aki for general practice

Acute kidney injury

Kasemsan A. MD

Epidemiology 5-7% of hospitalized patientsUp to 30% of patients in ICU

Harrison’s principle of Internal medicine 19 th ed.,2015

Volume depletion Adverse effects of

medications Obstruction of the urinary

tract

Common causes of community-acquired AKI

Sepsis Major surgical procedures Critical illness :heart or liver

failure CI-AKI Nephrotoxic medication

Common causes of hospital-acquired AKI

DefinitionIncreased in SCr by ≥ 0.3 mg/dl (≥ 26.5 µmol/l) within 48 hour

Increased in SCr to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days

Urine volume < 0.5 ml/kg/h for 6 hours.

KDIGO AKI,2012

Staging of AKI

KDIGO AKI,2012

Comparison of RIFLE and AKIN criteria for diagnosis and classification of AKI

KDIGO AKI,2012

Non-oliguric and oliguric AKIOliguria

urine output < 400 ml/dayNon-oliguria

urine output > 400 ml / dayAnuria

urine output < 100 ml/day

Conceptual model of AKI

KDIGO AKI,2012

Novel biomarker for AKINGAL (Neutrophil Gelatinase- Associated Lipocalin)

KIM-1IL-18Cystatin CL – type fatty acid binding protein (L-FABP)

KDIGO AKI,2012

KDIGO AKI,2012

Kashani K. Crit Care. 2013;6;17(1):R25.

IGFBP7 (insulin-like growth factor-binding protein 7)

TIMP-2 (tissue inhibitor of metalloproteinase-2)Diagnosis : [TIMP-2] ・ [IGFBP7] > 0.3 (ng/ml)(2)/1,000

predicts moderate to severe AKI (stage 2-3) within 12 h

AKI : Urinary Biomarkers

Kashani K. Crit Care. 2013;6;17(1):R25.Bihorac A. Am J Respir Crit Care Med. 2014;189(8):932-

9.

Etiology & Pathophysiology


Comprehensive clinical nephrology 5th edition

Pathophysiology of prerenal azotemia

Intravascular volume depletion

Reduced cardiac output

Systemic vasodilation

Renal vasoconstriction

Increased IAP

Renal blood flow = 20% of CO

Tubulo Glomerular Feedback [TGF]

Decreased perfusion pressure

NSAID EffectRAAS Blockade effect

J G A buelo : NEJM 357:797-805 ， 2007

Pathophysiology of intrinsic renal azotemia

Glomerular Tubular Interstitium

Vascular


Pathophysiology of acute tubular necrosis


Tubular effects


Phase of ATN

Drugs and the kidney


Pathophysiology of acute interstitial nephritis

Acute declination in renal function

Inflammatory infiltrates and edema within interstitium

Classic triads (only 10%)Maculopapular rashPeripheral eosinophila or

eosinophiluriaArthralgias

CausesDrugs e.g. Penicillins,

cephalosporins, NSAIDs, PPIsInfection e.g. Pyelonephritis,

leptospirosis, HantavirusAutoimmune e.g. Sjogren

syndrome, sarcoidosis, SLEMalignancy e.g. lymphoma,

leukemiaGlomerular diseaseIdiopathic e.g. TINU syndrome

Pathophysiology of postrenal azotemiaIncreased intratubular

pressureOvercome glomerular

filtration pressureDecreased GFR

Upper tract extrinsic causes

Lower tract causes

Upper tract intrinsic causes

Brenner and Rector’s The kidney 9th edition


Postrenal azotemia without obstructive uropathy by ultrasoundEarly obstruction

Intratubular obstructionVolume depletionPre-existing small kidneyTrapped kidney (e.g. retroperitoneal fibrosis)

Diagnostic approachHistory takingPhysical examinationLaboratory investigation

BUN,CreatinineUrinalysisUrine profile (urine electrolyte, urine creatinine, urine osmole)

