3 GFR Düşmeden BUN ve Kreatinin Yükselme Nedenleri Üre sentezinde GİS kanamaKortikosteroidlerTetrasiklinProtein alımında artışAmino asit uygulanmasıKatabolizmada artış ve ateşli hastalıkKreatinin yapımında RabdomiyolizTubuler Kr sekresyonunda CimetidineTrimethoprim
4 ABY AKI Artan Böbrek Hasarı (Acute Kidney Injury) (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 .
6 AKI: Tanımı Renal işlevde ani (48 saat içinde) bozulma AKIN redefined AKI as ‘An abrupt (within 48 hours) reduction in kidney function currently defined as anabsolute increase in serum creatinine of more than or equal to 0.3 mg/dl, a percentage increase in serum creatinine of morethan or equal to 50% (1.5-fold from baseline), or a reduction in urine output (documented oliguria of less than 0.5 ml/kgper hour for more than six hours).’ Several specifications were provided by the workgroup to this updated definition andwere followed by a new staged classification of AKI severitySerum BUN ve Kreatinin > 0.3mg/dl ve/veya %50 (1.5 x Bazal)İdrar çıkışında azalma <0.5ml/kg/saat > 6 saat
7 AKI Klasifikasyon/Evreleme sistemi Sınıf/EvreKr Kriteriİdrar kriteriRIFLERiskInjuryFailurex 1.5 /GFR↓>%25x 2 / GFR↓>%50x 3 / GFR↓>%75; Kr>4mg/dl + en az akut 0.5mg/dl↑<0.5ml/kg/saat -6saat<0.5ml/kg/saat -12 saatAnuri- 12 saatAKINEvre 1Evre 2Evre 3>0.3 mg/dl veyaBazal x 1.5-2Bazal x 2-3Bazal x > 3 veyaKr>4mg/dl + en az akut 0.5mg/dl↑RRT gereksinimi<0.3 ml/kg/saat -24 saat veya anuri-12 saat
8 AKI (+) AKI (-) 45.8 %16.4 Mortalite (%) RIFLE Çalışmasının Meta analiziKidney 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 . 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%16.4N=120AKINKriterleriCrit Care Med 2008,36:
9 AKI Bio-belirteçleri var mı? SitokinlerPlatelet aktive edici faktörIL-18DiğerleriKidney injury molekül-1Na/H exchanger isoform-3GenlerNötrofil gelatinaz associated lipocalin (NGAL)Düşük molekül ağırlıklı proteinlerB2-mikroglobulinA1-mikroglobulinAdenozin deaminaz bağlayıcı proteinSistatin-CRenal tubuler epitelyal antijenEnzimlerN-asetil-b-glukosaminidazAlanine aminopeptidazAlkalen fosfatazLaktat dehidrogenazg/n glutatyon –S-transferazG-glutamil transpeptidazBazıları ümit vaatediyorAncak genelkullanımlarıiçin kanıtlarhenüz 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, alanineaminopeptidase, 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-microglobulinand 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.
