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Acute kidney injury - PPT Presentation

DrshahramsajjadiehMD nephrologist IDENTIFICATION Azotemia Uremia or Uremic syndrome ARF hours to days RPRFdays to weeks CRF months to years ID: 809605

arf renal aki acute renal arf acute aki atn failure urine casts injury volume patients disease tubular prevention oliguric

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Slide1

Slide2

Acute kidney injury

Dr.shahram.sajjadieh.MD nephrologist

Slide3

IDENTIFICATION

Azotemia

Uremia or Uremic syndrome ARF (hours to days) RPRF(days to weeks) CRF (months to years)

Slide4

ARF

Acute

kidney injury (AKI) or Acute renal failure (ARF)

Abrupt decrease of renal function sufficient to result in:

Retention of nitrogenous waste products

loss of regulation of extracellular volume and electrolytes

Rapid deterioration of renal function

(increase of serum

cr of >0.3-0.5 mg/dl in <48-72hrs or a percentage increase of >50%)Decreased urine output(<0.5 ml/kg/hr for >6hr) (usually but not always) Oliguria: <400 ml urine output in 24 hours Anuria: <100 ml urine output in 24 hours

Slide5

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

Stage

Increase in Serum CreatinineUrine Output11.5-2 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

OR

0.5 mg/dl increase if baseline>4mg/dlORAny RRT given <0.3 ml/kg/h for >24 hOR Anuria for >12 hMehta R, Kellum J, Shah S, et al.: Acute kidney Injury Network: Report of an Initiative to improve outcomes in Acute Kidney Injury. Critical Care 2007; 11: R31.

Slide6

RIFLE

classificationARFIndicator Classes

R

isk

of renal injury

I

njury

to the kidney

Failure of kidney function

Outcome Classes

Loss

of kidney function

E

nd-stage Kidney Disease

Slide7

RIFLE classification

GFR/Cr criteria

Urine Output criteria

R

isk

Increase in

cr

x1.5

Or GFR decrease >25%

UO < 0.5ml/kg/hr for 6hrs

I

njury

Increase in

cr

x 2

Or GFR decrease >50%

UO < 0.5ml/kg/hr for 12hrs

F

ailure

Increase in

cr

x 3

Or GFR decrease >75%

UO < 0.3ml/kg/hr for 24 hrs or

Anuria

for 12hrs

L

oss

Persistent ARF = complete loss of renal function > 4 weeks

E

SRD

End Stage Renal Disease > 3 months

Slide8

ARF

8

Median hospital length of stay stratified by single acute organ system dysfunction, including ARF

Slide9

Mortality

Dialysis requiring = 40-90%

Increased mortality even in patients not requiring dialysis25% increase in creatinine associated with a mortality rate of 31% compared with 8% for matched patients without renal failure

Slide10

Non-Oliguric vs. Oliguric vs. Anuric

Oliguric renal failure.

Functionally, urine output less than that required to maintain solute balance (can’t excrete all solute taken in).Defined as urine output < 400ml/24hr.Anuric renal failure.Defined as urine output < 100ml/24hr.Less common – suggests complete obstruction, major vascular catastrophy, or more commonly severe ATN.

Slide11

Non-Oliguric vs. Oliguric vs. Anuric

Classifying by urine output may help establish a cause.

Oliguria – more common with obstruction, prerenal azotemiaNonoliguric – intrarenal causes – nephrotoxic ATN, acute GN, AIN.More importantly, assists in prognosis.Significantly higher mortality with oliguric renal failure.80% vs. 25% mortality in Oliguric vs. non-oliguric ARFNonoliguric renal failure may also suggest greater liklihood of recovery of function.

Slide12

ARF

12

Etiology of ARF

Slide13

ARF

Prerenal

Azotemia 55% Renal 40%

ATN

90%

(Ischemic ,

nephrotoxic

)

AIN

AGN or

Vasculitis

Acute Renovascular DiseaseMicrovascular (HUS_TTP, atheroemboli)Post renal 5% Admission in wards ~ 5% Admission in ICU ~ 30%

Slide14

Useful Features That Suggest CRF or ARF

Chronic Hx of:

Nocturia, polyuria, edema or hematuriaPruritus, neuropathy, impotence, other uremic symptomsUnderlying predisposing illness (DM, HTN)

Slide15

Useful Features That Suggest CRF or ARF (cont.)

Objective Findings:

Bilateral Small KidneysRenal OsteoDystrophyBand keratopathyCarbamylated Hemoglobine

Slide16

Useful Features That Suggest CRF or ARF (cont.)

