Approach to Acute Kidney Injury

Anna Jin, M.D.

LBVA/UCI7/21/2014

Learning Objectives

Definitions and classification of AKI

Epidemiology and clinical outcome

Diagnosis and etiology

Approach and management of AKI

Risk factors and preventive strategies

Definition of AKI

a sudden, sustained, and usually reversible decrease in the glomerular filtration rate (GFR) occurring over a period of hours to days.

> 30 definitions used in published studies

KDIGO Definition of AKI ( 2012 )

Defined by any of the following:

Increase in SCr by ≥0.3 mg/dL within 48 hours

Increase in Scr by ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days

Urine volume <0.5 mL/kg/h for six hours

KDIGO Classification of AKI ( 2012 )

Stage Serum creatinine Urine output

1 1.5-1.9× baselineOR>0.3 mg/dL

<0.5 ml/kg/hr for 6-12 hrs

2 2-2.9× baseline<0.5 ml/kg/hr > 12 hrs

3 3 times baselineORincrease in Cr to ≥4.0 mg/dLOR Initiation of RRT

<0.3 ml/kg/hr > 24 hrsORAnuria > 12 hrs

KDIGO Clinical Practice Guideline for AKI. Kidney Int 2012

Definitions of Terminology

Azotemia - the accumulation of nitrogenous wastes (high BUN)

Uremia – clinical manifestation (symptomatic renal failure)

Oliguria – UOP < 400-500 mL/24 hours

Anuria – UOP < 100 mL/24 hours

Epidemiology

≈ 5-10% in hospitalized pts

≈ 70% in critically ill pts

5-6% ICU pts require RRT

Once AKI occurred, the treatment is supportive, at an annual cost $10 billion in the US.

Incidence of Non-Dialysis AKI

Kidney Int 2007

Incidence of Dialysis-Requiring AKI

Kidney Int 2007

In-Hospital Mortality Rate 1992-2001

33% - AKI requiring dialysis

27.5% - AKI not requiring dialysis

4.6% - no AKI

JASN 17:1135-1142, 2006

Chertow et al, JASN 16:3365-70; 2005

AKI and Mortality

Brigham and Womens, 9210 adults Multivariable Odds Ratio for Death

•AKI (Δ in SCr >0.5)

•Age (per 10 yr)•CKD•CV dis.•Respiratory dis•GI dis.•Cancer•Infection

6.5

1.7

2.5

1.5

3

2.4

2.9

7.5

<0.0001

<0.0001

<0.0001

<0.04

<0.0001

<0.001

<0.0001

<0.0001

Increase in Serum Creatinine from Baseline

Chertow GM et al. J Am Soc Nephrol 2005;16:3365

90 Day Mortality Rate in 2001

44.8% - AKI requiring dialysis

40.3% - AKI not requiring dialysis

12.1% - no AKI

JASN 17:1135-1142, 2006

Lai CF et al. Crit Care 2012

N=634

Ishani A et al. J Am Soc Nephrol 2009

N= 233.803

Acute kidney injury increases risk of ESRD among elderly

Hou SH, Bushinsky DA, Wish JB. Am J Med 1983; 74: 243-8.Nash K, Hafeez A, Hou S. Am J Kidney Dis. 2002; 39: 930-6.

Kaufman J, Dhakal M, Patel B, Et al. Am J Kidney Dis 1991; 17: 191-8.

Etiology of AKI

0

10

20

30

40

50

60

70

80

Prerenal Intrarenal Obstruct Idiopath

Outpatient

Inpatient

ATN is the cause in more than 90%. Sepsis is the leading

cause of ATN

To function properly kidneys require:

Normal renal blood flow Prerenal d/t renal hypoperfusion

Functioning glomeruli and tubules Renal (Intrinsic)

Clear urinary outflow tract for drainage and elimination of formed urine Post renal obstruction

AcuteTubularNecrosis

AcuteInterstitialNephritis

AcuteGN

AcuteVascularSyndromes

IntratubularObstruction

Classification of the Etiologies of AKI

PrerenalAKI

PostrenalAKI

IntrinsicAKI

AcuteRenalInjury

Prerenal AKI

Intravascular volume depletion:

-bleeding, GI loss, Renal loss, Skin loss (burn), Third space loss, poor oral intake (NPO, AMS, anorexia)

Decreased effective circulating volume:-congestive heart failure, cirrhosis, nephrotic syndrome, sepsis

Decreased flow through renal artery:-RAS or occlusion (compartment syndrome), hepatorenal syndrome, hypercalcemia

-pharmacologic impairment (RAAS blocker, NSAIDs, CNI)

Prerenal Azotemia Tx In early stages can be rapidly corrected by

aggressive normalization of effective arterial volume.

