aki in sepsis
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Acute Kidney Injury in Sepsis
Ach Syaiful Ludfi
Departement of Internal MedicineAirlangga School of Medicine-dr.Soetomo Teaching
HospitalSurabaya
2014
INTRODUCTIONAcute Kidney Injury (AKI) : the entire spectrum of the syndrome from minor changes in markers of renal function to requirement for Renal Replacement Therapy (RRT)
AKI in Sepsis 19% patients with moderate sepsis, 23% with severe sepsis and 51% with septic shock
(KDIGO, 2012)
(Majumdar, 2010)
Distinguishing between septic and non-septic AKI may have clinical relevance for physicians
Pathophysiology of AKI in sepsis is not known clearly
Prevention and management important(Rajapakse, 2009)
DEFINITION AKIRIFLE criteria (ADQI, 2004) & AKIN criteria (AKIN, 2007)
DEFINITION AKIStaging AKI (KDIGO, 2012)
AKI is defined as any of the following (Not Graded):•Increase in SCr by ≥ 0.3 mg/dl ( ≥ 26.5 lmol/l) within 48 hours; or•Increase in SCr to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or•Urine volume < 0.5 ml/kg/h for 6 hours.
CAUSES OF AKI
(Lattanzio, 2009; Markum, 2006)
CAUSES OF AKI
(Lattanzio, 2009; Markum, 2006)
Prerenal AKI Postrenal AKI Renal AKISecondary to underperfusion•renal or extrarenal losses•Heart failure•Cirrhosis•Sepsis.
Urinary tract obstructions•Stones•tumor
Tubular cell injury•Ischemia and inflammation (sepsis, surgery)•ToxinsInterstitium•Acute interstitial nephritis (AIN)Glomerulus•acute glomerulonephritisVasculature
Definition AKI in Sepsis
The simultaneous presence of :1.Criteria for AKI,2.The consensus criteria for sepsis3.If possible, the absence of other clear and established, non-sepsis-related causes of AKI (e.g., radiocontrast, other nephrotoxins)
(Ricci, 2009).
PATHOGENESIS OF AKI IN SEPSIS1.Renal Hemodynamics2.Renal Apoptosis3.Endothelial Damage4.Tubular Damage
New studyRBF ????
Increase or decrease ??
(Ricci,2009; Rajapakase, 2009)
Renal Hemodynamics PATHOGENESIS OF AKI IN SEPSIS
Renal Hemodynamics
New HypotesisHyperdynamic sepsis
(Rajapakase, 2009;Kockara, 2013)
PATHOGENESIS OF AKI IN SEPSIS
Renal Apoptosis
Wan, 2003; Havasi, 2011
PATHOGENESIS OF AKI IN SEPSIS
Endothelial Damage
sepsis
Activation of coagulation system by endotoxin, tissuefactor release, thrombocyte and fibrin aggregation
Decrease in fibrinolytic activity, endothelial damage
IL-1b, TNF and PAF increase the neutrophil aggregation and toxic substance release
microthrombi
glomerular capillaries
(Havasi, 2011; Kockara, 2013)
PATHOGENESIS OF AKI IN SEPSIS
Tubular Damage
Necrosis or apoptosis
Tubular epithelium lose basal membrane adhesion quality
Excreted to the tubular lumen
Tubular epithelium cylinders or granular cylinders In urine
Microobstruction (Kockara, 2013)
PATHOGENESIS OF AKI IN SEPSIS
EARLY DIAGNOSIS AKIBUN and serum creatinine are not very sensitive or specific affected by many renal and nonrenal factors
New Biomarker• Biological marker of the inflammatory process : Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and IL-18• Tubular protein : kidney injury molecule-1 (KIM-1), Urine sodium/hydrogen exchanger isoform 3 (NHE3) and Liver fatty acid-binding protein (L-FABP)• Biological markers of tubular disease : α1-microglobulin, β2-microglobulin, N-acetyl-β-D-glucosaminidase, etc
Edelstein, 2008; Parikh, 2008; Roesli, 2008
EARLY DIAGNOSIS AKI
Edelstein, 2008; Parikh, 2008; Roesli, 2008
BiomarkerName
SampleSource
CardiopulmonaryBypass (CPB)
ContrastNephropathy
Sepsis orICU Setting
KidneyTransplant (tx)
NGAL Urine 2 hrs post-CPB 4 hrs postcontrast
48 hrs before AKI
12–24 hrs post-tx
IL-18 Urine 4-6 hrs post-CPB Not tested 48 hrs before AKI
12–24 hrs post-tx
KIM-1 Urine 12-24 hrs post-CPB
Not tested Not tested Not tested
NGAL Plasma 2 hrs post-CPB 2 hrs postcontrast
48 hrs before AKI
Not tested
Cystatin C Plasma 12 hrs post-CPB 8 hrs postcontrast
48 hrs before AKI
Variable
AKI EVALUATIONAKI
Clinical evaluation and physical examination.