Less reliable:

AnemiaHypocalcemiaHyperphosphatemia

Slide17

Differentiation between ARF and CRF

Acute

Chronic

History

Short

(days-weeks)

Long (

month-years)

Hb concentration

Normal

Low

Renal size

Normal

Reduced

ROD

Absent

Present

Peripheral neuropathy

Absent

Present

Serum Cr

Acute reversible increase

Chronic irreversible

Slide18

Epidemiology

Prevalence

1-5% all patients admitted to hospital10-30% patients admitted to ICUEtiologyHemodynamic 30%Parenchymal 65%Acute tubular necrosis 55%Acute glomerulonephritis 5%Vasculopathy

3%

Acute interstitial nephritis 2%

Obstruction 5%

Slide19

Clinical Approach to Acute Renal Failure

Slide20

AKI: Diagnostic studies-urine

Urinalysis for sediment, casts

Response to volume repletion with return to baseline SCr 24-72 hr c/w prerenal eventUrine Na; FENa FENa (%) = UNa x SCr x 100 SNa x UCrFENa < 1%: PrerenalFENa 1-2%: MixedFENa > 2%: ATNHansel’s stain

Slide21

BUN/Creatinine ratio.

> 20:1 – suggest prerenal or obstruction.

Can be elevated by anything leading to increased urea production/absorption.GI bleedTPNSteroidsDrugs – Tetracycline.Creatinine in anephric state typically only rises 1mg/dl/day.If greater – should be concerned for rhabdomyolysis

Slide22

ATN vs. Prerenal Azotemia

Indices Prerenal ATN UNa < 20 > 40 FeNa < 1% > 1% U/PCreat > 40 < 20

Slide23

Confounding Variables in the Diagnosis of Pre-renal Azotemia versus ATN

A low urine Na can also be seen in:

Contrast induced ATNEarly ATN or obstructionAcute Glomerulonephritis and Nephrotic Syndrome Diuretics can elevate the urine Na Jaundice may induce “muddy brown” cast formation

Slide24

Urinalysis in Acute Kidney Injury

Prerenal

PostrenalAKIGlomerulopathy

Vasculitis

Thrombotic

MA

Pyelonephritis

Interstitial nephritis

AIN

Athero

-

embolic AKIATNMyoglobinHemoglobinUric acidToxinsDrugsPlasma cell dyscrasiaHematuriaRBC castsproteinuriaWBCWBC castsEosinophils

RTE cells

Pigmented

casts

Crystalluria

Non-

albumin

proteinuria

Abnormal sediment

Normal/bland

Slide25

Urinary Sediment Findings in

Intra-Renal Acute Renal Failure

Intra-renal Acute Renal Failure

Dysmorphic Hematuria

Red cell casts

Oval fat bodies

Fatty Casts

Muddy brown casts

Renal tubular epithelial

cells and casts

White cells

White cell casts

Eosinophiluria

Glomerulonephritis

Atheroembolic disease

Thrombotic

microangiopathy

Minimal change disease

Focal segmental

glomerulosclerosis

Albuminuria

Tubular proteinuria

Tubular epithelial

injury

-Ischemic

Nephrotoxic

Interstitial nephritis

Urinary tract

infection

Crystalluria

Drug toxicity

Urate crystals

-Urate nephropathy

Calcium oxalate crystals

-ethylene glycol

Slide26

ARF

Clinical feature of ARF

Symptoms and/or signs of RF:Weakness and easy fatiguability (from anemia), Anorexia Vomiting

Mental status changes or Seizures

Edema,…

Systemic symptoms and findings:

Fever, arthralgias, pulmonary lesions

Slide27

ATAPOUR

Slide28

Acute Kidney Injury

Prerenal

Azotemia: - fall in GFR secondary to renal hypoperfusion that potentially has rapid reversible component with restoration of effective intravascular volume or perfusion pressure.

Slide29

Syndromes of Renal Hypoperfusion

Pre renal A.

ACN

ATN

Intermediate syndrome

Slide30

Syndromes of Renal

Hypoperfusion

Postulated Major Pathologic Mechanism

Syndrome

GFR

(ml/min

)

Preventability

Cortical

hypoperfusion

Prerenal

Azotemia

40-100

Immediate

Medullary

hypoperfusion

Intermediate syndrome

20 - 60

Within 1

3 days

Medullary ischemia

ATN

0 - 25

Within 1

3 weeks

Cortical ischemia

ACN

0 - 5

Unpredictable

Slide31

ARF

Pre-renal AKI

Volume depletion Renal losses (diuretics, polyuria

)

GI losses (vomiting, diarrhea)

Cutaneous losses (burns,…)

Hemorrhage

Decreased cardiac output

 

HF

Pulmonary embolus

Acute MI Severe valvular heart disease Abdominal compartment syndrome (tense ascites)

Slide32

Conditions that Lead to Pre-renal Acute Renal Failure

Generalized

or Localized Reduction in Renal Blood Flow

Ischemic

Acute Renal Failure

Intravascular Volume Depletion

Decreased Effective Circulating Volume

CHF Cirrhosis Nephrosis

Medications

CsA, Tacrolimus

ACE inhibitors NSAIDSRadiocontrast Amphotericin BAminoglycosidesHepatorenalSyndrome

