelonefrit

19 POST-RENAL nedenler En az sık ama önemliİdrar akımının bilateral tıkanması Bilateral renal pelvis –ureterler –measne-uretral Benign prostat hipertrofi Servikal ya da over Ca Taşlar (özellikle soliter böbrekte) DM’da Papiller nekroz Nadiren pıhtıya bağlı

20 Hastaya Yaklaşım Öykü ve Fizik MuayeneHasta takip çizelgesi, ilaçlar, uygulanan işlemler ve işlemler sırasındaki hemodinamik İdrar analizi, idrar mikroskopisi silendirler, (eosinophils) İdrar Na’u Uriner sistem görüntülemesi: US, Mag-3 scan, Retrograde piyelogram KBY belirteçleri iPTH, böbrek boyutu<9cm, anemi, ↑ phosphate, ↓bikarb Renal biyopsi

21 RPGN’de İdrar sedimenti bulguları

22 Ayırıcı tanıda Laboratuvar bulgularıPre-renal: BUN/kreatinin > 20/1 İdrar Na < 20 Normal idrar sedimenti Post renal: Normal idrar sediment / hematuri/piyuri Ultrason bulguları Renal nedenler: İdrar sedimenti bulguları

23 AKI Tedavisi Pre-renal nedenler: Renal nedenler: Postrenal:Sıvı/kan desteği Renal nedenler: GN- immunsupresifler ve /plazmaferez AIN- Nedeni kes Nefrotoksik ajan- kes ATN- sıvı ve elektrolit dengesi/destek tedavisi Postrenal: Üriner kateterizasyon Obstrüksiyonun ortadan kaldırılması

24 AKI tedavisi Tedavi büyük oranda destekleyiciHalen kanıtlanmış bir farmakolojik tedavisi yok: Dopamine: yararı yok Renal Replasman tedavisi ciddi AKI’li hastaların bir bölümünde tedavinin en önemli bölümünü oluşturur Nephron Clin Pract 2009;112:c222-c229

25 AKI-EPİDEMİYOLOJİ Çalışma sırasında AKI insidansı↑ : %2.8/seneAvustralya’da 20 YBÜ ’e kabul edilen tüm hastalar: 91254 hasta ; 4745 AKI olgusunun analizi : İnsidans %5.2 Çalışma sırasında AKI insidansı↑ : %2.8/sene Hastane mortalitesi AKI (+) %42.7; AKI(-) %13.4 YBÜ’deki AKI hastaları giderek daha Yaşlı Ko-morbid hastalıklı Sepsis insidansı fazla Daha ağır organ yetmezlikli An Australian survey of data of all adult admissions to 20 Australian ICUs for 24 hours or more from 1 January 1996 to 31 December 2005 was conducted to assess trends in incidence and mortality for ICU admissions associated with early AKI [23]. The authors analyzed 91,254 patient admissions, including 4,754 cases of AKI, for an estimated crude cumulative incidence of 5.2%. The incidence of AKI increased during the study period, with an estimated annual increment of 2.8%. The crude hospital mortality was significantly higher in patients with AKI than in those without it (42.7% versus 13.4%). There was also a decrease in AKI crude mortality (annual percentage change: -3.4%), however, which was not observed in patients without AKI. After covariate adjustment, AKI remained associated with a higher mortality (odds ratio = 1.23; P < 0.001), but there was a declining trend in the odds ratio for hospital mortality. Such retrospective studies and many other observational ones suggest that critically ill patients with AKI are increasingly older, have more co-morbid disease, have a higher incidence of sepsis, and have greater severity of illness and organ failure [24]. It is possible, however, that outcomes in patients treated about 10 years ago is not meaningful when compared with prospective data from multinational and multicentre assessment of patients who are all critically ill, treated in an ICU, and typically receiving mechanical ventilation and vasopressor therapy [25]. Despite the much greater severity of illness in patients treated today,the mortality of AKI has not increased and has perhaps slightly decreased, the duration of treatment has clearly decreased in terms of need for dialysis; also, the time spent in the ICU and in hospital, and artificial renal support techniques have also changed markedly (significant findings have been reported for the subgroup of AKI patients who have suffered trauma [23]). It is likely, hence, that the 50% to 60% crude mortality associated with AKI will not change dramatically in the coming years, because as therapeutic (and diagnostic) capabilities improve, the health care system will admit and treat progressively sicker patients with AKI. Comparisons that do not take into account this continuing adjustment and that do not appreciate the continuing change in illness severity will present a misleading picture of achievements associated with improvements in technology and medications. AKI MORTALİTESİNİN ARTTIĞI SÖYLENEMEZ

26 Critical Care 2008, 12:R144