Correction of volume deficits

Optimization of cardiac function

Discontinuation of antagonizing medications

NSAIDs/COX-2 inhibitors

Diuretics

RAAS blockers

Renal / Intrinsic AKI

Tubule: ATN (sepsis, ischemic, toxins)

Interstitium: AIN (Drug, infection, neoplasm)

Glomerulus: AGN (primary, post-infectious,

rheumatologic, vasculitis, HUS/TTP)

Vasculature: Atheroembolic dz, renal artery thromboembolism, renal

artery dissection, renal vein thrombosis

Intratubular Obstruction myoglobin, hemoglobin, myeloma light chains,

uric acid, tumor lysis, drugs (bactrim, indinavir,

acyclovir, foscarnet, oxalate in ethylene glycol toxicity)

Acute Tubular Necrosis (ATN)

Sepsis (48%)

Ischemia (32%) prolonged prerenal

azotemia Hypotension hypovolemic shock cardiopulmonary arrest cardiopulmonary bypass

Direct toxic Injury (20%)

Exogenous Radiocontrast Aminoglycosides Vancomycin Amphotericin B Cisplatin Acyclovir Calcineurin inhibitors HIV meds (tenofovir)

Endogenous (pigment nephropathy) Rhabdomyolysis Hemolysis

Laboratory Findings in Acute Kidney Injury Index Prerenal

Azotemia Oliguric AKI (ATN)

BUN/PCr Ratio >20:1 10-15:1

Urine sodium (UNa), meq/L

<20 >40

Urine osmolality, mosmol/L H2O

>500 <400

-Fractional excretion of sodium

-FEUrea

<1% <35%

>2%

>35%

Response to volume Cr improves with IVF Cr won’t improve much

Urinary Sediment Bland, Hyaline Muddy brown granular casts, cellular debris, tubular epithelial cells

Pitfalls: Fractional Excretion of NaPitfalls: Fractional Excretion of Na

Pre-existing CKD: FeNa 2-3 even without tubular injury

Poor sensitivity with diuretics use Picture might be muddied by fluid therapy

Etiologies of FeNa < 1% hepatorenal syndrome contrast nephropathy rhabdomyolysis acute glomerulonephritis early obstructive uropathy

Postrenal AKI: Classification

Level of obstruction

Upper tract (ureters)

Lower tract (bladder outlet or urethra)

Degree of obstruction

Partial vs. Complete

Type

Anatomic lesion (unilateral vs. bilateral)

Functional

Duration (Acute vs Chronic)

Cause (Congenital vs Acquired)

Etiologies: Upper tract obstruction

Intrinsic:NephrolithiasisBlood clotPapillary

necrosisCancer

Extrinsic:

Retroperitoneal or pelvic malignancy

Endometriosis/Prolapsed uterus

Abdominal aortic aneurysm or Iliac artery aneurysm

Retroperitoneal fibrosis

Etiologies: Lower tract obstruction

BPH or prostate cancer Bladder cancer Urethral strictures Bladder stones Blood clots Functional obstruction as a result of

neurogenic bladder

Postrenal AKI tx Prompt recognition and relief of obstruction can

prevent the development of permanent structural damage.

Lower tract obstruction (bladder catheter)

Upper tract obstruction

ureteral stents

percutaneous nephrostomies

Monitor for post-obstructive diuresis

Recovery of renal function dependent upon duration of obstruction.

How do we assess a pt with AKI?

Is this acute or chronic renal failure?

Establish baseline Cr and assess Cr trend

History and examination

Small kidneys on ultrasound (except for in -Diabetes, PCKD, Urinary Tract Obstruction)

Hilton et al, BMJ 2006;333;786-790

AKI: Focused History

Prenal hx: N/V/D? Oral intake? Diuretics? Hx of heart dz, liver dz, previous renal dz?

Post-renal sxs: hesitancy, frequency, urgency, weak stream, dribbling, feeling of incomplete bladder emptying, flank pain. h/o kidney stones or BPH? Spinal cord injury? Anticholingergic meds?

Any recent illnesses? Fever? Rashes?

Any recent surgery?

Cardiovascular instability?

Toxin exposure: new medications (Abx, NSAIDs)? IV contrast?

Change in urination, any edema/SOB/Wt. gain?