Sepsis

Large-vessel Renal Vascular Disease

Renal Artery Thrombosis

Renal Artery Embolism

Renal Artery Stenosis or Crossclamping

Small-vessel Renal Vascular Disease

Vasculitis Atheroemboli

Thrombotic Microangiopathies

Transplant Rejection

Slide33

Slide34

ARF

Acute

Tubular Necrosis(ATN)Most common cause of intrinsic cause of ARFOften multifactorial

Ischemic ATN:

Hypotension, sepsis, prolonged pre-renal state

Nephrotoxic

ATN:

Contrast, Antibiotics, Pigments,

heme

protein,…

Slide35

Course of Ischemic ATN

Prerenal Azotemia

ATNInitiationExtensionMaintenanceRecoveryARF

Slide36

Phases of Ischemic Epithelial Tubular Injury

Time

GFR

Pre-renal

Initiation

Extension

Maintenance

Recovery

Slide37

ATN -

Pathophysiology

Initiation (hours to days) GFR due to: Renal blood flowObstruction of tubules by castsBack leak of filterate

ARF

Slide38

ATN -

Pathophysiology

2. Extension:Continued ischemic injury & inflammation Cellular apoptosis/necrosis /sloughing Disruption of normal epithelial integrity

Abnormal tubular function

Luminal obstruction

Capillary sloughing and worsening ischemia

ARF

Slide39

ATN - Pathophysiology

3.

Maintenance (1-2 weeks)Release of vasoactive mediators from injured endothelial cellsCongestion of medullary blood vesselsReperfusion injury induced by reactive oxygen species & inflammatory mediators release by leukocytes & parenchymal cellsTubuloglomerular feedback

ARF

Slide40

ATN -

Pathophysiology

4. RecoveryTubular epithelial cell repair and regeneration gradual return of GFR toward premorbid levelsARF

Slide41

Slide42

Urine Indices Used in the

D.Dx

of Prerenal & Intrinsic Azotemia

Diagnostic Index

Prerenal

Azotemia

Intrinsic

Azotemia

Urine SG

>1.018

<1.012

Urine Osmolality

> 500

< 250

BUN / Cr

>20

<10 - 15

Urinary Na conc

.(mEq/l)

<10

>20

Fractional Excretion of Na(%)

UNa×Pcr×100 / PNa×Ucr

<1

>1

Urine sediment

Hyaline casts

Muddy brown granular casts

Slide43

ATN and Mortality

Rising RIFLE class associated with increasing mortality

Patients who are treated with RRT still have a mortality of 50-60%ARF

Slide44

Risk Factors for Ischemic Tubular Injury

Volume depletion

AminoglycosidesRadiocontrastNSAIDs, Cox-2 inhibitorsSepsisRhabdomyolysisPreexisting renal diseaseHTNDiabetes mellitusAge > 50

Cirrhosis

Slide45

ARF

Slide46

ARF

Post-renal AKI

Ureteric obstruction Stone, Clot,… Ligation during pelvic surgery

Bladder neck obstruction

BPH

Neurogenic bladder

Drugs (TCA, ganglion blockers)

Stone disease, hemorrhage/clot

Urethral obstruction

Strictures, Clot,…

Slide47

Slide48

Sepsis and AKI

Sepsis accounts for nearly 50% of all causes of AKI

Combination of FactorsImmunologicalToxicInflammatoryEffect renal microvasculature and Tubular cellsARF

Slide49

Tubulointerstitial Nephropathy

Definition

: A group of clinical disorders that affect principally the renal tubules and interstitium with relative sparing of glomeruli and renal vasculature

Classification:

AIN

CIN

Slide50

Acute Interstitial Nephritis

AIN is a clinicopathologic syndrome of:

ARFAssociated with interstitial edema and cellular infiltrateEtiologyIdiopathic Secondary

Slide51

Acute Interstitial Nephritis

10-20% of pts with ARF who have had a renal biopsy have AIN

Slide52

Acute Interstitial Nephritis

Etiology

( Secondary):DrugsAntibiotics, NSAIDs, Allopurinol, Diuretics,…Systemic infections

Legionnaires disease,

Leptospirosis

, Strep, CMV,…

Primary Renal Infections

Acute bacterial

pyelonephritis

Reflux nephropathy

Immune disorders

SLE, Sjogrens syndrome,…

Slide53

Acute Interstitial Nephritis-Etiology

Allergic/Drug induced

AutoimmuneSarcoid ,SLE ,Sjogren’s ToxinsChinese herb nephropathy Heavy metalsLight chain cast nephropathyInfiltrativeLeukemia ,LymphomaInfections (Legionella, CMV, HIV, Toxoplasma)

Slide54

Acute Interstitial Nephritis

Clinical Presentation

Non-oliguric ARFFever in allergic and infectious types (except NSAID type)Rash in allergic type (except NSAID induced)EosinophiliaUA: WBC casts Eosinophiluria (allergic) Lumphocyturia (NSAID related)

