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7-1-2. Acute kidney injury. Dmitriy Zverev (eng)

7-1-2. Acute kidney injury. Dmitriy Zverev (eng)






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    7-1-2. Acute kidney injury. Dmitriy Zverev (eng) 7-1-2. Acute kidney injury. Dmitriy Zverev (eng) Presentation Transcript

    • Acute kidney injury: definition, biomarkers, epidemiology, early diagnosis. Renal replacement therapy in children Dmitry Zverev (Moscow, Russia)
    • Definition  “Sudden loss of renal function resulting in the loss of the kidneys’ ability to regulate electrolyte and fluid homeostasis”
    • Diagnostic criteria for AKI  urine output  Serum creatinine levels   increase in serum creatinine (>50% above baseline level) and, in most cases, a concomitant reduction in urine output (less than 0.5–1 ml/kg per hour)
    • Pediatric Modified RIFLEdefinition Pediatric Modified RIFLE Criteria CrCl Risk GFR decrease by 25% Injury GFR decrease by 50% Failure GFR decrease by 75% or 2 GFR<35ml/min/1.73m Loss Urine output <0.5ml/kg/hour for8 hours <0.5ml/kg/hour for16 hours Persistent ARF > 4 weeks End stage <0.3 ml/kg/hour for24 hours or anuric for 12 hours End Stage Renal Disease (>3 months) Ackan-Arikan et al: Kid Int 2007
    • Calculating GFR using Schwartz formula GFR = height (cm) X К/sCr (mg/dl) К - constant k = 0.33 premature neonates k = 0.45 neonates and infants, under 1 y.o. k = 0.55 children, under 13 y.o. and girls, over 13 y.o k = 0.70 boys, over 13 y.o. • • mg/dl х 88 = mkmol/l mkmol/l х 0,0113= mg/dl
    • GFR in children age GFR 1 - 2 days 20.8 ± 5.0 4 - 14 days 36.8 ± 7.2 15 – 19 days 46.9 ± 12.5 1 – 3 months 60.4 ± 17.4 4 – 6 months 87.4 ± 22.3 7 – 12 months 96.2 ± 12.2 1 – 2 years 105.2 ± 17.3 3 – 8 years 111.2 ± 18.5 9 – 12 years 116.6 ± 18.1 13 – 15 years 117.2 ± 16.1 G.Schwarts. Glomerular filtration rate measurement and estimation in kidney disease. Pediatric Nephrol (2007) 22:1839-1848
    • Creatinine disadvantages as AKI marker  Plasma Creatinine – measure of function (not injury)  More than 50% nephrons must be compromised for SCr level changes to be evident  Therefore, SCr is at best a late marker of significant renal dysfunction
    • Characteristics of an Ideal Biomarker 1. Biomarker have to be an active substance that is immediately excreted by the damaged cells of the kidneys 2. Has a high sensitivity and specificity 3. Be available for direct determination in urine or blood 4. Have an acceptable "price - quality"
    • Biomarkers of AKI (Devarajan P: Emerging urinary biomarkers in the diagnosis of acute kidney injury. Expert Opin Med Diagn 2008, 2:387-398.)      neutrophil gelatinase-associated lipocalin (NGAL) cystatin С (CysC) kidney injury molecule-1 (KIM-1) interleukin 18 (IL-18), liver-type fatty acid-binding protein(L-FABP)
    • NGAL(Neutrophil gelatinase-associated lipocalin)   a 25-kD protein of the lipocalin superfamily, is expressed by kidney tubules epithelium First time as a marker of AKI was described in 2003 [Mishra J. et al] The role of NGAL as a biomarker of kidney damage is confirmed by experimental studies on various models of critical states [Haase-Fielitz A., Bellomo R., Devarajanet P. 2009]  Critically ill patients in ICUs have NGAL level ≥155 nmol/l, indicating AKI (sensitivity 82%, specificity 97%) [Constantin J.M. et  al.2010 De Geus H.R., 2011 . Haase-Fielitz 2009 ]