Look for temporal link of exposure or risk factor to elevation of Cr or decline in UOP

How to assess volume? History (intake, fluid loss, meds)

Postural blood pressure and pulse

Daily weights

In’s/Out’s, fluid balance/fluid challenge

Signs of volume depletion:

-Dry mouth, Increased thirst, Lightheadedness, Muscle cramps, extremities are cool to the touch, palpitations, reduced and dark urine, syncope

-PE: Listlessness/AMS/LOC, tachycardic, weak rapid pulse, hypotensive (orthostatic vitals), tachypnic, increased Temp, poor capillary refill, decreased skin turgor, flattened neck veins, little or no urination for several hrs

U/A, Urine protein/Cr, Urine Eosinophilla

FeNa, FeUrea

CPK, uric acid

Urine microscopy:

Muddy brown casts in ATN

WBC casts in AIN

RBC casts in AGN

Post-void residual (>100-150 ml c/w voiding dysfunction)

bladder catheterization

renal ultrasound

Management of AKI: general principle

No therapy to date have shown efficacy in treating AKI.

Identify the etiology and treat the underlying cause

Optimization of hemodynamics to increase renal perfusion

Lack of benefit – low dose dopamine, loop diuretics only if markedly fluid overload

Identify and aggressively treat infection (early removal of foley catheters, and minimize indwelling lines)

Management of AKI: treat complications

Correct fluid imbalances: strict I/O’s, daily wts. determine fluid balance goals daily, fluid selection or diuresis, readjust for UOP recovery, post diuresis or dialysis

Electrolyte imbalances (low K/phos diet, binder)

Metabolic acidosis (Bicarb deficit, mode and rate of replacement)

Nutrition: adjust TPN/protein intake

Medication dosing: adjustment for eGFR to avoid under or over dosing, timing for dialytic therapy, reassess dosing for renal recovery or dialysis modality)

Procedural considerations (prefer non-contrast CT, appropriate to delay contrast exposure, prophylaxis)

Nephrotoxic Drug Exposure

Minimizing nephrotoxinAvoid Aminoglycosides, Amphotericin,

Bactrim, Vancomycin, NSAIDs, IV contrast, Fleet’s enemas

Renal dose medications – especially antibiotics and monitor level

Cautious use (metformin, long acting oral hypoglycemic agents, insulin, gemfibrozil and statins, neurotin, colchicine/allopurinol, morphine/codeine, lmwh)

Ancient Chinese Medical Text

The inferior doctor treats actual illness.

The mediocre doctor attends to impending illness.

The superior doctor prevents illness.

2600 BC - Huang Dee Nai-Chang

Be aware of pts who are at risk for AKI

Volume depletion or Hypotension

Sepsis

Pre-existing renal, hepatic, or cardiac dz

Diabetes mellitus

Elderly

Exposure to nephrotoxins

Aminoglycosides, amphotericin, immunosuppressive agents, chemo., NSAIDs,, RAAS blockers, intravenous contrast media

Post cardiac or vascular Surgery pts or ICU pts with multiorgan failure

Take Home Messages: AKI

AKI is increasingly common. It involves high cost of management, carries a high morbidity

and mortality risks.

The most common cause of in-hospital AKI is ATN that results from multiple acute insults (sepsis, ischemia, or nephrotoxin).

No drug treatment has been shown to limit the progression of, or speed up recovery from AKI.

Review medications and adjust dose

Recognize risk factors

The Best Treatment is PREVENTION and avoid further renal damage!!!

Examine pt: BP? Dry? Septic (vasodilated)?

Flush foley (sediment can obstruct outflow)

Check I/Os (has he been drinking?)

Give IV BOLUS (250-500cc IVF), see if pt pees in next 30-60 min

If he pees, then he was dry

If he doesn’t pee, then he’s either REALLY dry or in renal failure

Check UA, UCx, urine lytes

Consider Renal U/S if reasonable

THANK YOU!

RIFLE Criteria for AKI (2005)

Definition of AKI based on AKIN“Acute Kidney Injury Network” ( 2007 )

Stage Increase in Serum Creatinine

Urine Output

1 1.5-2 times baseline OR 0.3 mg/dl increase from baseline

<0.5 ml/kg/h for >6 h

2 2-3 times baseline <0.5 ml/kg/h for >12 h

3 3 times baseline OR0.5 mg/dl increase if baseline>4mg/dlORAny RRT given

<0.3 ml/kg/h for >24 hOR Anuria for >12 h

RIFLE2004

AKIN2007

LIMITATIONS STRENGTHS

KDIGO2012