Slide55

Acute Kidney Injury: AIN causes

DRUGS

ACEIAllopurinolCephalosporinsCimetidineFluoroquinolonesLoop diueticsNSAIDSPCNPhenytoinRifampinSulfonamidesTegretolThiazidesINFECTIONBacterialAgents causing pyelonephritisLegionella

Brucella

Yersinia

Viral

Hantavirus

HIV

CMV,EBV,HSV

Slide56

Pathophysiology

– drug induced AINDrug-induced AIN is secondary to immune reactionAIN occurs only in a small percentage of individuals taking the drugAIN is not dose-dependentAssociation with extrarenal manifestations of hypersensitivityRecurrencence after re-exposure

Slide57

NSAID versus Beta-lactam AIN

Beta-lactam NSAIDDuration of exposure 2 weeks 5 monthsFever/rash/eosinophilia 80% 20%Eosinophiluria 80% 15%> 3 gm proteinuria < 1% 83%Rate of recovery Fast Slow

Chronic renal failure Rare Common

Benefit of steroids Probably Probably not

Slide58

Laboratory Findings in AIN

Acute rise in plasma

crEosinophiliaSterile pyuriaPositive Hansel stain (>1% total WBCs are eosinophil)

Active urine sediment with: WBC, RBC, and WBC casts

Normal or mildly increased protein excretion (usually no more than 1g/day)

Renal tubular acidosis

Slide59

Clinical features of AIN

ARF

Hypersensitivity reaction (fever, skin rash, peripheral eosinophilia, and artheralgia)Hypertension and edema are uncommonHematuria, sterile pyuria, leukocyte castsEosinophiluriaMild to moderate proteinuria (< 1gr/day)Electrolyte abnormalities (hyperkalemia, RTA, renal sodium wasting

Slide60

Eosinophiluria

Other conditions associated with EosinophiluriaProstatitisRPGN

Bladder Cancer

Renal

Atheroembolic

disease

Slide61

Diagnostic Studies

CBC

UrinalysisHansel stainRenal ultrasoundGallium scan

Gold standard is renal biopsy.

Indications are:

Uncertainty of diagnosis

Advanced RF

Lack of spontaneous recovery after cessation of offending drug

If

immunosupressive

therapy is considered

Slide62

Treatment of AIN

Discontinue offending agent!!

Most cases improve spontaneouslyPrednisone (1mg/kg/day) for minimum of 1-2 weeksMuch less commonly used

Mycophenylate

mofetil

Cyclosporine

Cyclophosphamide

Slide63

Heme

pigment-induced acute tubular necrosis Myoglobinuria: rhabdomyolysis.Hemoglobinuria: intravascular hemolysis.

Slide64

Heme

pigment-induced acute tubular necrosis

The urine may have a low FENa despite tubular injury. Positive dipstick test for heme pigment without red blood cells on microscopic exam should suggest myoglobinuria or hemoglobinuria.Heme-pigmented granular casts.Plasma is normal color in myoglobinuria and red brown in hemoglobinuria.

Slide65

Crush Syndrome:

Pathophysiology

Resultant effects of derangements due to rhabdomyolysis and reperfusionPotassium  Hyperkalemia  Arrhythmias

Calcium

Hypocalcemia

Arrhythmias

Phosphate

 Hyperphosphatemia Renal damage Myoglobin Myoglobinemia  Renal damageFluid shifts Hypovolemia  Renal failureReperfusion Free radicals  Renal damagePurines  Hyperuricemia  Renal damageHypoxemia Lactic acid  AcidosisThromboplastin Complement system DICCreatinine  Elevated serum levelsSodium  Hyponatremia ARF

Slide66

Crush

Syndrome:outcome

Delay in treatment associated with greater morbidity and mortality50% renal failure at 6 hours100% renal failure at 12 hoursRhabdomyolysis induced renal failure has 40% mortality ARF

Slide67

Entrapped Patient Treatment

Fluid resuscitation before victim extricated1 L NS bolus, followed by 1-1.5 L per hour Limb stabilizationMinimize potential systemic effects of reperfusion Use of tourniquets prior to releaseAlkalinization by giving 1 ampule of sodium bicarbonate (50 mEq) immediately prior to extrication, followed by adding 1 ampule of sodium bicarbonate to each liter of NS infused at 1-1.5 L per hour keep second IV line open without sodium bicarbonate

ARF

Slide68

Hemolysis

Transfusion reactions due to ABO incompatible blood are probably the most frequently encountered hemolytic processes that can lead to acute renal failure.

Severe acute hemolytic episodes in patients with glucose-6-phosphate dehydrogenase deficiency.

