DrshahramsajjadiehMD nephrologist IDENTIFICATION Azotemia Uremia or Uremic syndrome ARF hours to days RPRFdays to weeks CRF months to years ID: 809605
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Slide1
Slide2Acute kidney injury
Dr.shahram.sajjadieh.MD nephrologist
Slide3IDENTIFICATION
Azotemia
Uremia or Uremic syndrome ARF (hours to days) RPRF(days to weeks) CRF (months to years)
Slide4ARF
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
Slide5Definition 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.
Slide6RIFLE
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
Slide7RIFLE 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
Slide8ARF
8
Median hospital length of stay stratified by single acute organ system dysfunction, including ARF
Slide9Mortality
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
Slide10Non-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.
Slide11Non-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.
Slide12ARF
12
Etiology of ARF
Slide13ARF
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%
Slide14Useful Features That Suggest CRF or ARF
Chronic Hx of:
Nocturia, polyuria, edema or hematuriaPruritus, neuropathy, impotence, other uremic symptomsUnderlying predisposing illness (DM, HTN)
Slide15Useful Features That Suggest CRF or ARF (cont.)
Objective Findings:
Bilateral Small KidneysRenal OsteoDystrophyBand keratopathyCarbamylated Hemoglobine
Slide16Useful Features That Suggest CRF or ARF (cont.)
Less reliable:
AnemiaHypocalcemiaHyperphosphatemia
Slide17Differentiation 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
Slide18Epidemiology
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%
Slide19Clinical Approach to Acute Renal Failure
Slide20AKI: 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
Slide21BUN/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
Slide22ATN vs. Prerenal Azotemia
Indices Prerenal ATN UNa < 20 > 40 FeNa < 1% > 1% U/PCreat > 40 < 20
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
Slide24Urinalysis 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
Slide25Urinary 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
Slide26ARF
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
Slide27ATAPOUR
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.
Slide29Syndromes of Renal Hypoperfusion
Pre renal A.
ACN
ATN
Intermediate syndrome
Slide30Syndromes 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
Slide31ARF
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)
Slide32Conditions 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
Slide33Slide34ARF
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,…
Slide35Course of Ischemic ATN
Prerenal Azotemia
ATNInitiationExtensionMaintenanceRecoveryARF
Slide36Phases of Ischemic Epithelial Tubular Injury
Time
GFR
Pre-renal
Initiation
Extension
Maintenance
Recovery
Slide37ATN -
Pathophysiology
Initiation (hours to days) GFR due to: Renal blood flowObstruction of tubules by castsBack leak of filterate
ARF
Slide38ATN -
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
Slide39ATN - 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
Slide40ATN -
Pathophysiology
4. RecoveryTubular epithelial cell repair and regeneration gradual return of GFR toward premorbid levelsARF
Slide41Slide42Urine 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
Slide43ATN and Mortality
Rising RIFLE class associated with increasing mortality
Patients who are treated with RRT still have a mortality of 50-60%ARF
Slide44Risk Factors for Ischemic Tubular Injury
Volume depletion
AminoglycosidesRadiocontrastNSAIDs, Cox-2 inhibitorsSepsisRhabdomyolysisPreexisting renal diseaseHTNDiabetes mellitusAge > 50
Cirrhosis
Slide45ARF
Slide46ARF
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,…
Slide47Slide48Sepsis and AKI
Sepsis accounts for nearly 50% of all causes of AKI
Combination of FactorsImmunologicalToxicInflammatoryEffect renal microvasculature and Tubular cellsARF
Slide49Tubulointerstitial 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
Slide50Acute Interstitial Nephritis
AIN is a clinicopathologic syndrome of:
ARFAssociated with interstitial edema and cellular infiltrateEtiologyIdiopathic Secondary
Slide51Acute Interstitial Nephritis
10-20% of pts with ARF who have had a renal biopsy have AIN
Slide52Acute 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,…
Slide53Acute Interstitial Nephritis-Etiology
Allergic/Drug induced
AutoimmuneSarcoid ,SLE ,Sjogren’s ToxinsChinese herb nephropathy Heavy metalsLight chain cast nephropathyInfiltrativeLeukemia ,LymphomaInfections (Legionella, CMV, HIV, Toxoplasma)
Slide54Acute 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)
Slide55Acute Kidney Injury: AIN causes
DRUGS
ACEIAllopurinolCephalosporinsCimetidineFluoroquinolonesLoop diueticsNSAIDSPCNPhenytoinRifampinSulfonamidesTegretolThiazidesINFECTIONBacterialAgents causing pyelonephritisLegionella
Brucella
Yersinia
Viral
Hantavirus
HIV
CMV,EBV,HSV
Slide56Pathophysiology
– 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
Slide57NSAID 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
Slide58Laboratory 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
Slide59Clinical 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
Slide60Eosinophiluria
Other conditions associated with EosinophiluriaProstatitisRPGN
Bladder Cancer
Renal
Atheroembolic
disease
Slide61Diagnostic 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
Slide62Treatment 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
Slide63Heme
pigment-induced acute tubular necrosis Myoglobinuria: rhabdomyolysis.Hemoglobinuria: intravascular hemolysis.