    • Cystatin C Cystatin С (protease inhibitor) is filtrated in glomerulus in the kidneys, completely reabsorbed and isn’t secreted in the tubules  Consequently it is a marker of glomerular filtration rate (GFR)  If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise  Cystatin C levels in AKI become higher on 24-48 hours earlier than creatinine levels  Disadvantages: high cost 
    • Kidney injury molecule-1 (KIM-1)  Transmembrane protein  Not detected in blood and urine normally  Expression is markedly up-regulated in the damaged proximal tubules  Disadvantages: • doesn’t make prediction • high cost
    • Interleukin 18 (IL-18)  Proinflammatory cytokine, produced by the distal tubules, collecting tubules of the kidneys  Urinary IL-18 is a useful biomarker of AKI  IL-18 secretion distinctly increases in AKI  Disadvantages: • low sensitivity • low specificity
    •  Nowadays biomarkers can’t provide the stratification of ungraded AKI  Validation of these biomarker studies needs to be performed in different critically ill populations
    • The incidence of AKI requiring RRT Prevalence on 100 thousand. 227 cases for 84-91 years (Yorkshire UK) 19.7 17.2 4 5.9 1.5 adults Children Newborn s 1-4 years 5-15 years Adapted from Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Askenazi DJ, Goldstein SL. Pediatr Nephrol. 2009 Feb;24(2):265-74. Epub 2008 Dec 10.
    • Etiology of AKI Prerenal (renal hypoperfusion) Renal (intrinsic) Postrenal Glomerulonephritis Low intravascular volume Hemorrhage/bleeding Severe dehydration Third-space losses Decreased effective circulating volume Cardiac dysfunction Renal artery obstruction Sepsis rapidly progressive, immune-mediated diseases HUS Cortical necrosis, renal vein/artery thrombosis, DIC  Acute interstitial nephritis: Infection/pyelonephritis Acute tubular necrosis: hypoxic/ischemic injury, drug-induced Tumor lysis syndrome Urethral obstruction: posterior urethral valves in neonates; Obstruction kidney urinary tract: (ureteral–pelvic unction, ureteral stenosis, uretero–vesical unction), stones, mass
    • Management of AKI  should be monitoring and laboratory controlling  require special methods of intensive therapy in the ICU  an optimal microclimate around the child  conducted simultaneously with the diagnostic activities
    • Management of AKI  At the beginning rapid volume replacement should be undertaken at the same time for final diagnosis (Crystalloid solution 20 ml/kg normal saline or 5% glucose for 20-30 minutes)  fresh frozen plasma could be used as a starting solution in sepsis, peritonitis and severe surgical pathology (it has a long-lasting effect on hemodynamics and stays in the circulatory longer)
    • Management of AKI No diuresis ensues after fluid administra-tion Normal cardiac output (normal renal perfusion) Renal intrinsic injury Dialysis (attempt fast) improvement of renal perfusion (by dopamine, a rapid increase in blood volume, colloids transfusion) may lead to rupture of blood vessels in the germinal matrix and intraventricular hemorrhage development 
    • AKI etiology in children and mortality DGKB St.Vladimir (2002-12гг.) AKI etiology HUS and TTP MODS GN, systemic diseases AKI in newborns AKI of various etiology Amount of children n = 326 219 (67,8%) Mortality n =53(16,3%) 11(5%) 24(7,4%) 14 (58,3%) 25 2 38(12,7%) 23 (60%) 19 3
    • AKI etiology in children AKI etiology DGKB St.Vladimir Moscow hospitals years 2002-10 2012 2012 Children with AKI 276 50 200 HUS 188(68%) 29(58%) 31(15,5%) MODS, шок, sepsis, cardiosurgery, HF 50 13 169