Slide69

Slide70

Common Nephrotoxic Agents

Antimicrobial agents

AminoglycosidesAmphotericin BAcyclovirFoscarnetPentamidineChemotherapeutic agentscisplatinmitomycin Cstreptozocin

Vasoactive drugs

NSAIDS

ACE inhibitors

CSA and tacrolimus

Radiocontrast agents

Slide71

Aminoglycoside Nephrotoxicity

Generally presents 1 week after exposure

Non-oliguric Low trough levels do not guard against nephrotoxicityIncidence of ATN10% after 1 week40% after 2 weeks Risk factors for ATNAdvanced age - Superimposed sepsisLiver disease - Hypotension

Slide72

Radiocontrast-Induced

Acute Renal Failure

Induces renal vasoconstriction and direct cytotoxicity via oxygen free radical formationRisk factors:Renal insufficiency - DiabetesAdvanced age - > 125 ml contrastHypotensionUsually non-oliguric ARF; irreversible ARF rare

Slide73

Contrast Induced Nephropathy(CIN)

Assess CIN risk

eGFR <30 – Hospital admission, Nephrology consult, Dialysis planning, renal protectioneGFR 30-59 – Discontinue NSAIDs, IV volume expansion, Intra-arterial: isoosmolar, Intra-venous: iso-osmolar or low osmolar contrast; limit contrast volumeeGFR >60, Discontinue metforminOptimal Volume StatusLow-osmolality contrast mediaF/U Creatinine 24 – 72hr after contrast exposureAdequate IV volume expansion with isotonic crystalloid for 3 – 12hr before the procedure and continue for 6 – 24hr afterward. Oral fluid data is insufficientNo adjunctive medical or mechanical treatment has been proved to be efficacious

Prophylactic hemodialysis and hemofiltration not validated

Slide74

Prevention of Radiocontrast Nephropathy

Intervention

Strength of Evidence

Clarity of Risk-Benefit

Grade of Recommendation

Volume expansion with normal saline

Good

Clear

A: Intervention is always indicated

and acceptable

Volume expansion with sodium bicarbonate

Fair

Clear

B: Intervention may be effective and is acceptable

Iso-osmolar contrast

Fair

Clear

B: Intervention may be effective and is acceptable

Theophylline

Fair

Unclear

C: May be considered; minimal or

no relative impact

N-acetylcysteine

Good

Unclear

C: May be considered; minimal or

no relative impact

Hemofiltration

Fair

Unclear

I: Insufficient evidence to recommend for or against

Fenoldopam

Good

Unclear

D: Not useful

Hemodialysis

Good

Unclear

D: Not useful

Slide75

Acute Renal Failure due to

Intratubular Obstruction

CrystalluriaEthylene glycol: Calcium oxalateTumor lysis: Urate and Calcium phosphate MedicationsAcyclovirMethotrexateSulfonamidesAnti-retroviral agentsMyeloma cast nephropathy

Slide76

Acute Urate Nephropathy

Acute

oliguric renal failure associated with urate levels > 18 mg/dlAssociated with overproduction and excretion of urate in patients undergoing chemotherapy or with a heavy tumor burdenUrine urate/creatinine > 1Prevention: allopurinol 600-900 mg/d + NS (uo

> 2.5 l/d)

Urinary

alkalinization

may worsen calcium phosphate precipitation and NS is as effective as urinary

alkalinization

alone

Early dialysis indicated for

oliguric

ARF to decrease urate burden

Slide77

Renal Disease Associated

with Multiple Myeloma

Myeloma cast nephropathydirect precipitation of casts in tubulesFactors favoring cast precipitation: -affinity of light chains for Tamm-Horsfall protein -high luminal Cl- -volume depletion Plasmapheresis may be beneficial

Hypercalcemic nephropathy

Glomerular lesions (MPGN, Amyloid, Light chain deposition disease)

Slide78

Slide79

AKI: Glomerulonephritis (RPGN)

Immune-Complex Mediated

SLECryoglobulinemic vasculitisHenoch-Schönlein purpuraPost-strep GNDirect Ab attackAnti-GBM diseaseGoodpasture’s syndromePauci-immune vasculitisMicroscopic polyangiitisWegener’s granulomatosisChurg-Strauss syndromeThrombotic MicroangiopathyTTPHUS

Scleroderma renal crisis

Preeclampsia

Malignant hypertension

Slide80

Acute Glomerulonephritis (RPGN)

Accounts for a minority of AKI: ~5%

May have severe morbidity, mortailtyExtra-renal manifestations may be presentPulmonaryDermalGIHematologicHTN may be present, especially in absence of prior HxUA: differentiates from ATN, AINDysmorphic RBC, RBC casts, proteinuria > 0.5gm/24hSerologies, complement activationNeed for specific therapy to reduce Ab critical towards attenuating/reversing AKI

Slide81

Acute Glomerulopathies

RPGN most commonly seen with:

Lupus nephritis (DPGN, class IV)Pauci-immune GN (ANCA associated)Anti-GBM diseaseless commonly: IgA, post-infectiousNephrotic presentations of ARFCollapsing FSGS (HIV nephropathy)Minimal change disease with ATNThrombotic microangiopathies (HUS, TTP, malignant hypertension, scleroderma kidney, pre-eclampsia)

Slide82

Atheroembolic Renal Disease

ARF in patient with erosive atherosclerosis

Often follows aortic manipulation (angiography, surgery, trauma) or anticoagulationPattern is often an acute worsening of renal function due to showering of emboli, followed by more insidious progression over several weeks to months due to ongoing embolization of atheromatous plaquesLivedo reticularisNephritic sediment, eosinophilia, eosinophiluria, low C3Poor prognosis

Slide83

Livedo reticularis

Patient with lupus and anti-phospholipid antibodies with livedo reticularis (manifested by a reddish-cyanotic, reticular pattern of the skin) which has resulted in ulcer formation (arrows). Courtesy of Samuel Moschella, MD.