14 İLACA İKİNCİL ABY Akut Tubuler Hasar Otoregülasyon bozukluğu AminoglikozidlerBazı sefalosporinlerAmfoterisin BVancomycinOtoregülasyon bozukluğuACE inhibitörleriAII reseptör blokerleriNSAIDRadyokontrast ajanlarAkut Interstisyel nefritTüm ilaçlar
15 ‘Kronik’ zeminde ‘Akut’ Olgusu KBY zemininde araya giren ek bir sorun nedeniyle renal işlevde Akut kötüleşmeHipovolemiNefrotoksik ilaç kullanımıInfeksiyonObstrüksiyonKalp yetersizliğiAkselere hipertansiyon
17 Renal İşlev Nasıl Değerlendirilmeli ? Kreatinin klirensi24 saatlik idrar toplanarakCockroft ve Gault formülüne göre:(140-yaş) x Ağırlık72 X PCr (mg/dl)(Erkek)Kadın:x 0.8
18 İlaç Dozunun Ayarlanması İdrar çıkışı <400ml/gün ise, serum kreatinindeğeri ne olursa olsun, klirens <10ml/dk>60 yaşta klirens 10-50ml/dkOLARAK KABUL EDİLMELİDİROral alımda biyoyararlanım düşer i.v. yol tercih edilmeli Proteine bağlanma oranı azalır İlaç toksisite riski artar Dağılım hacmi etkilenir Metabolizması etkilenir Atılımı etkilenir. Böbrek yetersizliğinde ilaç kullanım rehberlerinden yararlanılmalıdırYÜKLEME DOZU DEĞİŞMEZİDAME DOZU:DOZ AZALTILABİLİRDOZ ARASI UZATILABİLİR
19 YBÜ’DE AKI’YE KONSERVATİF YAKLAŞIM : ÖNLENMESİ HİPOVOLEMİDEN KAÇINILMASIRADYOKONTRASTTAN KAÇINILMASI VE/VEYA PROFİLAKTİK ÖNLEMLERİLAÇ UYGULAMALARINDA DOZLARA VE NEFROTOKSİK AJANLARA DİKKATHEMODİNAMİK DESTEK
21 YBÜ’DE ABY’NE KONSERVATİF YAKLAŞIM-BESLENME KALORİ VE BESİN GEREKSİNİMİ DİĞER YBÜ HASTALARINDAN FARKLI DEĞİL35 KCAL/kg/GÜN g/kg/gün proteinG:L=70/30RRT SIRASINDA EK OLARAK 0.2g/kg/gün PROTEİN ALMALILARENTERAL YOL TERCİH EDİLMELİESANSİYEL-NONESANSİYEL AA AYRIMI GEREKLİ DEĞİLVOLÜM KISITLAMASI ÖNEMLİPatients with AKI often have PEW (preexisting and/or hospital acquired), which represents a major negative prognostic factor. Nutritional support is frequently required in the form of parenteral and/or enteral nutrition, even though no formal demonstration exists concerning its positive effect on major outcomes. The primary goals of nutritional support in AKI are basicallythe same as those suggested for critically ill patients having normal renal function. Patients with AKI on RRT should receive at least 1.5 g/kg per day of proteins, and not more than 30 kcal nonprotein calories or 1.3BEE calculated by the Harris–Benedict equation, with lipid supply representing about 30–35% of energy. To compensate for amino acid losses during RRT, protein supply should be increased by some 0.2 g/kg per day. Even in patients with AKI, the enteral route should represent the preferred route for nutrient delivery; however, parenteral nutrition is often required to fulfill nutritional requirements. A close integration between nutritional support and RRT is needed in AKI, with the aim of carefully tailoring both therapies on patients’ changing needs.RRT BESLENMENİN DAHASERBEST OLMASINI SAĞLAR
22 Düşük Doz Dopamin ve Furosemide: ASILSIZ EFSANE Crit Care Med 1981; 9: ; Parker ve ark.Crit Care Med 1982;10: Davis ve arkIntensive Care Med 1996;22: ; Lerm T ve arkAnesth Analg 1998; 86: 3-8 ; Lema G ve ark(+)Kidney Int 1996; 50: 4-14; Denton ve ark.N Engl J Med 1996;334: ; Thadhani ve arkKidney Int 1998; 54: ; Star RAJ Am Soc Nephrol 2000; 11:97-104,Lassnigg ve ark.Lancet December 23/30, 2000; 356: ;ANZIC CTGJAMA November 27, 2002; 288: ;Mehta ve ark.JAMA November 27,2002; 288: ;Lameire ve ark..(-)