ImagingKidney biopsy


Increased BUN Dehydration UGIB Steroid use Hypercatabolic state High protein diet Heart failure Outdated tetracycline

Decreased BUN Liver disease Malnutrition Anabolic state

Increased creatinine

Large muscle bulk Rhabdomyolysis Reduced tubular

secretion Trimethoprim Cimetidine Probenecid

Creatine supplement

Decreased creatinine

Small muscle mass Aging Vegetarian Limb amputation

Pseudoazotemia

Prerenal azotemia

vsAcute tubular necrosis

Diagnostic index

Prerenal AKI

ATN

Urine Na (mEq/L) <20 >40FENa (%) <1 >2

Renal failure index

(UNa/(Ucr/Pcr))

<1 >1

Urine sp.gr. >1.018 About 1.010Urine osmolarity (mOsm/kgH2O)

>500 About 300

Ucr/Pcr >40 <20UUN/BUN >8 <3BUN/Cr >20 <10-15

Urine sediment Hyaline casts Muddy brown casts

AKI with FENa < 1%Prerenal

Extra-renal lossHepatorenal syndromeAcute

glomerulonephritisTTP/HUSEarly urinary tract obstruction

Acute tubular necrosisNon-oliguric AKIContrasted induced

nephropathyACEIs/ARBs/NSAIDsAKI in pregnancySepsisExtensive burnRhabdomyolysisHemolysisUric acid nephropathy

AKI with FENa > 2%Classical ATN

IschemicToxic

Acute interstitial nephritis

Acute renal artery occlusion

Late urinary tract obstruction

Prerenal AKIDiuretics useMineralocorticoid

deficiencyCKDAlkalosis

(bicarbonaturia)Renal salt wastingDiabetes mellitus

Harrison’s Internal medicine 19th edition

RBC

RBC cast

Muddy brown cast

WBC

WBC cast

Eosinophiluria

Hyaline cast

Broad waxy cast

Step to approach azotemia

Step 1: Exclude and correct pseudoazotemiaStep 2: Classification AKI, AKI on top CKD, CKD progression

Step 3: Finding postrenal AKI and correctionStep 4: Find and correct intrinsic renal causes of AKIStep 5: Prerenal AKI vs ATNStep 6: Dialysis if indicated

Adapted from KDIGO guidelines 2012

Step approach to AKI

Management of

Acute kidney injury

KDIGO AKI,2012

Management of AKISpecific treatment is not available for the majority of

forms of AKI.Supportive therapy to ameliorate derangements of fluid

and electrolyte homeostasis and prevent uremic complications.

Elimination of nephrotoxic agents (ACE inhibitors, ARBs, NSAIDs, aminoglycoside, amphotericin B)

KDIGO AKI,2012

Management of AKIInitiation of renal replacement therapy when indicated.The ultimate goals of management are to prevent

death, facilitate recovery of kidney function, and minimize the risk of CKD.

KDIGO AKI,2012

Hemodynamic monitoring and support for prevention and management of AKI

In the absence of hemorrhagic shock, KDIGO suggest using isotonic crystalloids rather than colloids (albumin or starches) as initial management for expansion of intravascular volume in patients at risk for AKI or with AKI. (2B)

KDIGO recommend the use of vasopressors in conjunction with fluids in patients with vasomotor shock with or at risk for AKI. (1C)

KDIGO AKI,2012

Hemodynamic monitoring and support for prevention and management of AKI

KDIGO suggest using protocol-based management of hemodynamic and oxygenation parameters to prevent development or worsening of AKI in high-risk patients in the perioperative setting (2C) or in patients with septic shock (2C).