Slide84

Hollenhorst plaque (cholesterol cyrstal, arrow) in retinal artery

Reproduced with permission from: Digital Reference of Opthalmology, Edward S. Harkness Eye Institute, Columbia University, NY.

Slide85

Hepatorenal

Syndrome

Major CriteriaChronic or acute liver disease with advanced hepatic failure and portal hypertensionLow GFR, as indicated by a serum creatinine >1.5 mg/dL or a creatinine clearance < 40 mL/minAbsence of shock, ongoing bacterial infection, fluid loss, and current or recurrent treatment with nephrotoxic drugs. Absence of gastrointestinal fluid losses (repeated vomiting or intense diarrhea) or renal fluid losses (as indicated by weight loss > 500 gm/d for several days in patients with ascites without peripheral edema or > 100 gm/d in patients with peripheral edema)No sustained improvement in renal function (decrease in serum creatinine to 1.5 mg/dL or less or increase in creatinine clearance to 40 ml/min or more) after withdrawal of diuretics and expansion of plasma volume with 1.5 L of isotonic salineProteinuria < 500 mg/d and ultrasonographic evidence of obstructive uropathy or parenchymal renal disease.

Slide86

Hepatorenal

syndrome

Minor CriteriaUrine volume < 500 mL/dayUrine sodium < 10 mEq/LUrine osmolality > plasma osmolalitySerum sodium concentration < 130 mEq/L

Slide87

Other AKI….

Abdominal Compartment Syndrome

Presence of IAP >20 that is associated with a single or multiple organ system failure. Causes severe oliguric or anuric renal failure. Tx: surgical decompression. Acute Phosphate NephropathyAKI from Nephrocalcinosis after use of oral sodium phosphate (phospho soda) for colonoscopy. Orlistat associated AKIAKI from Oxalate nephropathy due to enhancing oxalate absorption with increased urinary excretion.IVIG associated AKIAKI from osmotic nephrosis from sucrose-containing formulation. Herbal, Home remedies

Arsenal X, Chromium picolinate, Chineses Herb Xi Xin with aristolochic acid; tea from Mouring Cypress, Snake gallbladder, Star fruit (oxalate), Ma Huang (ephedra), Noni Juice

Slide88

Slide89

ARF

Diagnosis BUN and serum crCBC, peripheral smear, serologyUrinalysisUrine electrolytes

U/S kidneys

Serology:

ANA,ANCA, Anti DNA, HBV, HCV, Anti GBM, cryoglobulin, CK, urinary Myoglobulin

Slide90

Ranges of Biochemical Abnormalities in ARF

Daily rise in

Noncatabolic

&

Nonoliguric

Catabolic &

Oliguric

BUN

(mg/dl)

10

20

20 -100

Cr

(mg/dl)

0.5

1

> 2

K

(

mEq

/l)

< 0.5

1

2 (more)

Hco

3

(

mEq

/l)

< 1

> 2

Slide91

Diagnosis

UrinalysisUnremarkable in pre and post renal causes

Differentiates ATN vs. AIN. vs. AGN

Muddy brown casts in ATN

WBC casts in AIN

RBC casts in AGN

Hansel stain for Eosinophils

Slide92

ARF

Diagnosis  Urinary Indices;                          U

Na

   x   P

Cr

         FENa   =     ——————  x  100

                               P

Na

   x   U

Cr

FENa < 1% (Pre-renal state)May be low in selected intrinsic causeContrast nephropathyAcute GNMyoglobin induced ATNFENa > 1% (intrinsic cause of ARF)

Slide93

Urine Indices Used in the

D.Dx

of Prerenal & Intrinsic Azotemia

Diagnostic Index

Prerenal

Azotemia

Intrinsic

Azotemia

Urine SG

>1.018

<1.012

Urine Osmolality

> 500

< 250

BUN / Cr

>20

<10 - 15

Urinary Na conc

.(mEq/l)

<10

>20

Fractional Excretion of Na(%)

UNa×Pcr×100 / PNa×Ucr

<1

>1

Urine sediment

Hyaline casts

Muddy brown granular casts

Slide94

ARF

DiagnosisLaboratory Evaluation:Scr, More reliable marker of GFRFalsely elevated with Cimetidine,….small change reflects large change in GFR