23 Lack of Renoprotective Effects of Dopamine and Furosemide During Cardiac SurgeryLassnigg ve ark. J Am Soc Nephrol 11:97-104, 2000
24 YBÜ’DE AKI DAHA ÇOK MOYS’NUN PARÇASIDIR Kidney Int 1998;53: S16-S24
28 Ciddi AKI %6.3 %83.7 %47.3 %63.9 Cerrahi nedenli olamayan N=17 326 SepsisThis study pools data from the UK Intensive Care National Audit and Research Center (ICNARC) Case Mix Programme (CMP) to evaluate the case mix, outcome andactivity for 17,326 patients with severe acute kidney injury (AKI) occurring during the first 24 hours of admission to intensive care units (ICU). Results Severe AKI occurred in 17,326 out of 276,731 admissions (6.3%). The source of admission was nonsurgical in 83.7%. Sepsis was present in 47.3% and AKI was nonoliguric in 63.9% of cases. Admission to ICU with severe AKI accounted for 9.3% of all ICU bed-days. Oliguric AKI was associated with longer length of stay for survivors and shorter length of stay for nonsurvivors compared with nonoliguric AKI. Oliguric AKI was associated with significantly greater ICU and hospital mortality (55.8% and 77.3%, respectively) compared with nonoliguric AKI (33.4% and 49.3%, respectively). Surgery during the 1week before admission or during the first week in the CMP unitwas associated with decreased odds of mortality. UK APACHE II and the Mehta scores under-predicted the number of deaths,whereas SHARF T0 and SHARF II0 over-predicted the number of deaths.%63.9Non-oligurikYBU Yatak günlerinin %9.3’ü ciddi AKICritical Care 2008, 12:S2
29 Skorlama sistemleri mükemmel değil, ölüm öngörüsü ↓ veya ↑ çıkıyor AKIOligurikNon-oligurikYBÜ mortalitesi (%)55.833.4Hastane (%)77.349.3N=17 326Oliguric AKI was associated with longer length of stay for survivors and shorter length of stay for nonsurvivors compared with nonoliguric AKI. Oliguric AKI was associated with significantly greater ICU and hospital mortality (55.8% and 77.3%, respectively) compared with nonoliguric AKI (33.4% and 49.3%, respectively). Surgery during the 1week before admission or during the first week in the CMP unit was associated with decreased odds of mortality. UK APACHE II and the Mehta scores under-predicted the number of deaths,whereas SHARF T0 and SHARF II0 over-predicted the number of deaths.Skorlama sistemleri mükemmel değil,ölüm öngörüsü ↓ veya ↑ çıkıyorCritical Care 2008, 12:S2
30 HATIRLAMAYA DEĞER GERÇEKLER YBÜ’DE ABY:HATIRLAMAYA DEĞER GERÇEKLERABY hastalarının başka organ sistemleri de hastadırABY’de RRT önemli ancak yaşam kurtarma açısından yetersizdirAmacımız, böbrek yetersizliğine bağlı, komplikasyonları, ölümü ve tedaviye bağlı ölümleri önlemektir
31 Ne zaman diyaliz? Oligüri-anüri Kr progresif yükselme 4-5mg/dl’ye ulaştığındaBUN değerleri >100 mg/dlAsidozHiperkalemiHipervolemi
32 YBÜ’DE RENAL REPLASMAN TEDAVİSİ IHD- Intermittan HemodiyalizGünaşırıHergünCRRT-Sürekli Renal Replasman TedavisiCVVHDFCVVHFSLED- Sustained Low Efficiency DialysisThese novel techniques ofrenal substitution therapy have permitted a conceptualshift from renal ‘‘replacement’’ to renal ‘‘support’’ therapies(4), whereby the strategies to treat AKI havebecome an integral part of overall critically ill patientmanagement, with ‘‘renal’’ and ‘‘nonrenal’’ applicationssuch as sepsis and acute respiratory distress syndrome(ARDS).