    • The main cause of AKI Preschool age School age HUS GN, shock, TTP
    • Hemolytic uremic syndrome Is defined by a triad of symptoms: - Hemolytic anemia - Thrombocytopenia - Azotemia
    • Pathological basis of HUS - thrombotic microangiopathy affecting: KIDNEYS brain lungs bowel liver heart
    • Typical HUS Escherichia Coli O157:H7 O111:H8 O103:H2 O121 O145 O26 O113 Shiga like toxin, type 1 Shiga like toxin, type 2 B B B AB B Shigella dysenteria Serotype 1 Shiga-toxin, тип 1 Brooks J.T. et al., (2004) Sonntag A.K. et al., (2004) Noris and Remuzzi,, JASN, 16:1035 (2005)
    • Infection sources Escherichia coli O157:H7 - meat - dairy products - fruit juices - potable water - pets - water in open-air reservoirs and swimming pools
    • Typical HUS occurrence North America 2-3 cases per 100000 children under 5 years old, Argentina 10 times higher Moscow – 4 cases Moscow region 4-5 cases per 100000 children under 5 years old
    • Pediatric nephrology (2008)23:1749-1760
    • The earlier dialysisthe better prognosis of HUS
    • HUS outcomes  Mortality during the acute phase 2-6%  ESRF development 1-2%  Development ESRF during first 5 years 5-7%  Development ESRF during 10-15 years 10-15% more
    • Thrombotic thrombocytopenic purpura  TTP is characterized by microangiopathic hemolysis and platelet aggregation in hyaline thrombi, with no activation of the coagulation system  This leads to partial occlusion of blood vessels associated with excessive proliferation of endothelial cells  Kidney, brain, heart, pancreas, spleen, and adrenals endothelium are suffered
    • Thrombotic thrombocytopenic purpura  The reason of familial and aquired idiopatic TTP is insufficient destruction of unusually large multimers of von Willebrand factor, which are destroyed by metalloproteinase ADAMTS-13  lack of protease activity caused by either its serious shortage or production of autoantibodies
    • Management of TTP  Plasmapheresis became the treatment of choice for TTP in mid-80s  Supply of ADAMTS-13 and removal of anti- ADAMTS-13 autoantibodies and unusually large multimers of von Willebrand factor make provision the effect of plasmapheresis  Pulse therapy with Metipred
    • The mechanism of AKI in GN Edema of interstitial tissue, increasing of hydrostatic pressure in the proximal tubule and the Bowman's capsule, which leads to reduction of filtrational pressure and glomerular filtration  protein mass and blood clots occlude tubules  fast-growing proliferation of glomerular capillary loops with compression and/or tubulointerstitial changes  vasoactive substances and cytokines release from monocytes and other cells 
    • Management of GN with AKI  RRT when indicated  Symptomatic therapy (treatment of neurological, cardiovascular and respiratory disorders)  Pathogenetic therapy of GN in the early stages of the disease (corticosteroids, alkylating agents, plasmapheresis)
    • Indications for emergency dialysis   ANURIA > 1 day Complicated OLIGURIA: • • • • • • • hyperhydration with pulmonary edema and/or respiratory failure, uncontrolled hypertension disorders of the central nervous system heart failure hyperkalaemia > 7.5 mmol/l decompensated metabolic acidosis increase of creatinine level > 120 mkmol/day ensuring adequate child nutrition and infusion therapy
    • HD? PD? CVVHDF?