BUN, generally follows Scr increase

Elevation may be independent of GFR

Steroids, GIB, Catabolic state, hypovolemia

BUN/Cr

ratio> 20:1 suggests prerenal cause

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Diagnosis

Indications for Renal Biopsy in AKI:

Acute nephritic syndromeHematuria, cellular casts, proteinuria in setting of new-onset or exacerbation of HTN, rising SCrMay also have serologic (+) i.e. ANA, ANCA, aGBM that tissue dx also provides treatment options and prognosisUnexplained AKIUncertain or multiple competing ddx, of which treatment differs greatly with definitive dx; AIN vs ATN Young pts with AKI often are considered based on long-term renal survival outcomes maximized with definitive dx

ARF

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ARF

-

+

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ARF

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98

Differential diagnosis of acute renal failure

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99

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WBC (Pyuria)

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101

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RBC Cast

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ARF

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104

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106

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Hydronephrosis

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Normal Renal Ultrasound

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Hydronephrosis

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Hydronephrosis

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Prevention of ARF

Strategies that are likely to be effective

Isotonic hydration (IV route)Once-daily dosing of aminoglycosidesUse of lipid formulations of

amphotericin

B

Use of

iso-osmolar

nonionic contrast media

Strategies of unknown efficacy

NAC

TheophyllineLow-dose recombinant ANP (in cardiac surgical patients)Strategies that are not effectiveLoop diureticsDopamine and dopamine receptor agonistsANPsProphylactic hemofiltration

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Can We Prevent AKI?

The best approach to post-ischemic ATN is to

prevent its development. 1.

Identify persons at high risk for AKI, such as:

CKD

Atherosclerosis

DM

Advanced malignancy

Poor nutrition

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Can We Prevent AKI?

2.

Identify settings in which patients are subjected to procedures that may induce post-ischemic ATN:Major surgery particularly:Cardiac surgery

Abdominal aortic aneurysm surgery

Surgery to correct obstructive jaundice

Sepsis

Marked

hypovolemia

Severe pancreatitis

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Can We Prevent AKI?

In patients at increased risk or early in the ischemic phase non-pharmacologic interventions are suggested, including:

Optimizing volume status with IV fluidsMaintenance of adequate hemodynamic status to ensure renal perfusionAvoidance of further injury by removing or decreasing the effect of any nephrotoxins

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Compounds for Prevention of AKI

Diuretics

Loop diureticsMannitolDopamineFenoldopameANPAdenosine AntagonistsIntensive insulin therapy 

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Compounds for Prevention of AKI

Amino acids (Glycine and Alanine)

Antiapoptotic/necrosis agentsMinocyclineGuanosinePifithrin-alphaPoly ADP-ribose polymerase (PARP) inhibitor [5-aminoisoquinolinone (5-AIQ)]

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Compounds for Prevention of AKI

Free radical scavengers

DeferoxaminePyruvateGrowth factors ErythropoiethineHGF IGF-1

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Compounds for Prevention of AKI

Vasodilators

Tezasartan, a dual ET-1 receptor antagonistHeme oxygenases (Hos)Anti-inflammatory drugs Anti-ICAM-1 antibodies and synthetic RGD peptides (arginine-glycine-aspartic acid)StatinsEnhancing tubular cell regeneration by infusion of stem cells

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Compounds for Prevention of AKI

Antioxidants

Other compounds:Neutrophil gelatinase-associated lipocalinIL-6 and C5a antagonistsIL-10 Ghrelin (a compound with a GH releasing effect)

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Diuretics

Diuretics should NOT be administered as prophylaxis for post-ischemic ATN

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Is there a role for Dopamine in Prevention of AKI?

Clinical Outcomes:

No effect on mortalityNo effect on the need for or incidence of RRT

Renal Physiologic Outcomes:

Diuretic effect and increased

cr

clearance on the first day which was not significant on the following days.

Adverse effect:

on the immune, respiratory, and endocrine system.

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Potential risks associated with even low dose dopamine

Tachycardia

Arrhythmias (particularly among cardiac surgery patients)Myocardial ischemiaIntestinal ischemia

(due to precapillary vasoconstriction)

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Is there a role for

Fenoldepam

in prevention of AKI?Dop-1 receptor agonist, lack of Dop-2, and a-1 receptor effect, make it a potentially safer drug than Dopamine!Reduces in hospital mortality and the need for RRT in AKI

Reverses renal hypoperfusion more effectively than renal dose Dopamine

So far so good specially in cardiothoracic ICU patients

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Is there a role for ANP in prevention of AKI

?

ANP is a 28 AA polypeptide synthesized in cardiac atrial muscle.ANP augments GFR by:Afferent arteriolar vasodilatationInhibit the RASInhibits Na transport & lowers oxygen requirements in several nephrone segments ANP analog: Anaritide

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Is there a role for ANP in prevention of AKI

?

ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases hypotension and arrhythmias.

