AKI in Sepsis

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


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)


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)


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


c. Diuretic use

Bagshaw, 2007; KDIGO, 2012


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

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AKI in Sepsis