Clinical Test
Lab values
AKI stageKDIGO, 2012
Stage-based management of AKI
KDIGO, 2012
AKI managementA.Maintain hemodynamic status
a. Status Volume Optimalizationb. Vasopressor usec. Diuretic use
B. Avoid nephrotoxic drugsC. Avoid nephrotoxic contrast mediaD. Glycemic ControlE. NutritionF. Renal Replacement Therapy
A. Maintain hemodynamic status
a. Status Volume Optimalization
Ronco,2008;Majumdar,2010; KDIGO, 2012
b. Vasopressor use
Rajapakse,2009; Majumdar,2010; KDIGO, 2012
A. Maintain hemodynamic status
c. Diuretic use
Bagshaw, 2007; KDIGO, 2012
A. Maintain hemodynamic status
B. Avoid nephrotoxic drugs
KDIGO suggest not using aminoglycosides for the treatment of infections unless no suitable, less nephrotoxic, therapeutic alternatives are available
Perazella MA, 2012; KDIGO, 2012
C. Avoid nephrotoxic contrast mediaAssess the risk for CI-AKI
Consider alternative imaging methods in patientsat increased risk for CI-AKI
If the procedure still needed : use the lowest possible dose of contrast medium and using either iso-osmolar or lowosmolar iodinated contrast media
KDIGO, 2012
D. Glycemic Control
Rajapakse,2009;Majumdar,2010; KDIGO, 2012
E. Nutrition
Ricci, 2011; KDIGO, 2012
E. Nutrition
Ricci, 2011; KDIGO, 2012
F. Renal Replacement Therapy
Two fundamental questions in severe AKI : Whether or not to provide RRT ?When to start RRT ?
Initiate RRT emergently when life-threatening changes in fluid, electrolyte, and acid-base balance exist
KDIGO, 2012; Rajapakse,2009;Majumdar,2010
F. Renal Replacement Therapy
Goals treatment of AKI with RRT :1.To maintain fluid and electrolyte, acid-base, and solute homeostasis.2.To prevent further insults to the kidney3.To permit renal recovery; and 4.To allow other supportive measures (e.g., antibiotics, nutrition support) to proceed without limitation or complication
Intermittent hemodialysis (IHD) or CRRT?1. No difference in mortality2. CRRT may be the preferred mode in very unstable patients
KDIGO, 2012; Rajapakse,2009;Majumdar,2010
CONCLUSION
• AKI in Sepsis, a commonly condition in an ICU• The patophysiology AKI in sepsis not fully understood• A better understanding of AKI in sepsis is required to
implement prevention strategies and appropriate therapy
• Risk factors identification, evaluation and appropriate management are important in septic condition to prevent AKI
THANK YOU
Schematic representation of the inflammatory response to sepsis and resulting kidney injury. (Modified from205; reprinted with permission. Jaber BL et al: Blood Purif 22: 101–111, 2004). Abbreviations are: GFR, glomerular filtration rate; NAG, N-acetyl- -D-glucosaminidase; KIM, kidney injury molecule 1.
dopamin• At low doses (0.5-3.0 μg/kg/min), dopamine acts predominantly on D1
receptors in the renal, mesenteric, cerebral and coronary beds resulting in selective vasodilation. Some reports suggest that dopamine increases urine output by augmenting renal blood flow and glomerular filtration rate and natriuresis by inhibiting aldosterone and renal tubular transport [2]. But the clinical significance of “renal-dose” dopamine is somewhat controversial because a renal protective effect has not been demonstrated.
• At intermediate doses (3-10 μg/kg/min), dopamine also stimulates β1 receptor and increases cardiac output (CO), predominantly by increasing stroke volume with variable effect on heart rate.
• At higher dose (10-20 μg/kg/min), the predominant effect of dopamine is to stimulate α1-adrenergic receptors and produce vasoconstriction with an increased systemic vascular resistance (SVR), and the sum of these effects is an increase in mean arterial pressure (MAP)
NE• Noradrenaline (also known as norepinephrine) is a potent α1-adrenergic
receptor agonist with modest β-agonist activity because of which it is incorrectly labelled as a pure vasopressor
• However, it has shown effects on contractility in critical illness [9].• It primarily increases systolic, diastolic and pulse pressure and has a
minimal net impact on CO. It has minimal chronotropic effects because of which it is a drug of choice in settings where heart rate stimulation is undesirable. Coronary flow is maintained to certain extent because of its vasoconstrictor effects [10]. Due to relative scarcity of cerebral vascular adrenergic receptor, high doses of noradrenaline can be safely used to maintain cerebral perfusion pressure without significantly compromising the circulatory flow
• Dopamine increases MAP and cardiac output, primarily due to an increase in stroke volume and heart rate.
• Norepinephrine increases MAP due to its vasoconstrictive effects, with little change in heart rate and less increase in stroke volume compared with dopamine.
• Norepinephrine is more potent than dopamine and may be more effective at reversing hypotension in patients with septic shock.
• Dopamine may be particularly useful in patients with compromised systolic function but causes more tachycardia and may be more arrhythmogenic than norepinephrine
AIN• The mechanism of drug-induced AIN is unknown, but an
immunological basis is suspected. Drugs can elicit an immune response leading to AIN in different ways. The drug can bind to a normal component of the tubular basement membrane (TBM) and act as a hapten or the drug can mimic an antigen normally present within the TBM or the interstitium and induce an immune response that will also be directed against this antigen. Other ways to evoke an immune response include the drug binding to the TBM or deposit within the interstitium and act as a planted (trapped) antigen. The drug can also elicit the production of antibodies and become deposited in the interstitium as circulating immune complexes
• HAART include crystal-induced obstruction secondary to use of protease inhibitors (mainly indinavir and atazanavir), and proximal tubule damage related to the nucleotide analog reverse transcriptase inhibitor tenofovir. Acute kidney injury (AKI) can occur following tenofovir-induced tubule dysfunction or as a result of severe mitochondrial dysfunction and lactic acidosis induced by nucleoside reverse transcriptase inhibitors