KDIGO AKI,2012

Glycemic control and nutritional support

In critically ill patients, KDIGO suggest insulin therapy targeting plasma glucose 110–149 mg/dl (6.1–8.3 mmol/l). (2C)

KDIGO suggest achieving a total energy intake of 20–30 kcal/kg/d in patients with any stage of AKI. (2C)

KDIGO suggest to avoid restriction of protein intake with the aim of preventing or delaying initiation of RRT. (2D)

KDIGO AKI,2012

KDIGO suggest administering 0.8–1.0 g/kg/d of protein in noncatabolic AKI patients

without need for dialysis (2D)1.0–1.5 g/kg/d in patients with AKI on RRT (2D)Up to a maximum of 1.7 g/kg/d in patients on continuous

renal replacement therapy (CRRT) and in hypercatabolic patients. (2D)

KDIGO suggest providing nutrition preferentially via the enteral route in patients with AKI. (2C)

KDIGO AKI,2012

Glycemic control and nutritional support

Use of diuretic in AKIKDIGO recommend not using diuretics to prevent AKI.

(1B)

Suggest not using diuretics to treat AKI, except in the management of volume overload. (2C)

KDIGO AKI,2012

Vasodilator therapyKDIGO recommend not using low-dose dopamine to

prevent or treat AKI. (1A)

Suggest not using fenoldopam to prevent or treat AKI. (2C)

Suggest not using atrial natriuretic peptide (ANP) to prevent (2C) or treat (2B) AKI.

KDIGO AKI,2012

Growth factor interventionKDIGO recommend not using recombinant human (rh)

IGF-1 to prevent or treat AKI. (1B)

KDIGO AKI,2012

Adenosine receptor antagonistKDIGO suggest that a single dose of theophylline may

be given in neonates with severe perinatal asphyxia who are at high risk of AKI. (2B)

KDIGO AKI,2012

Prevention of aminoglycoside and amphotericin

related AKIKDIGO suggest not using aminoglycosides for the

treatment of infections unless no suitable, less nephrotoxic, therapeutic alternatives are available. (2A)

KDIGO suggest that, in patients with normal kidney function in steady state, aminoglycosides are administered as a single dose daily rather than multiple-dose daily treatment regimens. (2B)

KDIGO AKI,2012

KDIGO recommend monitoring aminoglycoside drug levels when treatment with multiple daily dosing is used for more than 24 hours. (1A)

Suggest monitoring aminoglycoside drug levels when treatment with single-daily dosing is used for more than 48 hours. (2C)

Suggest using topical or local applications of aminoglycosides (e.g., respiratory aerosols, instilled antibiotic beads), rather than i.v. application, when feasible and suitable. (2B)

KDIGO AKI,2012


related AKI

KDIGO suggest using lipid formulations of amphotericin B rather than conventional formulations of amphotericin B. (2A)

In the treatment of systemic mycoses or parasitic infections, KDIGO recommend using azole antifungal agents and/or the echinocandins rather than conventional amphotericin B, if equal therapeutic efficacy can be assumed. (1A)

KDIGO AKI,2012


related AKI

Other method of prevention of AKI in the critically ill

KDIGO suggest that off-pump coronary artery bypass graft surgery not be selected solely for the purpose of reducing perioperative AKI or need for RRT. (2C)

Suggest not using NAC to prevent AKI in critically ill patients with hypotension. (2D)

KDIGO recommend not using oral or i.v. NAC for prevention of postsurgical AKI. (1A)

KDIGO AKI,2012

Contrast induced AKI

Contrast induced AKIDefine and stage AKI after administration of

intravascular contrast media as per Recommendations (Not Graded)

In individuals who develop changes in kidney function after administration of intravascular contrast media, evaluate for CI-AKI as well as for other possible causes of AKI. (Not Graded)

KDIGO AKI,2012

Assess the risk for CI-AKI and, in particular, screen for pre-existing impairment of kidney function in all patients who are considered for a procedure that requires intravascular (i.v. or i.a.) administration of iodinated contrast medium. (Not Graded)

Risk factorsPre-existing CKDDiabetes mellitusAdvanced CHFHigh dose contrast mediaHemodynamic instability