34 ABY’de RRT Diyalizin zamanlaması ve dozu Diyalizör biyo-uyumluluğu Diyalizör performansıDiyaliz tipi(CRRT vs IHD vs SLED vs PD)
35 Fig. 1. Modalities of continuous renal replacement therapies (CRRT) Fig. 1. Modalities of continuous renal replacement therapies (CRRT). Techniques available today for renal replacement in the intensive care unit. CAVH, continuous arterio–venous hemofiltration; CHP, continuous hemoperfusion; CPFA, plasmafiltration coupled with adsorption; CPF-PE, continuous plasmafiltration-plasma exchange; CVVH, continuous veno-venous hemofiltration; CVVHD, continuous veno-venous hemodialysis; CVVHDF, continuous veno-venous hemodiafiltration; CVVHDF, continuous high-flux dialysis; D, dialysate;HVVF, high-volume hemofiltration; K, clearance; Pf, plasmafiltrate flow; Qb, blood flow; Qd, dialysate flow; Qf, ultrafiltration rate; R,replacement; SCUF, slow continuous ultrafiltration; SLED, sustained low efficiency daily dialysis; UFC, ultrafiltration control system.
36 DİYALİZ REÇETELENMESİNİN İNCE AYARI Vasküler giriş yoluVenöz çift lümenli kateterlerJuguler /femoralMembran tipiGeçirgenlik-biyo-uyumDiyalizat elektrolit içeriğiNa-K-Ca-HCO3Diyalizat sıvısının saflığıDiyaliz makinesi monitorizasyonuAntikoagülasyon
37 Since the original formulation of the dose concept for renal replacement therapy more than 30 years ago  and the establishment of a link between dose and clinical outcome [2,3], individualized patient dosing based on urea clearance is now routine in end-stage renal disease (ESRD) patients. More recently, similar principles have been applied to critically ill patients with acute kidney injury (AKI) treated both with continuous renal replacement therapy (CRRT) and with intermittent modalities.Using the normalized effluent rate as a dose surrogate in postdilution continuous venovenous hemofiltration, Ronco and colleagues reported higher survival in patients receiving a dose of 35 or 45 ml/hour/kg than in patients receiving a dose of 20 ml/hour/kg .
38 Çok merkezli, randomize kontrollü CRRT vs IHDÇok merkezli, randomize kontrollü**n=16665.559.556.650.647.641.5* p<0.02Mehta ve ark. Kidney Int 2001;60:
39 IHD CRRT p %Male 68.3 83.3 <0.023 %KC yetersiz. 29.3 42.9 <0.05 Randomize olmasına rağmen hasta dağılımı IHD lehineIHDCRRTp%Male68.383.3<0.023%KC yetersiz.29.342.9<0.05APACHE III87.796.4<0.045Mehta ve ark. Kidney Int 2001;60:
40 AKI (+) YBÜ Hastası – en az 1 böbrek dışı organ tutulumu veya sepsis Primer sonlanım noktası – 60 günde tüm nedenli ölümWe randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensivetreatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatmentstrategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. ResultsBaseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P = 0.47). There was no significant difference between the two groups in the duration of renal replacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. Conclusions Intensive renal support in critically ill patients with acute kidney injury did not decreasemortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapyat 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT )Yoğun RRTAz Yoğun RRTHemodinamik stabil→ IHDHemodinamik stabil olmayan → CVVHD/SLED
43 Ciddi eleştiriler getiriyor. Critical Care 2008, 12:308
44 CRRT ‘deki membranlar Yüksek geçirgenlikli Biyouyumlu Su Küçük ve orta moleküler ağırlıklı solutlerBiyouyumluThe main feature of convective treatments is the use of high-flux membranes, characterized by high permeability for water as well as low- and middle-molecular weight solutes (in the range of 1000–12,000Daltons) andhigh ‘‘biocompatibility.’’ It is a widespread opinion that convective treatments like high-flux hemodialysis, hemodiafiltration,and hemofiltration offer a clinical advantage over standard dialysis when considering physiological outcomes. The crucial point is that up until now, studies have not been able to demonstrate superiority of these techniques on morbidity, mortality, and quality of life (6,13–18).