    • Hemodialysis in children (basic practical guidelines European Pediatric Dialysis Working Group, 2005) 1. Department of HD should be located in a children's hospital with multi-disciplinary experts available 2. Water quality: adequate biochemical composition, the absence of microbiological contamination 3. A hemodialysis machine: volume control UF, a single needle connected option 4. Hemodiafiltration option for maximum efficiency
    • Hemodialysis Advantages The high speed of purification and UF The ability to adjust the composition of the dialysate Disadvantages •Difficulties of vascular access to ensure an adequate blood flow in child weighing < 5 kg •Large extracorporeal volume •Hypotension episodes during UF •Cardiovascular insufficiency •Risk of bleeding assosiated with systemic anticoagulation •Fluid limitation between dialysis; •Disequilibrium syndrome
    • Peritoneal dialysis 1. Dialysis solution 2,3. Containers measuring cylinders 4. Peritoneal catheter 5. Container for the drained solution 6. Clip Begins from 10 ml/kg Exposition 0,5 – 1 hour
    • PD in infants with extremely low birth weight
    • Advantages of PD       Continuing process of blood purification and UF; Implantation of peritoneal catheter and PD conducting is a simple procedure, possible in hospital PD does not have a marked influence on hemodynamics, it can be used in patients with hypotension and even in patients with multiple organ failure Isn’t required providing of vascular access, anticoagulation therapy PD solution - a source of extra calories Low cost of treatment
    • Disadvantages of PD  low nitrogenous wastes, blood electrolytes clearance, small rate of UF  PD conducting is impossible in patients with purulent peritonitis, in the early postoperative period after laparotomy, with leaking abdominal  cautious and limited using of PD in patients with concomitant respiratory failure
    • Surgical complications during PD 1. Catheter setting and operation dialysate draining (14,1%), drainage disruption(4.5%), internal organs wounding, bleeding 2. Infectious Peritonitis -80%, inflammation in the catheter area 3. Concomitant diseases of the abdominal cavity (diaphragmatic, inguinal and umbilical hernia)
    • Continious methods of RRT CVVHDF - extracorporeal blood purification technique due to convective transport of substances through the highly permeable membrane, with the replacement of UF with a special solution 
    • Parametres of CVVHDF The rate of blood flow 4-8 ml/kg/min • Neonates 20-40 ml/min Infants 40-80 ml/min The volume of extraCorporeal circuit 55-72ml Hemofilter membrane area – 0.2 м²
    • Parametres of CVVHDF Substitution rate: 35-50 ml/kg/hr The flow rate of the dialysis solution: equal to or greater than 1.5 times the rate of substitution Heparinization: •Bolus - 20-30 U/kg •Continuous infusion 10-30 U/kg/hr
    • Vascular access Two way catheter under 6 kg - 6,5 Fr from 6 to 15 kg - 8 Fr more than 15 kg - 11 Fr The implantation method  puncture  venesection
    • The puncture site Subcutaneous vein Jugular vein Femoral vein
    • Dynamics of blood creatinine in patients with AKI using PD, HD and CVVHDF C r e a t i n i n 600 HD ГД 550 ПД PD 500 ПВВГДФ CVVGDF 450 400 350 300 250 200 150 100 0 mkmol/l 1 2 3 4 5 6 Сутки dialysis The day of диализа 7 8 9
    • Urea, mmol/l Dynamics of blood urea in patients with AKIusing PD, HD and CVVHDF The day of dialysis CVVHDF PD HD
    • Advantages of CVVHDF        provides continuous purification and UF; better control of azotemia does not require a large flow of blood little effect on hemodynamics can be used in critically ill patients with heart failure, severe edema, cerebral edema; UF rate can be calculated, assigned and adjusted according to the hourly needs of the patient; does not require water treatment and specially trained staff
    • Disadvantages of CVVHDF  Heparinization necessity  Central venous catheterization  Fairly sophisticated equipment  High cost of the procedure  The procedure is conducted by nondialysis staff who has many other responsibilities
    • Factors affecting the type of the dialysis selection  age and anthropometric data  hemodynamic  the presence of respiratory failure  degree of safety consciousness and the presence of seizures  the primary purpose of correction by the RRT  the severity of fluid overload  the severity of azotemia and electrolyte imbalance
    • The algorithm of RRT method selection in children with AKI AKI HD PD Fluid overload Neurological symptoms Hypotension Hypertension CVVGDF CVVGDF Age
    • Starting type of a dialysis in treatment of children with AKI 1991-2004  HD 2006-09 48.5% 15%  PD 51.5% 25%  CVVGDF 60% 2010-12 0,9% 19,6% 79,5%
    • The cost of consumables per 1 day of AKI treatment (USD) Acute PD in child Acute PD in adult Acute HD CVVGDF
    • CONCLUSIONS  CRRT – a choice method at patients with sepsis, the overhydratation, the expressed metabolic and electrolytic violations.  PD – a choice method at stable patients with AKI, at a hemorrhagic syndrome, impossibility of ensuring vascular access, and also basic therapy at long AKI  HD – a choice method at children of advanced age.