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Adenosine Antagonists (

Theophylline

)Adenosine, in contrast to its general systemic effect as a vasodilator, is a renal arterial vasoconstrictor.Increases afferent arteriolar tone in response to increased distal tubular solute delivery. Acts synergistically with Ang

II to constrict afferent arterioles.

Possible mediator of the

intrarenal

hemodynamic changes that lead to ATN following

radiocontrast

administration.

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Adenosine Antagonists (

Theophylline

) Patients who received theophylline had a smaller increase in serum cr . It remains unclear if theophylline

might be useful preventing contrast nephropathy in some patients.

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Mannitol

Currently no evidence of protective effect

Causes an osmotic diuresis with may benefit fluid balanceIncreasing flow through tubules, preventing obstructionOsmotic action, decreasing endothelial swellingDecreased blood viscosity with increased renal perfusion (???)Free radical scavenging

ARF

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Prevention of ARF

Strategies that are likely to be effective

Isotonic hydration (IV route)Once-daily dosing of aminoglycosidesUse of lipid formulations of

amphotericin

B

Use of

iso-osmolar

nonionic contrast media

Strategies of unknown efficacy

NAC

Theophylline

Low-dose recombinant ANP (in cardiac surgical patients)Strategies that are not effectiveLoop diureticsDopamine and dopamine receptor agonistsANPsProphylactic hemofiltration

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Novel biomarkers

Neutrophil Gelatinase-Assoc. Lipocalin (NGAL)

Levels in blood and urine rise within a few hours after injuryCystatin CAbsorbed by kidney, but not secretedRises one day before CrInterleukin 6&18Produced by caspase-I which is implicted in pathogenesis of ARFKIM-1

Have been shown to predict AKI severity in post-op hearts

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131

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Myths

Frusemide

Theoretically may reduce tubular injuryDue to shutting down Na/K/Cl ATPase Reduces oxygen demandMay help with fluid balance

Reduced energy consumption in the critical outer medulla (by 45% in-vitro)

Wash out tubular debris

But

No clinical evidence

Accumulates in Oliguria

Nephrotoxic and Ototoxic

May actually increase mortality and or need for RRT

ARF

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Myths

Dopamine

Low dose Dopamine (2-3µg/kg/min), known as “renal dose”No effect on mortality or need for Renal replacement therapyARF

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Myths

Vasopressors and AKI

Although Noradrenaline causes vasoconstriction with renal vasculatureNo evidence of worsening AKIBut should be used after adequate volume resuscitationARF

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Myths

Mannitol

Currently no evidence of protective effectCauses an osmotic diuresis with may benefit fluid balanceIncreasing flow through tubules, preventing obstructionOsmotic action, decreasing endothelial swellingDecreased blood viscosity with increased renal perfusion (???)Free radical scavengingARF

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Myths

ANP

Improve renal function and decrease renal insufficiencyTheophyline

Adenosine antagonist – prevents reduction in GFR.

Growth Factors

After ischemic insult, infusion of IGF-I, Epidermal GF,

Hepatocyte

GF improved GFR, diminished morphologic injury, diminished mortality

None of these things are well tested….

ARF

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ARF - Prevention

Maintenance of blood flow

Cardiac output, isovolemia, etcAvoidance of toxinsAminoglycosides, amphoteracin, NSAIDs,…Dose adjustment of drugsEasy on paper….difficult in practiceARF

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Treatment

Prevent it in the First Place!!

Treat / Remove the CauseRestore adequate circulating VolumeRestore adequate blood pressureRestore adequate flow

Control fluid intake

Wait, Patience is a virtue!

Renal replacement therapy

ARF

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ARF - Management

Nutrition management

Initially very catabolicGoals:Adequate caloriesLow proteinLow K and PhosphateDecreased fluid intakeARF

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Indication of dialysis in Acute Renal Failure

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Indications of dialysis in ARF

Severe fluid overload

Refractory hypertensionUncontrollable hyperkalemiaNausea, vomiting, poor appetite, gastritis with hemorrhageProgressive uremic encephalopathy (lethargy, malaise, somnolence, stupor, coma, delirium, asterixis, tremor, seizures)Pericarditis (risk of hemorrhage or tamponade)

bleeding diathesis (epistaxis - GI bleeding and etc..)

attributable to uremia

Severe metabolic acidosis

BUN > 70 – 100 mg/dl

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Dialysis

When initiated?

When uremia can no longer be managed conservatively.Immediately when:Fluid overload unresponsive to diureticsPericarditis Neurologic manifestationsGI manifestations Unresponsive hyperkalemiaUnresponsive acidosis

ARF

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Interventions: Summary

ARF

Prevention

Cause Prevention

Loop Diuretics

Osmotic Diuretics

Ca Channel Blockers

N-

Acetylcysteine

Theophyllines

Treatment

Loop Diuretics

Natriuretic Peptides

Dopamine

Dialysis Mode

Dialysis Dosing

✔ ✔

✔ High dose

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