46 Sitokin Uzaklaştırılması Sürekli Tedavi ileSitokin UzaklaştırılmasıCytokine Removal during Continuous Hemofiltration in Septic PatientsDE VRIESE*, FRANCIS A. COLARDYN , JAN J. PHILIPPÉ , RAYMOND C. VANHOLDER*, JOHAN H. DE SUTTER and NORBERT H. LAMEIRE*JASN, 10:4; : 1999
47 IHD vs CRRT Deneyim çok Modern makinalarla Kontrollü UFOnline- diyalizatIntradiyalitik solüt klirensi Tedavi süresi kısaHemodinamik instabiliteye yol açabilirUltrafiltrasyona tolerans daha iyiSürekli Azotemi kontrolüPahalıTedavi süresi devamlıDevamlı antikoagülasyon gerekli
48 SLED CRRT ile aynı tedavi amaçlarına sahip IHD gibi aralıklı tedavi olanağı sağlıyorYavaş diyalizle başlanır:Qb=150ml/dkQd= ml/dkUF hızı= max:350 ml/saat
49 SLEDD:HEMODİNAMİK STABİLİTE Kumar ve ark. AJKD:2000:36:
52 YBÜ’de Ne Tip RRT seçilmeli? IHDDiürez>500ml/günTek organ yeters.IHD + UFCVVHOligo-anuriaTek organ yeters.Tek organ yetersizliğiUGR CVVHHer gün IHDSLEDDiürez>500 mlMOYIn practice, hemodynamic stability of the critically ill patient is the main determinant of the choice of dialysis modality (5) (Table 3). In addition to the patient’s hemodynamic stability, the choice between the various RRTs rests on solute clearance goals, volume control, and anticoagulation (Table 4).Volümlü CVVHSLED saatOligo-anuriaMOYKB stabil değilUGR
53 Ciddi metabolik asidoz AmaçHemodinamiTercih edilen RRTSıvı ÇekilmesiStabilStabil değilAralıklı izole UFYavaş sürekli UFÜre klirensiIHDCRRTCiddi hiperkalemiStabil / stabil değilCiddi metabolik asidozCiddi HiperfosfatemiStabil/stabil değil
54 AKI-EPİDEMİYOLOJİ Çalışma sırasında AKI insidansı↑ : %2.8/sene Avustralya’da 20 YBÜ ’e kabul edilen tüm hastalar:91254 hasta ; 4745 AKI olgusunun analizi : İnsidans %5.2Çalışma sırasında AKI insidansı↑ : %2.8/seneHastane mortalitesi AKI (+) %42.7; AKI(-) %13.4YBÜ’deki AKI hastaları giderek dahaYaşlıKo-morbid hastalıklıSepsis insidansı fazlaDaha ağır organ yetmezlikliAn Australian survey of data of all adult admissions to 20 Australian ICUs for 24 hours or more from 1 January 1996 to31 December 2005 was conducted to assess trends in incidence and mortality for ICU admissions associated withearly AKI . The authors analyzed 91,254 patient admissions, including 4,754 cases of AKI, for an estimatedcrude 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 observationalones suggest that critically ill patients with AKI are increasingly older, have more co-morbid disease, have ahigher incidence of sepsis, and have greater severity of illness and organ failure . It is possible, however, thatoutcomes 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 . 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 beenreported for the subgroup of AKI patients who have sufferedtrauma ). It is likely, hence, that the 50% to 60% crudemortality associated with AKI will not change dramatically inthe coming years, because as therapeutic (and diagnostic)capabilities improve, the health care system will admit andtreat progressively sicker patients with AKI. Comparisons thatdo not take into account this continuing adjustment and thatdo not appreciate the continuing change in illness severitywill present a misleading picture of achievements associatedwith improvements in technology and medications.AKI MORTALİTESİNİN ARTTIĞI SÖYLENEMEZ
55 SONUÇ ABY gelişmemesi için önlemlerin alınması gerekli Özellikle riskli hasta gruplarının belirlenmesi önemliABY’de Dopamin ve furosemid kullanımını destekleyen kanıt yokRRT seçimi ünite koşulları ve hasta gereksinimine göre belirlenmeli