KDIGO AKI,2012


Consider alternative imaging methods in patients at increased risk for CI-AKI. (Not Graded)

KDIGO AKI,2012


Nonpharmacological preventionstrategies of CI-AKI

Use the lowest possible dose of contrast medium in patients at risk for CI-AKI. (Not Graded)

KDIGO recommend using either iso-osmolar or low osmolar iodinated contrast media rather than high- osmolar iodinated contrast media in patients at increased risk of CI-AKI. (1B)

KDIGO AKI,2012

Pharmacological preventionstrategies of CI-AKI

KDIGO recommend i.v. volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions rather than no i.v. volume expansion, in patients at increased risk for CI-AKI. (1A)

Recommend not using oral fluids alone in patients at increased risk of CI-AKI. (1C)

KDIGO AKI,2012

KDIGO suggest using oral NAC together with i.v. isotonic crystalloids in patients at increased risk of CI-AKI. (2D)

Suggest not using theophylline to prevent CI-AKI. (2C)

Recommend not using fenoldopam to prevent CI-AKI. (1B)

Pharmacological preventionstrategies of CI-AKI

KDIGO AKI,2012

Effects of hemodialysis or hemofiltrationKDIGO suggest not using prophylactic intermittent

hemodialysis (IHD) or hemofiltration (HF) for contrast-media removal in patients at increased risk for CI-AKI. (2C)

KDIGO AKI,2012

Indications for acute renal replacement therapyA : metabolic AcidosisE : Electrolyte imbalanceI : Intoxication / Ingestion of toxic substanceO : fluid Overload that is refractory to diureticsU : signs of Uremia

KDIGO AKI,2012

Mode of RRTConventional intermittent hemodialysis (IHD)Sustained low-efficacy dialysis (SLED)Continuous renal replacement therapy (CRRT)Peritoneal dialysis(PD)

KDIGO AKI,2012

Vascular access for renal replacementtherapy in AKI

When choosing a vein for insertion of a dialysis catheter in patients with AKI, consider these preferences (Not Graded):

First choice: right jugular veinSecond choice: femoral veinThird choice: left jugular veinLast choice: subclavian vein

KDIGO AKI,2012

AKI : TREATMENTSpecific Rx : Rx cause of AKISupportive Rx

1. Maintain hemodynamic and oxygenation2. Monitor VS, I/O, BW3. Monitor BUN, Cr, electrolyte,…4. Discontinue all nephrotoxic agents5. Nutrition : prefer enteral route6. Total energy intake 20-30 kcal/kg/day7. Protein intake g/kg/day

Non-catabolic 0.8-1.0RRT 1.0-1.5CRRT, Hypercatabolic up to a max. of 1.7

8. In critically ill patients : insulin therapy targeting PG 110-149 mg/dL

Take home messages

KDIGO AKI,2012Brenner and Rector’s The kidney 9th edition

9. HypoNa : free water restriction < 1 L/day10. Volume overload : salt restriction < 1.0-1.5 g/day, furosemide 200 mg iv bolus or 20 mg/h iv11. Not using diuretics to enhance kidney function recovery or to reduce the duration or frequency of RRT12. Not using low-dose dopamine, fenoldopam, ANP, rh IGF-113. HyperK : K diet restriction, off ACEI & ARB & K-sparing diuretics, medical Rx14. Metabolic acidosis : NaHCO3 if pH < 7.1515. HypoCa : CaCO3 if symptomatic or NaHCO3 to be administered16. HyperP : P diet restriction, P binders17. HyperMg : avoid Mg-containing medications18. Hyperuricemia : usually mild (< 15 mg/dL),if severe add allopurinol, or recombinant uricase19. Check for changes of drug dosing20. RRT when indicated

Take home messages

KDIGO AKI,2012Brenner and Rector’s The kidney 9th edition

aki for general practice

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