Slide64Heme
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.
Slide65Crush 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
Slide66Crush
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
Slide67Entrapped 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
Slide68Hemolysis
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.
Slide69Slide70Common Nephrotoxic Agents
Antimicrobial agents
AminoglycosidesAmphotericin BAcyclovirFoscarnetPentamidineChemotherapeutic agentscisplatinmitomycin Cstreptozocin
Vasoactive drugs
NSAIDS
ACE inhibitors
CSA and tacrolimus
Radiocontrast agents
Slide71Aminoglycoside 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
Slide72Radiocontrast-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
Slide73Contrast 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
Slide74Prevention 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
Slide75Acute Renal Failure due to
Intratubular Obstruction
CrystalluriaEthylene glycol: Calcium oxalateTumor lysis: Urate and Calcium phosphate MedicationsAcyclovirMethotrexateSulfonamidesAnti-retroviral agentsMyeloma cast nephropathy
Slide76Acute 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
Slide77Renal 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)
Slide78Slide79AKI: 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
Slide80Acute 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
Slide81Acute 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)
Slide82Atheroembolic 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
Slide83Livedo 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.
Slide84Hollenhorst plaque (cholesterol cyrstal, arrow) in retinal artery
Reproduced with permission from: Digital Reference of Opthalmology, Edward S. Harkness Eye Institute, Columbia University, NY.
Slide85Hepatorenal
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.
Slide86Hepatorenal
syndrome
Minor CriteriaUrine volume < 500 mL/dayUrine sodium < 10 mEq/LUrine osmolality > plasma osmolalitySerum sodium concentration < 130 mEq/L
Slide87Other 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
Slide88Slide89ARF
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
Slide90Ranges 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
Slide91Diagnosis
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
Slide92ARF
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)
Slide93Urine 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
Slide94ARF
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
Slide95Diagnosis
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
Slide96ARF
-
+
Slide97ARF
Slide9898
Differential diagnosis of acute renal failure
Slide9999
Slide100WBC (Pyuria)
Slide101101
Slide102RBC Cast
Slide103ARF
Slide104104
Slide105Slide106106
Slide107Hydronephrosis
Slide108Normal Renal Ultrasound
Slide109Hydronephrosis
Slide110Hydronephrosis
Slide111Prevention 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
Slide112Can 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
Slide113Can 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
Slide114Can 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
Slide115Compounds for Prevention of AKI
Diuretics
Loop diureticsMannitolDopamineFenoldopameANPAdenosine AntagonistsIntensive insulin therapy
Slide116Compounds for Prevention of AKI
Amino acids (Glycine and Alanine)
Antiapoptotic/necrosis agentsMinocyclineGuanosinePifithrin-alphaPoly ADP-ribose polymerase (PARP) inhibitor [5-aminoisoquinolinone (5-AIQ)]
Slide117Compounds for Prevention of AKI
Free radical scavengers
DeferoxaminePyruvateGrowth factors ErythropoiethineHGF IGF-1
Slide118Compounds 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
Slide119Compounds for Prevention of AKI
Antioxidants
Other compounds:Neutrophil gelatinase-associated lipocalinIL-6 and C5a antagonistsIL-10 Ghrelin (a compound with a GH releasing effect)
Slide120Diuretics
Diuretics should NOT be administered as prophylaxis for post-ischemic ATN
Slide121Is 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.
Slide122Potential risks associated with even low dose dopamine
Tachycardia
Arrhythmias (particularly among cardiac surgery patients)Myocardial ischemiaIntestinal ischemia
(due to precapillary vasoconstriction)
Slide123Is 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
Slide124Is 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
Slide125Is 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.
Slide126Adenosine 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.
Slide127Adenosine 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.
Slide128Mannitol
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
Slide129Prevention 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
Slide130Novel 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
Slide131131
Slide132Myths
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
Slide133Myths
Dopamine
Low dose Dopamine (2-3µg/kg/min), known as “renal dose”No effect on mortality or need for Renal replacement therapyARF
Slide134Myths
Vasopressors and AKI
Although Noradrenaline causes vasoconstriction with renal vasculatureNo evidence of worsening AKIBut should be used after adequate volume resuscitationARF
Slide135Myths
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
Slide136Myths
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
Slide137ARF - Prevention
Maintenance of blood flow
Cardiac output, isovolemia, etcAvoidance of toxinsAminoglycosides, amphoteracin, NSAIDs,…Dose adjustment of drugsEasy on paper….difficult in practiceARF
Slide138Treatment
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
Slide139ARF - Management
Nutrition management
Initially very catabolicGoals:Adequate caloriesLow proteinLow K and PhosphateDecreased fluid intakeARF
Slide140Indication of dialysis in Acute Renal Failure
Slide141Indications 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
Slide142Dialysis
When initiated?
When uremia can no longer be managed conservatively.Immediately when:Fluid overload unresponsive to diureticsPericarditis Neurologic manifestationsGI manifestations Unresponsive hyperkalemiaUnresponsive acidosis
ARF
Slide143Interventions: 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
Slide144